AU2022202534A1

AU2022202534A1 - Modified strains for the production of recombinant silk

Info

Publication number: AU2022202534A1
Application number: AU2022202534A
Authority: AU
Inventors: Matthew Scott Gamboa; Joshua Tyler Kittleson
Original assignee: Bolt Threads Inc
Current assignee: Bolt Threads Inc
Priority date: 2017-10-03
Filing date: 2022-04-19
Publication date: 2022-05-12
Also published as: EP3692054A1; EP3692054A4; WO2019070246A1; JP7246102B2; AU2017434920A1; CN111315763A; JP2021503275A; MX2020003362A; KR102558303B1; AU2017434920B2; KR20200058482A

Abstract

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Description

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TITLE

[0001] Modified Strains for the Production of Recombinant Silk

SEQUENCE LISTING

[0001.1] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on October 25, 2017, is named 37324PCTCRF-sequencelisting.txt and is 388,944 bytes in size.

FIELD OF THE INVENTION

[0002] The present disclosure relates to methods of strain optimization to produce or enhance production of proteins or metabolites from cells. The present disclosure also relates to compositions resulting from those methods. In particular, the disclosure relates to yeast cells selected or genetically engineered to reduce degradation of recombinant proteins expressed by the yeast cells, and to methods of cultivating yeast cells for the production of useful compounds.

BACKGROUND OF THE INVENTION

[0003] The methylotrophic yeast Pichiapastorisis widely used in the production of recombinant proteins. P. pastoris grows to high cell density, provides tightly controlled methanol-inducible trans gene expression and efficiently secretes heterologous proteins in defined media.

[0004] However, during culture of a strain of P. pastoris, recombinantly expressed proteins may be degraded before they can be collected, resulting in a mixture of proteins that includes fragments of recombinantly expressed proteins and a decreased yield of full-length recombinant proteins. What is needed, therefore, are tools and engineered strains to mitigate protein degradation in P. pastoris.

SUMMARY OF THE INVENTION

[0005] In some embodiments, provided herein is a Pichiapastorismicroorganism, in which the activity of a YPS1-1 protease and a YPS1-2 protease has been attenuated or eliminated, wherein said microorganism expresses a recombinant polypeptide.

[0006] In some embodiments, the YPS1-1 protease comprises apolypeptide sequence at least 95% identical to SEQ ID NO: 67. In some embodiments, the YPS1-1 protease comprises SEQ ID NO: 67. In some embodiments, the YPS1-1 protease is encoded by a YPS1-1 gene. In some embodiments, the YPS1-1 gene comprises a polynucleotide sequence at least 95% identical to SEQ ID NO: 1. In some embodiments, the YPS1-1 gene comprises at least 15, 20, 25, 30, 40, or 50 contiguous nucleotides of SEQ ID NO: 1. In some embodiments, the YPS1-1 gene comprises SEQ ID NO: 1. In some embodiments, the YPS1 1 gene is at locus PASchr4_0584 of said microorganism.

[0007] In some embodiments, the YPS1-2 protease comprises apolypeptide sequence at least 95% identical to SEQ ID NO: 68. In some embodiments, the YPS1-2 protease comprises SEQ ID NO: 68. In some embodiments, the YPS1-2 protease is encoded by a YPS1-2 gene. In some embodiments, the YPS1-2 gene comprises a polynucleotide sequence at least 95% identical to SEQ ID NO: 2. In some embodiments, the YPS1-2 gene comprises at least 15, 20, 25, 30, 40, or 50 contiguous nucleotides of SEQ ID NO: 2. In some embodiments, the YPS1-2 gene comprises SEQ ID NO: 2. In some embodiments, the YPS1 2 gene is at locus PASchr3_1157 of said microorganism.

[0008] In some embodiments, the YPS1-1 gene or said YPS1-2 gene, or both, has been mutated or knocked out.

[0009] In some embodiments, the microorganism expresses a recombinant protein. In some embodiments, the recombinant protein comprises at least one block polypeptide sequence from a silk protein. In some embodiments, the recombinant protein comprises a silk-like polypeptide. In some embodiments, the silk-like polypeptide comprises one or more repeat sequences {GGY-[GPG-Xi]ni-GPS-(A)n 2 }n3 (SEQ ID NO: 514), wherein Xi = SGGQQ (SEQ ID NO: 515) or GAGQQ (SEQ ID NO: 516) or GQGPY (SEQ ID NO: 517) or AGQQ (SEQ ID NO: 518) or SQ; nI is from 4 to 8; n2 is from 6 to 20; and n3 is from 2 to 20. In some embodiments, the silk-like polypeptide comprises comprises a polypeptide sequence encoded by SEQ ID NO: 462.

[0010] In some embodiments, the activity of one or more additional proteases in the microorganism has been attenuated or eliminated. In some embodiments, the one or more additional proteases comprises YPS1-5, MCK7, or YPS1-3.

[0011] In some embodiments, the YPS1-5 gene is at locus PASchr3_0688 of said microorganism.

[0012] In some embodiments, the MCK7 protease is encoded by a MCK7 gene comprising a polynucleotide sequence at least 95% identical to SEQ ID NO: 7. In some embodiments, the MCK7 gene comprises at least 15, 20, 25, 30, 40, or 50 contiguous nucleotides of SEQ

ID NO: 7. In some embodiments, the MCK7 gene comprises SEQ ID NO: 7. In some embodiments, the MCK7 gene is at locus PASchrl-1_0379 of said microorganism.

[0013] In some embodiments, the YPS1-3 protease is encoded by a YPS1-3 gene comprising a polynucleotide sequence at least 95% identical to SEQ ID NO: 3. In some embodiments, the YPS1-3 gene comprises at least 15, 20, 25, 30, 40, or 50 contiguous nucleotides of SEQ ID NO: 3. In some embodiments, the YPS1-3 gene comprises SEQ ID NO: 3. In some embodiments, the YPS1-3 gene is at locus PASchr3_0299 of said microorganism.

[0014] In some embodiments, the one or more additional proteases comprise a polypeptide sequence at least 95% identical to a polypeptide sequence selected from the group consisting of: SEQ ID NO: 68 - 130. In some embodiments, the one or more additional proteases comprise a polypeptide sequence selected from the group consisting of: SEQ ID NO: 68 130. In some embodiments, the one or more additional proteases are encoded by a polynucleotide sequence at least 95% identical to a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 3 - 66. In some embodiments, the one or more additional proteases are encoded by a polynucleotide sequence comprising at least 15, 20, 25, , 40, or 50 contiguous nucleotides of a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 3 - 66.

[0015] In some embodiments, the microorganism comprises a 3X, 4X or 5X protease knockout.

[0016] Also provided herein, according to some embodiments of the invention, is aPichia pastoris engineered microorganism comprising YPS1-1 and YPS1-2 activity reduced by a mutation or deletion of the YPS1-1 gene comprising SEQ ID NO: 1 and the YPS1-2 gene comprising SEQ ID NO: 2, wherein said microorganism further comprises a recombinantly expressed protein comprising a polypeptide sequence encoded by SEQ ID NO: 462.

[0017] In some embodiments, also provided herein is cell culture comprising a protease mitigated microorganism as described herein.

[0018] Also provided herein, according to some embodiments, is a cell culture comprising a microorganism whose YPS1-1 and YPS1-2 activity has been attenuated or eliminated as described herein, wherein the microorganism recombinantly expresses a protein, wherein said recombinantly expressed protein is less degraded than a cell culture comprising an otherwise identical Picha pastoris microorganism whose YPS1-1 and YPS1-2 activity has not been attenuated or eliminated.

[0019] In some embodiments, provided herein is a method of producing a recombinant protein with a reduced degradation, comprising: culturing whose YPS1-1 and YPS1-2 activity has been attenuated or eliminated as described herein in a culture medium under conditions suitable for expression of the recombinantly expressed protein; and isolating the recombinant protein from the microorganism or the culture medium.

[0020] In some embodiments, the recombinant protein is secreted from said microorganism, and wherein isolating said recombinant protein comprises collecting a culture medium comprising said secreted recombinant protein. In some embodiments, the recombinant protein has a decreased level of degradation as compared to said recombinant protein produced by an otherwise identical microorganism wherein said YPS1-1 and said YPS1-2 protease activity has not been attenuated or eliminated.

[0021] Also provided herein is a method of modifying Pichiapastoristo reduce the degradation of a recombinantly expressed protein, comprising knocking out or mutating a gene encoding a YPS1-1 protein and a YPS1-2 protein. In some embodiments, the method of modifying Pichiapastoristo reduce the degradation of a recombinantly expressed protein further comprises knocking out or mutating one or more additional genes encoding a YPS1-3 protein, a YPS1-5 protein, or an MCK7 protein. In some embodiments, the method of modifying Pichiapastoristo reduce the degradation of a recombinantly expressed protein further comprises knocking out one or more genes encoding a protein comprising a polypeptide selected from the group consisting of SEQ ID NO: 68-130.

[0022] In some embodiments, the recombinantly expressed protein comprises a polyA sequence comprising at least at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 contiguous alanine residues (SEQ ID NO: 519). In some embodiments, the recombinantly expressed protein comprises a silk-like polypeptide. In some embodiments, the silk-like polypeptide comprises one or more repeat sequences {GGY-[GPG-Xi]ni-GPS-(A)n 2 }3 (SEQ ID NO: 514), wherein Xi = SGGQQ (SEQ ID NO: 515) or GAGQQ (SEQ ID NO: 516) or GQGPY (SEQ ID NO: 517) or AGQQ (SEQ ID NO: 518) or SQ; nI is from 4 to 8; n2 is from 6 to 20; and n3 is from 2 to 20. In some embodiments, the recombinantly expressed protein comprises a polypeptide sequence encoded by SEQ ID NO: 462.

BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The foregoing and other objects, features and advantages will be apparent from the following description of particular embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead placed upon illustrating the principles of various embodiments of the invention.

[0024] Figure 1 is a plasmid map for KU 70 deletion with a zeocin resistance marker.

[0025] Figure 2 is a plasmid map of a plasmid comprising a nourseothricin marker used with homology arms for targeted protease gene deletion.

[0026] Figure 3A and Figure 3B are cassettes for protease knockout with homology arms targeting the desired protease gene flanking a nourseothricin resistance marker.

[0027] Figure 4 is a representative western blot of protein isolated from single KO strains to show protein degradation from these strains.

[0028] Figure 5 is a representative western blot of protein isolated from double KO strains to show protein degradation from these strains.

[0029] Figure 6 is a representative western blot of protein isolated from 2X, 3X, 4X, and X protease KO strains subcultured in BMGY or YPD to show protein degradation in these strains.

DETAILED DESCRIPTION

[0030] The details of various embodiments of the invention are set forth in the description below. Other features, objects, and advantages of the invention will be apparent from the description and the drawings, and from the claims.

Definitions

[0031] Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular. The terms "a" and "an" includes plural references unless the context dictates otherwise. Generally, nomenclatures used in connection with, and techniques of, biochemistry, enzymology, molecular and cellular biology, microbiology, genetics and protein and nucleic acid chemistry and hybridization described herein are those well-known and commonly used in the art.

[0032] The following terms, unless otherwise indicated, shall be understood to have the following meanings:

[0033] The term "polynucleotide" or "nucleic acid molecule" refers to a polymeric form of nucleotides of at least 10 bases in length. The term includes DNA molecules (e.g., cDNA or genomic or synthetic DNA) and RNA molecules (e.g., mRNA or synthetic RNA), as well as analogs of DNA or RNA containing non-natural nucleotide analogs, non-native intemucleoside bonds, or both. The nucleic acid can be in any topological conformation. For instance, the nucleic acid can be single-stranded, double-stranded, triple-stranded, quadruplexed, partially double-stranded, branched, hairpinned, circular, or in a padlocked conformation.

[0034] Unless otherwise indicated, and as an example for all sequences described herein under the general format "SEQ ID NO:", "nucleic acid comprising SEQ ID NO:1" refers to a nucleic acid, at least a portion of which has either (i) the sequence of SEQ ID NO:1, or (ii) a sequence complementary to SEQ ID NO:1. The choice between the two is dictated by the context. For instance, if the nucleic acid is used as a probe, the choice between the two is dictated by the requirement that the probe be complementary to the desired target.

[0035] An "isolated" RNA, DNA or a mixed polymer is one which is substantially separated from other cellular components that naturally accompany the native polynucleotide in its natural host cell, e.g., ribosomes, polymerases and genomic sequences with which it is naturally associated.

[0036] An "isolated" organic molecule (e.g., a silk protein) is one which is substantially separated from the cellular components (membrane lipids, chromosomes, proteins) of the host cell from which it originated, or from the medium in which the host cell was cultured. The term does not require that the biomolecule has been separated from all other chemicals, although certain isolated biomolecules may be purified to near homogeneity.

[0037] The term "recombinant" refers to a biomolecule, e.g., a gene or protein, that (1) has been removed from its naturally occurring environment, (2) is not associated with all or a portion of a polynucleotide in which the gene is found in nature, (3) is operatively linked to a polynucleotide which it is not linked to in nature, or (4) does not occur in nature. The term "recombinant" can be used in reference to cloned DNA isolates, chemically synthesized

polynucleotide analogs, or polynucleotide analogs that are biologically synthesized by heterologous systems, as well as proteins and/or mRNAs encoded by such nucleic acids.

[0038] An endogenous nucleic acid sequence in the genome of an organism (or the encoded protein product of that sequence) is deemed "recombinant" herein if a heterologous sequence is placed adjacent to the endogenous nucleic acid sequence, such that the expression of this endogenous nucleic acid sequence is altered. In this context, a heterologous sequence is a sequence that is not naturally adjacent to the endogenous nucleic acid sequence, whether or not the heterologous sequence is itself endogenous (originating from the same host cell or progeny thereof) or exogenous (originating from a different host cell or progeny thereof). By way of example, a promoter sequence can be substituted (e.g., by homologous recombination) for the native promoter of a gene in the genome of a host cell, such that this gene has an altered expression pattern. This gene would now become "recombinant" because it is separated from at least some of the sequences that naturally flank it.

[0039] A nucleic acid is also considered "recombinant" if it contains any modifications that do not naturally occur to the corresponding nucleic acid in a genome. For instance, an endogenous coding sequence is considered "recombinant" if it contains an insertion, deletion or a point mutation introduced artificially, e.g., by human intervention. A "recombinant nucleic acid" also includes a nucleic acid integrated into a host cell chromosome at a heterologous site and a nucleic acid construct present as an episome.

[0040] As used herein, the phrase "degenerate variant" of a reference nucleic acid sequence encompasses nucleic acid sequences that can be translated, according to the standard genetic code, to provide an amino acid sequence identical to that translated from the reference nucleic acid sequence. The term "degenerate oligonucleotide" or "degenerate primer" is used to signify an oligonucleotide capable of hybridizing with target nucleic acid sequences that are not necessarily identical in sequence but that are homologous to one another within one or more particular segments.

[0041] The term "percent sequence identity" or "identical" in the context of nucleic acid sequences refers to the residues in the two sequences which are the same when aligned for maximum correspondence. The length of sequence identity comparison may be over a stretch of at least about nine nucleotides, usually at least about 20 nucleotides, more usually at least about 24 nucleotides, typically at least about 28 nucleotides, more typically at least about 32 nucleotides, and preferably at least about 36 or more nucleotides. There are a number of different algorithms known in the art which can be used to measure nucleotide sequence identity. For instance, polynucleotide sequences can be compared using FASTA, Gap or Bestfit, which are programs in Wisconsin Package Version 10.0, Genetics Computer Group (GCG), Madison, Wis. FASTA provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences. Pearson, Methods Enzymol. 183:63-98 (1990) (hereby incorporated by reference in its entirety). For instance, percent sequence identity between nucleic acid sequences can be determined using FASTA with its default parameters (a word size of 6 and the NOPAM factor for the scoring matrix) or using Gap with its default parameters as provided in GCG Version 6.1, herein incorporated by reference. Alternatively, sequences can be compared using the computer program, BLAST (Altschul et al., J. Mol. Biol. 215:403-410 (1990); Gish and States, Nature

Genet. 3:266-272 (1993); Madden et al., Meth. Enzymol. 266:131-141 (1996); Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997); Zhang and Madden, Genome Res. 7:649-656 (1997)), especially blastp or tblastn (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)).

[0042] The term "substantial homology" or "substantial similarity," when referring to a nucleic acid or fragment thereof, indicates that, when optimally aligned with appropriate nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 75%, 80%, 85%, preferably at least about 90%, and more preferably at least about 95%, 96%, 97%, 98% or 99% of the nucleotide bases, as measured by any well-known algorithm of sequence identity, such as FASTA, BLAST or Gap, as discussed above.

[0043] Alternatively, substantial homology or similarity exists when a nucleic acid or fragment thereof hybridizes to another nucleic acid, to a strand of another nucleic acid, or to the complementary strand thereof, under stringent hybridization conditions. "Stringent hybridization conditions" and "stringent wash conditions" in the context of nucleic acid hybridization experiments depend upon a number of different physical parameters. Nucleic acid hybridization will be affected by such conditions as salt concentration, temperature, solvents, the base composition of the hybridizing species, length of the complementary regions, and the number of nucleotide base mismatches between the hybridizing nucleic acids, as will be readily appreciated by those skilled in the art. One having ordinary skill in the art knows how to vary these parameters to achieve a particular stringency of hybridization.

[0044] In general, "stringent hybridization" is performed at about 25°C below the thermal melting point (Tm) for the specific DNA hybrid under a particular set of conditions. "Stringent washing" is performed at temperatures about 5°C lower than the Tm for the specific DNA hybrid under a particular set of conditions. The Tm is the temperature at which % of the target sequence hybridizes to a perfectly matched probe. See Sambrook et al., Molecular Cloning: A Laboratory Manual, 2d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989), page 9.51, hereby incorporated by reference. For purposes herein, "stringent conditions" are defined for solution phase hybridization as aqueous hybridization (i.e., free of formamide) in 6xSSC (where 20xSSC contains 3.0 M NaCl and 0.3 M sodium citrate), 1% SDS at 65°C for 8-12 hours, followed by two washes in 0.2xSSC, 0.1% SDS at 65°C for 20 minutes. It will be appreciated by the skilled worker that hybridization at 65 0C will occur at different rates depending on a number of factors including the length and percent identity of the sequences which are hybridizing.

[0045] The nucleic acids (also referred to as polynucleotides) of this present invention may include both sense and antisense strands of RNA, cDNA, genomic DNA, and synthetic forms and mixed polymers of the above. They may be modified chemically or biochemically or may contain non-natural or derivatized nucleotide bases, as will be readily appreciated by those of skill in the art. Such modifications include, for example, labels, methylation, substitution of one or more of the naturally occurring nucleotides with an analog, intemucleotide modifications such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoramidates, carbamates, etc.), charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), pendent moieties (e.g., polypeptides), intercalators (e.g., acridine, psoralen, etc.), chelators, alkylators, and modified linkages (e.g., alpha anomeric nucleic acids, etc.) Also included are synthetic molecules that mimic polynucleotides in their ability to bind to a designated sequence via hydrogen bonding and other chemical interactions. Such molecules are known in the art and include, for example, those in which peptide linkages substitute for phosphate linkages in the backbone of the molecule. Other modifications can include, for example, analogs in which the ribose ring contains a bridging moiety or other structure such as the modifications found in "locked" nucleic acids.

[0046] The term "mutated" when applied to nucleic acid sequences means that nucleotides in a nucleic acid sequence may be inserted, deleted or changed compared to a reference nucleic acid sequence. A single alteration may be made at a locus (a point mutation) or multiple nucleotides may be inserted, deleted or changed at a single locus. In addition, one or more alterations may be made at any number of loci within a nucleic acid sequence. A nucleic acid sequence may be mutated by any method known in the art including but not limited to mutagenesis techniques such as "error-prone PCR" (a process for performing PCR under conditions where the copying fidelity of the DNA polymerase is low, such that a high rate of point mutations is obtained along the entire length of the PCR product; see, e.g., Leung et al., Technique, 1:11-15 (1989) and Caldwell and Joyce, PCR Methods Applic. 2:28 33 (1992)); and "oligonucleotide-directed mutagenesis" (a process which enables the generation of site-specific mutations in any cloned DNA segment of interest; see, e.g., Reidhaar-Olson and Sauer, Science 241:53-57 (1988)).

[0047] The term "attenuate" as used herein generally refers to a functional deletion, including a mutation, partial or complete deletion, insertion, or other variation made to a gene sequence or a sequence controlling the transcription of a gene sequence, which reduces or inhibits production of the gene product, or renders the gene product non-functional. In some instances a functional deletion is described as a knockout mutation. Attenuation also includes amino acid sequence changes by altering the nucleic acid sequence, placing the gene under the control of a less active promoter, down-regulation, expressing interfering RNA, ribozymes or antisense sequences that target the gene of interest, or through any other technique known in the art. In one example, the sensitivity of a particular enzyme to feedback inhibition or inhibition caused by a composition that is not a product or a reactant (non-pathway specific feedback) is lessened such that the enzyme activity is not impacted by the presence of a compound. In other instances, an enzyme that has been altered to be less active can be referred to as attenuated.

[0048] The term "deletion" as used herein refers to the removal of one or more nucleotides from a nucleic acid molecule or one or more amino acids from a protein, the regions on either side being joined together.

[0049] The term "knock-out" as used herein is intended to refer to a gene whose level of expression or activity has been reduced to zero. In some examples, a gene is knocked-out via deletion of some or all of its coding sequence. In other examples, a gene is knocked-out via introduction of one or more nucleotides into its open reading frame, which results in translation of a non-sense or otherwise non-functional protein product.

[0050] The term "vector" as used herein is intended to refer to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid," which generally refers to a circular double stranded DNA loop into which additional DNA segments may be ligated, but also includes linear double-stranded molecules such as those resulting from amplification by the polymerase chain reaction (PCR) or from treatment of a circular plasmid with a restriction enzyme. Other vectors include cosmids, bacterial artificial chromosomes (BAC) and yeast artificial chromosomes (YAC). Another type of vector is a viral vector, wherein additional DNA segments may be ligated into the viral genome (discussed in more detail below). Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., vectors having an origin of replication which functions in the host cell). Other vectors can be integrated into the genome of a host cell upon introduction into the host cell, and are thereby replicated along with the host genome. Moreover, certain preferred vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as "recombinant expression vectors" (or simply "expression vectors").

[0051] "Operatively linked" or "operably linked" expression control sequences refers to a linkage in which the expression control sequence is contiguous with the gene of interest to control the gene of interest, as well as expression control sequences that act in trans or at a distance to control the gene of interest.

[0052] The term "expression control sequence" refers to polynucleotide sequences which are necessary to affect the expression of coding sequences to which they are operatively linked. Expression control sequences are sequences which control the transcription, post transcriptional events and translation of nucleic acid sequences. Expression control sequences include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (e.g., ribosome binding sites); sequences that enhance protein stability; and when desired, sequences that enhance protein secretion. The nature of such control sequences differs depending upon the host organism; in prokaryotes, such control sequences generally include promoter, ribosomal binding site, and transcription termination sequence. The term "control sequences" is intended to include, at a minimum, all components whose presence is essential for expression, and can also include additional components whose presence is advantageous, for example, leader sequences and fusion partner sequences.

[0053] The term "regulatory element" refers to any element which affects transcription or translation of a nucleic acid molecule. These include, by way of example but not limitation: regulatory proteins (e.g., transcription factors), chaperones, signaling proteins, RNAi molecules, antisense RNA molecules, microRNAs and RNA aptamers. Regulatory elements may be endogenous to the host organism. Regulatory elements may also be exogenous to the host organism. Regulatory elements may be synthetically generated regulatory elements.

[0054] The term "promoter," "promoter element," or "promoter sequence" as used herein, refers to a DNA sequence which when ligated to a nucleotide sequence of interest is capable of controlling the transcription of the nucleotide sequence of interest into mRNA. A promoter is typically, though not necessarily, located 5'(i.e., upstream) of a nucleotide sequence of interest whose transcription into mRNA it controls, and provides a site for specific binding by RNA polymerase and other transcription factors for initiation of transcription. Promoters may be endogenous to the host organism. Promoters may also be exogenous to the host organism. Promoters may be synthetically generated regulatory elements.

[0055] Promoters useful for expressing the recombinant genes described herein include both constitutive and inducible/repressible promoters. Where multiple recombinant genes are expressed in an engineered organism of the invention, the different genes can be controlled by different promoters or by identical promoters in separate operons, or the expression of two or more genes may be controlled by a single promoter as part of an operon.

[0056] The term "recombinant host cell" (or simply "host cell"), as used herein, is intended to refer to a cell into which a recombinant vector has been introduced. It should be understood that such terms are intended to refer not only to the particular subject cell but to the progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term "host cell" as used herein. A recombinant host cell may be an isolated cell or cell line grown in culture or may be a cell which resides in a living tissue or organism.

[0057] The term "peptide" as used herein refers to a short polypeptide, e.g., one that is typically less than about 50 amino acids long and more typically less than about 30 amino acids long. The term as used herein encompasses analogs and mimetics that mimic structural and thus biological function.

[0058] The term "polypeptide" encompasses both naturally-occurring and non-naturally occurring proteins, and fragments, mutants, derivatives and analogs thereof. A polypeptide may be monomeric or polymeric. Further, a polypeptide may comprise a number of different domains each of which has one or more distinct activities.

[0059] The term "isolated protein" or "isolated polypeptide" is a protein or polypeptide that by virtue of its origin or source of derivation (1) is not associated with naturally associated components that accompany it in its native state, (2) exists in a purity not found in nature, where purity can be adjudged with respect to the presence of other cellular material (e.g., is free of other proteins from the same species) (3) is expressed by a cell from a different species, or (4) does not occur in nature (e.g., it is a fragment of a polypeptide found in nature or it includes amino acid analogs or derivatives not found in nature or linkages other than standard peptide bonds). Thus, a polypeptide that is chemically synthesized or synthesized in a cellular system different from the cell from which it naturally originates will be "isolated" from its naturally associated components. A polypeptide or protein may also be rendered substantially free of naturally associated components by isolation, using protein purification techniques well known in the art. As thus defined, "isolated" does not necessarily require that the protein, polypeptide, peptide or oligopeptide so described has been physically removed from its native environment.

[0060] The term "polypeptide fragment" refers to a polypeptide that has a deletion, e.g., an amino-terminal and/or carboxy-terminal deletion compared to a full-length polypeptide. In a preferred embodiment, the polypeptide fragment is a contiguous sequence in which the amino acid sequence of the fragment is identical to the corresponding positions in the naturally-occurring sequence. Fragments typically are at least 5, 6, 7, 8, 9 or 10 amino acids long, preferably at least 12, 14, 16 or 18 amino acids long, more preferably at least 20 amino acids long, more preferably at least 25, 30, 35, 40 or 45, amino acids, even more preferably at least 50 or 60 amino acids long, and even more preferably at least 70 amino acids long.

[0061] A protein has "homology" or is "homologous" to a second protein if the nucleic acid sequence that encodes the protein has a similar sequence to the nucleic acid sequence that encodes the second protein. Alternatively, a protein has homology to a second protein if the two proteins have "similar" amino acid sequences. (Thus, the term "homologous proteins" is defined to mean that the two proteins have similar amino acid sequences.) As used herein, homology between two regions of amino acid sequence (especially with respect to predicted structural similarities) is interpreted as implying similarity in function.

[0062] When "homologous" is used in reference to proteins or peptides, it is recognized that residue positions that are not identical often differ by conservative amino acid substitutions. A "conservative amino acid substitution" is one in which an amino acid residue is substituted by another amino acid residue having a side chain (R group) with similar chemical properties (e.g., charge or hydrophobicity). In general, a conservative amino acid substitution will not substantially change the functional properties of a protein. In cases where two or more amino acid sequences differ from each other by conservative substitutions, the percent sequence identity or degree of homology may be adjusted upwards to correct for the conservative nature of the substitution. Means for making this adjustment are well known to those of skill in the art. See, e.g., Pearson, 1994, Methods Mol. Biol. 24:307-31 and 25:365-89 (herein incorporated by reference).

[0063] The twenty conventional amino acids and their abbreviations follow conventional usage. See Immunology-A Synthesis (Golub and Gren eds., Sinauer Associates, Sunderland, Mass., 2"d ed. 1991), which is incorporated herein by reference. Stereoisomers (e.g., D-amino acids) of the twenty conventional amino acids, unnatural amino acids such as a-, a disubstituted amino acids, N-alkyl amino acids, and other unconventional amino acids may also be suitable components for polypeptides of the present invention. Examples of unconventional amino acids include: 4-hydroxyproline, y-carboxyglutamate, c-N,N,N trimethyllysine, c-N-acetyllysine, 0-phosphoserine, N-acetylserine, N-formylmethionine, 3 methylhistidine, 5-hydroxylysine, N-methylarginine, and other similar amino acids and imino acids (e.g., 4-hydroxyproline). In the polypeptide notation used herein, the left-hand end corresponds to the amino terminal end and the right-hand end corresponds to the carboxy terminal end, in accordance with standard usage and convention.

[0064] The following six groups each contain amino acids that are conservative substitutions for one another: 1) Serine (S), Threonine (T); 2) Aspartic Acid (D), Glutamic Acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Alanine (A), Valine (V), and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W).

[0065] Sequence homology for polypeptides, which is sometimes also referred to as percent sequence identity, is typically measured using sequence analysis software. See, e.g., the Sequence Analysis Software Package of the Genetics Computer Group (GCG), University of Wisconsin Biotechnology Center, 910 University Avenue, Madison, Wis. 53705. Protein analysis software matches similar sequences using a measure of homology assigned to various substitutions, deletions and other modifications, including conservative amino acid substitutions. For instance, GCG contains programs such as "Gap" and "Bestfit" which can be used with default parameters to determine sequence homology or sequence identity between closely related polypeptides, such as homologous polypeptides from different species of organisms or between a wild-type protein and a mutein thereof. See, e.g., GCG Version 6.1.

[0066] A useful algorithm when comparing a particular polypeptide sequence to a database containing a large number of sequences from different organisms is the computer program BLAST (Altschul et al., J Mol. Biol. 215:403-410 (1990); Gish and States, Nature Genet. 3:266-272 (1993); Madden et al., Meth. Enzymol. 266:131-141 (1996); Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997); Zhang and Madden, Genome Res. 7:649-656 (1997)), especially blastp or tblastn (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)).

[0067] Preferred parameters for BLASTp are: Expectation value: 10 (default); Filter: seg (default); Cost to open a gap: 11 (default); Cost to extend a gap: 1 (default); Max. alignments: 100 (default); Word size: 11 (default); No. of descriptions: 100 (default); Penalty Matrix: BLOWSUM62.

[0068] Preferred parameters for BLASTp are: Expectation value: 10 (default); Filter: seg (default); Cost to open a gap: 11 (default); Cost to extend a gap: 1 (default); Max. alignments: 100 (default); Word size: 11 (default); No. of descriptions: 100 (default); Penalty Matrix: BLOWSUM62.The length of polypeptide sequences compared for homology will generally be at least about 16 amino acid residues, usually at least about 20 residues, more usually at least about 24 residues, typically at least about 28 residues, and preferably more than about 35 residues. When searching a database containing sequences from a large number of different organisms, it is preferable to compare amino acid sequences. Database searching using amino acid sequences can be measured by algorithms other than blastp known in the art. For instance, polypeptide sequences can be compared using FASTA, a program in GCG Version 6.1. FASTA provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences. Pearson, Methods Enzymol. 183:63-98 (1990) (incorporated by reference herein). For example, percent sequence identity between amino acid sequences can be determined using FASTA with its default parameters (a word size of 2 and the PAM250 scoring matrix), as provided in GCG Version 6.1, herein incorporated by reference.

[0069] Throughout this specification and claims, the word "comprise" or variations such as ''comprises" or'"comprising," will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

[0070] Exemplary methods and materials are described below, although methods and materials similar or equivalent to those described herein can also be used in the practice of the present invention and will be apparent to those of skill in the art. All publications and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. The materials, methods, and examples are illustrative only and not intended to be limiting.

Overview

[0071] Provided herein are recombinant strains and methods of producing recombinant strains to increase production of a full-length desired product in a target cell, e.g., by reducing protease degradation.

[0072] In some embodiments, to attenuate a protease activity in Pichiapastoris, the genes encoding these enzymes are inactivated or mutated to reduce or eliminate activity. This can be done through mutations or insertions into the gene itself of through modification of a gene regulatory element. This can be achieved through standard yeast genetics techniques. Examples of such techniques include gene replacement through double homologous recombination, in which homologous regions flanking the gene to be inactivated are cloned in a vector flanking a selectable maker gene (such as an antibiotic resistance gene or a gene complementing an auxotrophy of the yeast strain).

[0073] Alternatively, the homologous regions can be PCR-amplified and linked through overlapping PCR to the selectable marker gene. Subsequently, such DNA fragments are transformed into Pichiapastoristhrough methods known in the art, e.g., electroporation. Transformants that then grow under selective conditions are analyzed for the gene disruption event through standard techniques, e.g. PCR on genomic DNA or Southern blot. In an alternative experiment, gene inactivation can be achieved through single homologous recombination, in which case, e.g. the 5'end of the gene's ORF is cloned on a promoterless vector also containing a selectable marker gene. Upon linearization of such vector through digestion with a restriction enzyme only cutting the vector in the target-gene homologous fragment, such vector is transformed into Pichiapastoris. Integration at the target gene site is confirmed through PCR on genomic DNA or Southern blot. In this way, a duplication of the gene fragment cloned on the vector is achieved in the genome, resulting in two copies of the target gene locus: a first copy in which the ORF is incomplete, thus resulting in the expression (if at all) of a shortened, inactive protein, and a second copy which has no promoter to drive transcription.

[0074] Alternatively, transposon mutagenesis is used to inactivate the target gene. A library of such mutants can be screened through PCR for insertion events in the target gene.

[0075] The functional phenotype (i.e., deficiencies) of an engineered/knockout strain can be assessed using techniques known in the art. For example, a deficiency of an engineered strain in protease activity can be ascertained using any of a variety of methods known in the art, such as an assay of hydrolytic activity of chromogenic protease substrates, band shifts of substrate proteins for the selected protease, among others.

[0076] Attenuation of a protease activity described herein can be achieved through mechanisms other than a knockout mutation. For example, a desired protease can be attenuated via amino acid sequence changes by altering the nucleic acid sequence, placing the gene under the control of a less active promoter, down-regulation, expressing interfering RNA, ribozymes or antisense sequences that target the gene of interest, or through any other technique known in the art. In preferred strains, the protease activity of proteases encoded at PASchr4_0584 (YPS1-1) and PASchr3_1157 (YPS1-2) (e.g., polypeptides comprising SEQ ID NO: 66 and 67) is attenuated by any of the methods described above. In some aspects, the invention is directed to methylotrophic yeast strains, especially Pichiapastoris strains, wherein a YPS1-1 and a YPS1-2 gene (e.g., as set forth in SEQ ID NO: 1 and SEQ ID NO: 2) have been inactivated. In some embodiments, additional protease encoding genes may also be knocked-out in accordance with the methods provided herein to further reduce protease activity of a desired protein product expressed by the strain.

Production of recombinant strains

[0077] Provided herein are methods of transforming a strain to reduce activity, e.g., using vectors to deliver recombinant genes or to knock-out or otherwise attenuate endogenous genes as desired. These vectors can take the form of a vector backbone containing a replication origin and a selection marker (typically antibiotic resistance, although many other methods are possible), or a linear fragment that enables incorporation into the target cell's chromosome. The vectors should correspond to the organism and insertion method chosen.

[0078] Once the elements of a vector are selected, construction of the vector can be performed in many different ways. In an embodiment, a DNA synthesis service or a method to individually make every vector may be used.

[0079] Once the DNA for each vector (including the additional elements required for insertion and operation) is acquired, it must be assembled. There are many possible assembly methods including (but not limited to) restriction enzyme cloning, blunt-end ligation, and overlap assembly [see, e.g., Gibson, D.G., et al., Enzymatic assembly of DNA molecules up to several hundred kilobases. Nature methods, 6(5), 343-345 (2009), and GeneArt Kit (http://tools.invitrogen.com/content/sfs/manuals/geneartseamless-cloningandassembly_m an.pdf)]. Overlap assembly provides a method to ensure all of the elements get assembled in the correct position and do not introduce any undesired sequences.

[0080] The vectors generated above can be inserted into target cells using standard molecular biology techniques, e.g., molecular cloning. In an embodiment, the target cells are already engineered or selected such that they already contain the genes required to make the desired product, although this may also be done during or after further vector insertion.

[0081] Depending on the organism and library element type (plasmid or genomic insertion), several known methods of inserting the vector comprising DNA to incorporate into the cells may be used. These may include, for example, transformation of microorganisms able to take up and replicate DNA from the local environment, transformation by electroporation or chemical means, transduction with a virus or phage, mating of two or more cells, or conjugation from a different cell.

[0082] Several methods are known in the art to introduce recombinant DNA in bacterial cells that include but are not limited to transformation, transduction, and electroporation, see Sambrook, et al., Molecular Cloning: A Laboratory Manual (1989), Second Edition, Cold Spring Harbor Press, Plainview, N.Y. Non-limiting examples of commercial kits and bacterial host cells for transformation include NovaBlue Singles TM (EMD Chemicals Inc., NJ, USA), Max Efficiency® DH5a TM,One Shot BL21 (DE3) E. coli cells, One Shot @ BL21 (DE3) pLys E. coli cells (Invitrogen Corp., Carlsbad, Calif., USA), XL-Blue competent cells (Stratagene, CA, USA). Non limiting examples of commercial kits and bacterial host cells for electroporation include Zappers TM electrocompetent cells (EMD Chemicals Inc., NJ, USA), XL1-Blue Electroporation-competent cells (Stratagene, CA, USA), ElectroMAX T MA. tumefaciens LBA4404 Cells (Invitrogen Corp., Carlsbad, Calif., USA).

[0083] Several methods are known in the art to introduce recombinant nucleic acid in eukaryotic cells. Exemplary methods include transfection, electroporation, liposome mediated delivery of nucleic acid, microinjection into to the host cell, see Sambrook, et al., Molecular Cloning: A Laboratory Manual (1989), Second Edition, Cold Spring Harbor Press, Plainview, N.Y. Non-limiting examples of commercial kits and reagents for transfection of recombinant nucleic acid to eukaryotic cell include LipofectamineTM 2000, OptifetTM Reagent, Calcium Phosphate Transfection Kit (Invitrogen Corp., Carlsbad, Calif., USA), GeneJammer@ Transfection Reagent, LipoTAXI@ Transfection Reagent (Stratagene, CA, USA). Alternatively, recombinant nucleic acid may be introduced into insect cells (e.g. sf9, sf21, High FiveTM) by using baculo viral vectors.

[0084] Transformed cells are isolated so that each clone can be tested separately. In an embodiment, this is done by spreading the culture on one or more plates of culture media containing a selective agent (or lack of one) that will ensure that only transformed cells survive and reproduce. This specific agent may be an antibiotic (if the library contains an antibiotic resistance marker), a missing metabolite (for auxotroph complementation), or other means of selection. The cells are grown into individual colonies, each of which contains a single clone.

[0085] Colonies are screened for desired production of a protein, metabolite, or other product, or for reduction in protease activity. In an embodiment, screening identifies recombinant cells having the highest (or high enough) product production titer or efficiency. This includes a decreased proportion of degradation products or an increased total amount of full-length desired polypeptides collected from a cell culture.

[0086] This assay can be performed by growing individual clones, one per well, in multi well culture plates. Once the cells have reached an appropriate biomass density, they are induced with methanol. After a period of time, typically 24-72 hours of induction, the cultures are harvested by spinning in a centrifuge to pellet the cells and removing the supernatant. The supernatant from each culture can then be tested for protease activity and/or protein degradation.

Silk Sequences

[0001] In some embodiments, the modified strains with reduced protease activity described herein recombinantly express a silk-like polypeptide sequence. In some embodiments, the silk-like polypeptide sequences are 1) block copolymer polypeptide compositions generated by mixing and matching repeat domains derived from silk polypeptide sequences and/or 2) recombinant expression of block copolymer polypeptides having sufficiently large size (approximately 40 kDa) to form useful fibers by secretion from an industrially scalable microorganism. Large (approximately 40 kDa to approximately 100 kDa) block copolymer polypeptides engineered from silk repeat domain fragments, including sequences from almost all published amino acid sequences of spider silk polypeptides, can be expressed in the modified microorganisms described herein. In some embodiments, silk polypeptide sequences are matched and designed to produce highly expressed and secreted polypeptides capable of fiber formation. In some embodiments, knock-out of protease genes or reduction of protease activity in the host modified strain reduces degradation of the silk like polypeptides.

[0002] Provided herein, in several embodiments, are compositions for expression and secretion of block copolymers engineered from a combinatorial mix of silk polypeptide domains across the silk polypeptide sequence space, wherein the block copolymers have minimal degradation. In some embodiments provided herein are methods of secreting block copolymers in scalable organisms (e.g., yeast, fungi, and gram positive bacteria) with minimal degradation. In some embodiments, the block copolymer polypeptide comprises 0 or more N-terminal domains (NTD), 1 or more repeat domains (REP), and 0 or more C terminal domains (CTD). In some aspects of the embodiment, the block copolymer polypeptide is >100 amino acids of a single polypeptide chain. In some embodiments, the block copolymer polypeptide comprises a domain that is at least 80%, 81%, 82%, 83%, 84%, %, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a sequence of a block copolymer polypeptide as disclosed in International

Publication No. WO/2015/042164, "Methods and Compositions for Synthesizing Improved Silk Fibers," incorporated by reference in its entirety.

[0003] Several types of native spider silks have been identified. The mechanical properties of each natively spun silk type are believed to be closely connected to the molecular composition of that silk. See, e.g., Garb, J.E., et al., Untangling spider silk evolution with spidroin terminal domains, BMC Evol. Biol., 10:243 (2010); Bittencourt, D., et al., Protein families, natural history and biotechnological aspects of spider silk, Genet. Mol. Res., 11:3 (2012); Rising, A., et al., Spider silk proteins: recent advances in recombinant production, structure-function relationships and biomedical applications, Cell. Mol. Life Sci., 68:2, pg. 169-184 (2011); and Humenik, M., et al., Spider silk: understanding the structure-function relationship of a natural fiber, Prog. Mol. Biol. Transl. Sci., 103, pg. 131-85 (2011). For example:

[0004] Aciniform (AcSp) silks tend to have high toughness, a result of moderately high strength coupled with moderately high extensibility. AcSp silks are characterized by large block ("ensemble repeat") sizes that often incorporate motifs of poly serine and GPX. Tubuliform (TuSp or Cylindrical) silks tend to have large diameters, with modest strength and high extensibility. TuSp silks are characterized by their poly serine and poly threonine content, and short tracts of poly alanine. Major Ampullate (MaSp) silks tend to have high strength and modest extensibility. MaSp silks can be one of two subtypes: MaSp Iand MaSp2. MaSp Isilks are generally less extensible than MaSp2 silks, and are characterized by poly alanine, GX, and GGX motifs. MaSp2 silks are characterized by poly alanine, GGX, and GPX motifs. Minor Ampullate (MiSp) silks tend to have modest strength and modest extensibility. MiSp silks are characterized by GGX, GA, and poly A motifs, and often contain spacer elements of approximately 100 amino acids. Flagelliform (Flag) silks tend to have very high extensibility and modest strength. Flag silks are usually characterized by GPG, GGX, and short spacer motifs.

[0005] The properties of each silk type can vary from species to species, and spiders leading distinct lifestyles (e.g. sedentary web spinners vs. vagabond hunters) or that are evolutionarily older may produce silks that differ in properties from the above descriptions (for descriptions of spider diversity and classification, see Hormiga, G., and Griswold, C.E., Systematics, phylogeny, and evolution of orb-weaving spiders, Annu. Rev. Entomol. 59, pg. 487-512 (2014); and Blackedge, T.A. et al., Reconstructing web evolution and spider diversification in the molecular era, Proc. Natl. Acad. Sci. U.S.A., 106:13, pg. 5229-5234 (2009)). However, synthetic block copolymer polypeptides having sequence similarity and/or amino acid composition similarity to the repeat domains of native silk proteins can be used to manufacture on commercial scales consistent silk-like fibers that recapitulate the properties of corresponding natural silk fibers.

[0006] In some embodiments, a list of putative silk sequences can be compiled by searching GenBank for relevant terms, e.g. "spidroin" "fibroin" "MaSp", and those sequences can be pooled with additional sequences obtained through independent sequencing efforts. Sequences are then translated into amino acids, filtered for duplicate entries, and manually split into domains (NTD, REP, CTD). In some embodiments, candidate amino acid sequences are reverse translated into a DNA sequence optimized for expression in Pichia (Komagataella)pastoris. The DNA sequences are each cloned into an expression vector and transformed into Pichia (Komagataella)pastoris. In some embodiments, various silk domains demonstrating successful expression and secretion are subsequently assembled in combinatorial fashion to build silk molecules capable of fiber formation.

[0007] Silk polypeptides are characteristically composed of a repeat domain (REP) flanked by non-repetitive regions (e.g., C-terminal and N-terminal domains). In an embodiment, both the C-terminal and N-terminal domains are between 75-350 amino acids in length. The repeat domain exhibits a hierarchical architecture, as depicted in Figure 1. The repeat domain comprises a series of blocks (also called repeat units). The blocks are repeated, sometimes perfectly and sometimes imperfectly (making up a quasi-repeat domain), throughout the silk repeat domain. The length and composition of blocks varies among different silk types and across different species. Table 1 lists examples of block sequences from selected species and silk types, with further examples presented in Rising, A. et al., Spider silk proteins: recent advances in recombinant production, structure-function relationships and biomedical applications, Cell Mol. Life Sci., 68:2, pg 169-184 (2011); and Gatesy, J. et al., Extreme diversity, conservation, and convergence of spider silk fibroin sequences, Science, 291:5513, pg. 2603-2605 (2001). In some cases, blocks may be arranged in a regular pattern, forming larger macro-repeats that appear multiple times (usually 2-8) in the repeat domain of the silk sequence. Repeated blocks inside a repeat domain or macro-repeat, and repeated macro repeats within the repeat domain, may be separated by spacing elements. In some embodiments, block sequences comprise a glycine rich region followed by a polyA region. In some embodiments, short (-1-10) amino acid motifs appear multiple times inside of blocks. For the purpose of this invention, blocks from different natural silk polypeptides can be selected without reference to circular permutation (i.e., identified blocks that are otherwise similar between silk polypeptides may not align due to circular permutation). Thus, for example, a "block" of SGAGG (SEQ ID NO: 494) is, for the purposes of the present invention, the same as GSGAG (SEQ ID NO: 495) and the same as GGSGA (SEQ ID NO: 496); they are all just circular permutations of each other. The particular permutation selected for a given silk sequence can be dictated by convenience (usually starting with a G) more than anything else. Silk sequences obtained from the NCBI database can be partitioned into blocks and non-repetitive regions. Table 1: Samples of Block Sequences

Species Silk Type Representative Block Amino Acid Sequence

Aliatypusgulosus Fibroin1 GAASSSSTIITTKSASASAAADASAAATASAASRSSANAAASAFAQS FSSILLESGYFCSIFGSSISSSYAAAIASAASRAAAESNGYTTHAYA CAKAVASAVERVTSGADAYAYAQAISDALSHALLYTGRLNTANANSL ASAFAYAFANAAAQASASSASAGAASASGAASASGAGSAS (SEQ ID NO: 497)

Plectreurys tristis Fibroin 1 GAGAGAGAGAGAGAGAGSGASTSVSTSSSSGSGAGAGAGSGAGSGAG AGSGAGAGAGAGGAGAGFGSGLGLGYGVGLSSAQAQAQAQAAAQAQA QAQAQAYAAAQAQAQAQAQAQAAAAAAAAAAA (SEQ ID NO: 498)

Plectreurys tristis Fibroin 4 GAAQKQPSGESSVATASAAATSVTSGGAPVGKPGVPAPIFYPQGPLQ QGPAPGPSNVQPGTSQQGPIGGVGGSNAFSSSFASALSLNRGFTEVI SSASATAVASAFQKGLAPYGTAFALSAASAAADAYNSIGSGANAFAY AQAFARVLYPLVQQYGLSSSAKASAFASAIASSFSSGTSGQGPSIGQ QQPPVTISAASASAGASAAAVGGGQVGQGPYGGQQQSTAASASAAAA TATS (SEQ ID NO: 499)

Araneus TuSp GNVGYQLGLKVANSLGLGNAQALASSLSQAVSAVGVGASSNAYANAV SNAVGQVLAGQGILNAANAGSLASSFASALSSSAASVASQSASQSQA gemmoides ASQSQAAASAFRQAASQSASQSDSRAGSQSSTKTTSTSTSGSQADSR SASSSASQASASAFAQQSSASLSSSSSFSSAFSSATSISAV (SEQ ID NO: 500)

Argiope aurantia TuSp GSLASSFASALSASAASVASSAAAQAASQSQAAASAFSRAASQSASQ SAARSGAQSISTTTTTSTAGSQAASQSASSAASQASASSFARASSAS LAASSSFSSAFSSANSLSALGNVGYQLGFNVANNLGIGNAAGLGNAL SQAVSSVGVGASSSTYANAVSNAVGQFLAGQGILNAANA (SEQ ID NO: 501)

Deinopisspinosa TuSp GASASAYASAISNAVGPYLYGLGLFNQANAASFASSFASAVSSAVAS ASASAASSAYAQSAAAQAQAASSAFSQAAAQSAAAASAGASAGAGAS AGAGAVAGAGAVAGAGAVAGASAAAASQAAASSSASAVASAFAQSAS YALASSSAFANAFASATSAGYLGSLAYQLGLTTAYNLGLSNAQAFAS TLSQAVTGVGL (SEQ ID NO: 502)

Nephila clavipes TuSp GATAASYGNALSTAAAQFFATAGLLNAGNASALASSFARAFSASAES QSFAQSQAFQQASAFQQAASRSASQSAAEAGSTSSSTTTTTSAARSQ AASQSASSSYSSAFAQAASSSLATSSALSRAFSSVSSASAASSLAYS IGLSAARSLGIADAAGLAGVLARAAGALGQ (SEQ ID NO: 503)

Argiope trifasciata Flag GGAPGGGPGGAGPGGAGFGPGGGAGFGPGGGAGFGPGGAAGGPGGPG GPGGPGGAGGYGPGGAGGYGPGGVGPGGAGGYGPGGAGGYGPGGSGP

GGAGPGGAGGEGPVTVDVDVTVGPEGVGGGPGGAGPGGAGFGPGGGA GFGPGGAPGAPGGPGGPGGPGGPGGPGGVGPGGAGGYGPGGAGGVGP AGTGGFGPGGAGGFGPGGAGGFGPGGAGGFGPAGAGGYGPGGVGPGG AGGFGPGGVGPGGSGPGGAGGEGPVTVDVDVSV (SEQ ID NO: 504)

Nephilaclavipes Flag GVSYGPGGAGGPYGPGGPYGPGGEGPGGAGGPYGPGGVGPGGSGPGG YGPGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSG PGGYGPGGYGPGGSGPGGSGPGGSGPGGYGPGGTGPGGSGPGGYGPG GSGPGGSGPGGYGPGGSGPGGFGPGGSGPGGYGPGGSGPGGAGPGGV GPGGFGPGGAGPGGAAPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGP GGAGGAGGAGGSGGAGGSGGTTIIEDLDITIDGADGPITISEELPIS GAGGSGPGGAGPGGVGPGGSGPGGVGPGGSGPGGVGPGGSGPGGVGP GGAGGPYGPGGSGPGGAGGAGGPGGAYGPGGSYGPGGSGGPGGAGGP YGPGGEGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGEGGPYGP (SEQ ID NO: 505)

Latrodectus AcSp GINVDSDIGSVTSLILSGSTLQMTIPAGGDDLSGGYPGGFPAGAQPS GGAPVDFGGPSAGGDVAAKLARSLASTLASSGVFRAAFNSRVSTPVA hesperus VQLTDALVQKIASNLGLDYATASKLRKASQAVSKVRMGSDTNAYALA ISSALAEVLSSSGKVADANINQIAPQLASGIVLGVSTTAPQFGVDLS SINVNLDISNVARNMQASIQGGPAPITAEGPDFGAGYPGGAPTDLSG LDMGAPSDGSRGGDATAKLLQALVPALLKSDVFRAIYKRGTRKQVVQ YVTNSALQQAASSLGLDASTISQLQTKATQALSSVSADSDSTAYAKA FGLAIAQVLGTSGQVNDANVNQIGAKLATGILRGSSAVAPRLGIDLS (SEQ ID NO: 506)

Argiope trifasciata AcSp GAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGG ASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTL GVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNID TLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSS ASYSQASASSTS (SEQ ID NO: 507)

Uloborus diversus AcSp GASAADIATAIAASVATSLQSNGVLTASNVSQLSNQLASYVSSGLSS TASSLGIQLGASLGAGFGASAGLSASTDISSSVEATSASTLSSSASS TSVVSSINAQLVPALAQTAVLNAAFSNINTQNAIRIAELLTQQVGRQ YGLSGSDVATASSQIRSALYSVQQGSASSAYVSAIVGPLITALSSRG VVNASNSSQIASSLATAILQFTANVAPQFGISIPTSAVQSDLSTISQ SLTAISSQTSSSVDSSTSAFGGISGPSGPSPYGPQPSGPTFGPGPSL SGLTGFTATFASSFKSTLASSTQFQLIAQSNLDVQTRSSLISKVLIN ALSSLGISASVASSIAASSSQSLLSVSA (SEQ ID NO: 508)

Euprosthenops MaSpl GGQGGQGQGRYGQGAGSSAAAAAAAAAAAAAA (SEQ ID NO: 509) australis

Tetragnatha MaSpl GGLGGGQGAGQGGQQGAGQGGYGSGLGGAGQGASAAAAAAAA (SEQ ID NO: 510) kauaiensis

Argiope aurantia MaSp2 GGYGPGAGQQGPGSQGPGSGGQQGPGGLGPYGPSAAAAAAAA (SEQ ID NO: 511)

Deinopisspinosa MaSp2 GPGGYGGPGQQGPGQGQYGPGTGQQGQGPSGQQGPAGAAAAAAAAA (SEQ ID NO: 512)

Nephila clavata MaSp2 GPGGYGLGQQGPGQQGPGQQGPAGYGPSGLSGPGGAAAAAAA (SEQ ID NO: 513)

[0008] Fiber-forming block copolymer polypeptides from the blocks and/or macro-repeat domains, according to certain embodiments of the invention, is described in International Publication No. WO/2015/042164, incorporated by reference. Natural silk sequences obtained from a protein database such as GenBank or through de novo sequencing are broken up by domain (N-terminal domain, repeat domain, and C-terminal domain). The N-terminal domain and C-terminal domain sequences selected for the purpose of synthesis and assembly into fibers include natural amino acid sequence information and other modifications described herein. The repeat domain is decomposed into repeat sequences containing representative blocks, usually 1-8 depending upon the type of silk, that capture critical amino acid information while reducing the size of the DNA encoding the amino acids into a readily synthesizable fragment. In some embodiments, a properly formed block copolymer polypeptide comprises at least one repeat domain comprising at least 1 repeat sequence, and is optionally flanked by an N-terminal domain and/or a C-terminal domain.

[0009] In some embodiments, a repeat domain comprises at least one repeat sequence. In some embodiments, the repeat sequence is 150-300 amino acid residues. In some embodiments, the repeat sequence comprises a plurality of blocks. In some embodiments, the repeat sequence comprises a plurality of macro-repeats. In some embodiments, a block or a macro-repeat is split across multiple repeat sequences.

[0010] In some embodiments, the repeat sequence starts with a Glycine, and cannot end with phenylalanine (F), tyrosine (Y), tryptophan (W), cysteine (C), histidine (H), asparagine (N), methionine (M), or aspartic acid (D) to satisfy DNA assembly requirements. In some embodiments, some of the repeat sequences can be altered as compared to native sequences. In some embodiments, the repeat sequencess can be altered such as by addition of a serine to the C terminus of the polypeptide (to avoid terminating in F, Y, W, C, H, N, M, or D). In some embodiments, the repeat sequence can be modified by filling in an incomplete block with homologous sequence from another block. In some embodiments, the repeat sequence can be modified by rearranging the order of blocks or macrorepeats.

[0011] In some embodiments, non-repetitive N- and C-terminal domains can be selected for synthesis. In some embodiments, N-terminal domains can be by removal of the leading signal sequence, e.g., as identified by SignalP (Peterson, T.N., et. Al., SignalP 4.0: discriminating signal peptides from transmembrane regions, Nat. Methods, 8:10, pg. 785-786 (2011).

[0012] In some embodiments, the N-terminal domain, repeat sequence, or C-terminal domain sequences can be derived from Agelenopsis aperta, Aliatypus gulosus, Aphonopelma seemanni, Aptostichus sp. AS217, Aptostichus sp. AS220, Araneus diadematus, Araneus gemmoides, Araneus ventricosus, Argiope amoena, Argiope argentata,Argiope bruennichi, Argiope trifasciata,Atypoides riversi, Aviculariajuruensis,Bothriocyrtum californicum, Deinopis Spinosa, Diguetiacanities, Dolomedes tenebrosus, Euagrus chisoseus, Euprosthenopsaustralis, Gasteracanthamammosa, Hypochilus thorelli, Kukulcania hibernalis, Latrodectus hesperus, Megahexurafulva, Metepeiragrandiosa, Nephila antipodiana, Nephila clavata, Nephila clavipes, Nephila madagascariensis,Nephila pilipes, Nephilengys cruentata, Parawixiabistriata,Peucetia viridans, Plectreurys tristis, Poecilotheriaregalis, Tetragnathakauaiensis, or Uloborus diversus.

[0087] In some embodiments, the silk polypeptide nucleotide coding sequence can be operatively linked to an alpha mating factor nucleotide coding sequence. In some embodiments, the silk polypeptide nucleotide coding sequence can be operatively linked to another endogenous or heterologous secretion signal coding sequence. In some embodiments, the silk polypeptide nucleotide coding sequence can be operatively linked to a 3X FLAG nucleotide coding sequence. In some embodiments, the silk polypeptide nucleotide coding sequence is operatively linked to other affinity tags such as 6-8 His residues (SEQ ID NO: 520).

Silk-Like Polypeptides

[0088] In some embodiments, the P. pastorisstrains disclosed herein have been modified to express a silk-like polypeptide. Methods of manufacturing preferred embodiments of silk like polypeptides are provided in WO 2015/042164, especially at Paragraphs 114-134, incorporated herein by reference. Disclosed therein are synthetic proteinaceous copolymers based on recombinant spider silk protein fragment sequences derived from MaSp2, such as from the species Argiope bruennichi. Silk-like polypeptides are described that include two to twenty repeat units, in which a molecular weight of each repeat unit is greater than about kDa. Within each repeat unit of the copolymer are more than about 60 amino acid residues that are organized into a number of "quasi-repeat units." In some embodiments, the repeat unit of a polypeptide described in this disclosure has at least 95% sequence identity to a MaSp2 dragline silk protein sequence.

[0089] In some embodiments, each "repeat unit" of a silk-like polypeptide comprises from two to twenty "quasi-repeat" units (i.e., n3 is from 2 to 20). Quasi-repeats do not have to be exact repeats. Each repeat can be made up of concatenated quasi-repeats. Equation 1 shows the composition of a repeat unit according the present disclosure and that incorporated by reference from WO 2015/042164. Each silk-like polypeptide can have one or more repeat units as defined by Equation 1. {GGY-[GPG-Xi]ni-GPS-(A)n 2 }n3 (SEQ ID NO: 514). (Equation 1)

[0090] The variable compositional element Xi (termed a "motif') is according to any one of the following amino acid sequences shown in Equation 2 and Xi varies randomly within each quasi-repeat unit. Xi = SGGQQ (SEQ ID NO: 515) or GAGQQ (SEQ ID NO: 516) or GQGPY (SEQ ID NO: 517) or AGQQ (SEQ ID NO: 518) or SQ (Equation 2)

[0091] Referring again to Equation 1, the compositional element of a quasi-repeat unit represented by "GGY-[GPG-Xi]ni-GPS" (SEQ ID NO: 521) in Equation 1 is referred to a "first region." A quasi-repeat unit is formed, in part by repeating from 4 to 8 times the first region within the quasi-repeat unit. That is, the value of ni indicates the number of first region units that are repeated within a single quasi-repeat unit, the value of ni being any one of 4, 5, 6, 7 or 8. The compositional element represented by "(A)n 2 " (SEQ ID NO: 522) (i.e., a polyA sequence) is referred to as a "second region" and is formed by repeating within each quasi-repeat unit the amino acid sequence "A" n2 times (SEQ ID NO: 522). That is, the value of n2 indicates the number of second region units that are repeated within a single quasi-repeat unit, the value of n2 being any one of 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, the repeat unit of a polypeptide of this disclosure has at least 95% sequence identity to a sequence containing quasi-repeats described by Equations 1 and 2. In some embodiments, the repeat unit of a polypeptide of this disclosure has at least %, or at least 90%, or at least 95%, or at least 99% sequence identity to a sequence containing quasi-repeats described by Equations 1 and 2.

[0092] In additional embodiments, 3 "long" quasi repeats are followed by 3 "short" quasi repeat units. Short quasi- repeat units are those in which ni=4 or 5. Long quasi-repeat units are defined as those in which ni=6, 7 or 8. In some embodiments, all of the short quasi repeats have the same Xi motifs in the same positions within each quasi-repeat unit of a repeat unit. In some embodiments, no more than 3 quasi-repeat units out of 6 share the same Xi motifs.

[0093] In additional embodiments, a repeat unit is composed of quasi-repeat units that do not use the same Xi more than two occurrences in a row within a repeat unit. In additional embodiments, a repeat unit is composed of quasi-repeat units where at least 1, 2, 3, 4, 5, 6, 7,

8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 of the quasi-repeats do not use the same Xi more than 2 times in a single quasi-repeat unit of the repeat unit.

[0094] Thus, in some embodiments, provided herein are strains of yeast that recombinantly express silk-like polypeptides with a reduced degradation to increase the amount of full length polypeptides present in the isolated product from a cell culture. In some embodiments, the strain expressing a silk-like polypeptide is a P. pastorisstrain comprises a PAS-chr4_0584 knock-out and a PAS-chr3_1157 knock-out.

Equivalents and Scope

[0095] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments in accordance with the invention described herein. The scope of the present invention is not intended to be limited to the above Description, but rather is as set forth in the appended claims.

[0096] In the claims, articles such as "a," "an," and "the" may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include "or" between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

[0097] It is also noted that the term "comprising" is intended to be open and permits but does not require the inclusion of additional elements or steps. When the term "comprising" is used herein, the term "consisting of' is thus also encompassed and disclosed.

[0098] Where ranges are given, endpoints are included. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or subrange within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[0099] All cited sources, for example, references, publications, databases, database entries, and art cited herein, are incorporated into this application by reference, even if not expressly stated in the citation. In case of conflicting statements of a cited source and the instant application, the statement in the instant application shall control.

[00100] Section and table headings are not intended to be limiting.

EXAMPLES

[00101] Below are examples of specific embodiments for carrying out the present invention. The examples are offered for illustrative purposes only, and are not intended to limit the scope of the present invention in any way. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperatures, etc.), but some experimental error and deviation should, of course, be allowed for.

[00102] The practice of the present invention will employ, unless otherwise indicated, conventional methods of protein chemistry, biochemistry, recombinant DNA techniques and pharmacology, within the skill of the art. Such techniques are explained fully in the literature. See, e.g., T.E. Creighton, Proteins: Structures and Molecular Properties (W.H. Freeman and Company, 1993); A.L. Lehninger, Biochemistry (Worth Publishers, Inc., current addition); Sambrook, et al., Molecular Cloning: A Laboratory Manual (2nd Edition, 1989); Methods In Enzymology (S. Colowick and N. Kaplan eds., Academic Press, Inc.); Remington's Pharmaceutical Sciences, 18th Edition (Easton, Pennsylvania: Mack Publishing Company, 1990); Carey and Sundberg Advanced Organic Chemistry 3rd Ed. (Plenum Press) Vols A and B(1992).

Example 1: Production of recombinant yeast expressing 18B

[00103] First, we transformed a strain of P. pastoristo abrogate KU70 function to facilitate further editing and engineering. A HIS+ derivative of Pichiapastoris(Komagataellaphaffi) strain GS115 (NRRL Y15851) was electroporated with a DNA cassette consisting of homology arms flanking a zeocin resistance marker and targeting the KU70 locus. A map of the cassette is shown in Figure 1, and sequences are provided in Table 10. Transformants were plated on YPD agar plates supplemented with zeocin. This resulted in abrogation of KU70 function.

[00104] Then, we modified this strain to express a recombinant gene encoding a silk-like polypeptide. A HIS+ derivative of Pichiapastoris (Komagataellaphaffli) strain GS115 (NRRL Y15851) was transformed with a recombinant vector (SEQ ID NO: 462) to cause expression and secretion of a silk-like polypeptide ("18B") (SEQ ID NO: 463). Transformation was accomplished by electroporation as described in PMID 15679083, incorporated by reference herein.

[00105] Each vector includes an 18B expression cassette with the polynucleotide sequence encoding the silk-like protein in the recombinant vectors flanked by a promoter (pGCW14) and a terminator (tAOX1 pA signal). The recombinant vectors further comprised dominant resistance markers for selection of bacterial and yeast transformants, and a bacterial origin of replication. The first recombinant vector included targeting regions that directed integration of the 18B polynucleotide sequences immediately 3' of the A OX2 loci in the Pichiapastoris genome. The resistance marker in the first vector conferred resistance to G418 (aka geneticin).The second recombinant vector included targeting regions that directed integration of the 18B polynucleotide sequences immediately 3' of the TEF1 loci in the Pichiapastoris genome. The resistance marker in the second vector conferred resistance to Hygromycin B.

Example 2: Generating a library of single protease KO mutants

[00106] After successful transformation and secretion of 18B in a recombinant Pichia pastoris strain, 65 open reading frames (ORFs) encoding proteases were individually targeted for deletion (Table 2). Cells were transformed with vector comprising a DNA cassette with -1150 bp homology arms flanking a nourseothricin resistance marker. A plasmid map comprising the nourseothricin resistance marker is shown in Figure 2, and sequences provided in Table 11.

[00107] Homology arms used for each target were amplified by the primers provided in Table 7, and inserted into the nourseothricin resistance plasmid. Homology arms were inserted into the nourseothricin plasmid to generate cassettes comprising a nourseothricin resistance marker flanded by 3' and 5' homology arms to the target protease as shown in Figure 3A and Figure 3B. In Figure 3A, the resistance cassette (Nour Resistance Cassette) is shown flanked by homology arms (HA1 and HA2). In Figure 3B, details of the nourseothricin marker are shown, including the promoter from ILV5 gene from Saccharomyces cerevisiae (pILV5), the Nourseothricin acetyltransferase gene from Streptomyces noursei (nat), and the polyA signal from CYC1 gene from Saccharomyces cerevisiae.

[00108] The homology arms in each vector targeted one of the 65 desired protease loci as provided in Table 2. Transformants were plated on YPD agar plates supplemented with nourseothricin, and incubated for 48 hours at 30°C. Table 2 - Proteases targeted for deletion in P. Pastorisstrain Protease Gene Protease Protease Protease Gene Protease Protease Symbol ORF polypeptide Symbol ORF polypeptide Sequence sequence Sequence sequence (SEQID (SEQID (SEQID (SEQID NO:) NO:) NO:) NO:) PASchr4_0584 1 66 PASchr2-1_0172 34 99 (YPS1-1) PASchr3_1157 2 67 PASchrl-4_0251 35 100 (YPS1-2)

PASchr3_0299 3 68 PASchr4_0874 36 101 (YPS1-3) PAS-chr3_0303 4 69 PAS-chr3_0513 37 102 PAS-chr3_0866 5 70 PASchrl-1_0127 38 103 PASchr3_0394 6 71 PASchr4_0686 39 104 PASchrl-1_0379 7 72 PASchr2-2_0056 40 105 (MCK7) PAS chrl-1 0174 8 73 PASchr2-2_0159 41 106 PAS chrl-1 0226 9 74 PAS-chr3_0388 42 107 PAS-chr3_1087 10 75 PASchr3_0419 43 108 PAS-chr3_0076 11 76 PAS chr-3_0258 44 109 PAS-chr3_0691 12 77 PAS chr4_0913 45 110 PAS-chr3_0815 13 78 PAS-chrl-1_0066 46 111 PAS-chr-4_0164 14 79 PAS-chr2-2_0310 47 112 PAS-chr3_0979 15 80 PASchrl-3_0261 48 113 PAS-chr3_0803 16 81 PAS-chr2-1_0546 49 114 PAS-chr2-1_0366 17 82 PAS-chr2-2_0398 50 115 PAS-chr3_0842 18 83 PASchr4_0835 51 116 PAS-chr-3_0195 19 84 PAS-chr-1_0491 52 117 PAS-chr-4_0052 20 85 PASchr2-1_0447 53 118 PAS-chr2-2_0057 21 86 PAS-chr-3_0053 54 119 PAS-chr-3_0150 22 87 PASchr3_0200 55 120 PAS-chr-3_0221 23 88 PASchrl-3_0105 56 121 PASFragD_0022 24 89 PASchr3_0635 57 122 PAS-chr2-1_0159 25 90 PASchr4_0503 58 123 PASchr2-1_0326 26 91 PASchr2-1_0569 59 124 PAS-chrl-4_0611 27 92 PASchr3_1223 60 125 PAS-chrl-1_0274 28 93 PASchr2-1_0597 61 126 PAS-chr4_0834 29 94 PASchrl-1_0327 62 127 PAS-chr3_0896 30 95 PAS chr2-2_0380 63 128 PAS-chr3_0561 31 96 PAS-chr3_0928 64 129 PAS-chr3_0633 32 97 PAS chr-3_0184 65 130 PAS-chr4_0013 33 98

Example 3: Testing single protease knockout clones for reduced protein degradation.

[00109] Resulting clones were inoculated into 400 L of Buffered Glycerol-complex Medium (BMGY) in 96-well blocks, and incubated for 48 hours at 30°C with agitation at 1,000 rpm. Following the 48-hour incubation, 4 pL of each culture was used to inoculate 400 pL of BMGY in 96-well blocks, which were then incubated for 48 hours at 30°C. Guanidine thiocyanate was added to a final concentration of 2.5M to the cell cultures to extract the recombinant protein. After a 5 minute incubation, solutions were centrifuged and the supernatant was sampled and analyzed by western blot.

[00110] Western blot data for a representative clone of each protease knock-out is shown in Figure 3. Single protease deletions showed no discernable impact on the distribution of silk fragments detected via western blot.

Example 4: Generating a library of protease double knock-outs

[00111] In addition to the individual KOs, different pair-wise combinations of proteases were knocked out. These proteases were selected, in part, because they were paralogs that may have compensatory function with respect to each other.

[00112] To generate double knockouts, nourseothricin resistance was eliminated from the single protease knock-out strains produced in Example 2, and a second protease deleted by transformation with a second nourseothricin resistance cassette as provided in Example 2. Transformants were plated on YPD agar plates supplemented with nourseothricin, and incubated for 48 hours at 30°C. Double protease knock-outs tested are provided in Table 3. Table 3 - Protease double KO strains of P. Pastoris expressing silk-like polypeptide Double KO Strain Protease KO 1 ORF SEQ ID NO: Protease KO 2 ORF SEQ ID NO: 1 PASchrl-1_0379 7 PASchr3_0299 3 2 PASchr3_0394 6 PASchr3_0303 4 3 PASchr4_0584 1 PASchr3_1157 2 4 PASchr3_0076 11 PASchrl-4_0164 14 5 PASchr4_0584 1 PASchr3_0299 3 6 PASchrl-3_0195 19 PASchrl-4_0289 66 7 PASchr3_0896 30 PASchr2-2_0310 47 8 PASchr3_0394 6 PAS-chr3_1157 2

Example 5: Testing double protease knockout clones for reduced protein degradation

[00113] Resulting clones were inoculated into 400 L of Buffered Glycerol-complex Medium (BMGY) in 96-well blocks, and incubated for 48 hours at 30°C with agitation at 1,000 rpm. Following the 48-hour incubation, 4 pL of each culture was used to inoculate 400 pL of BMGY in 96-well blocks, which were then incubated for 48 hours at 30°C. Guanidine thiocyanate was added to a final concentration of 2.5M to the cell cultures to extract the recombinant protein. After a 5 min incubation, solutions were centrifuged and the supernatant was sampled and analyzed by western blot.

[00114] Figure 4 shows representative results from different protease double knockout strains. As shown, despite the presence of protein degradation in all single knockout strains tested, the combination of PASchr4_0584 + PASchr3_1157 protease knockout (Strain 3 from Table 3) resulted in the near-complete elimination of degradation products. None of the other combinations of proteases resulted in the elimination of degradation products.

Example 6: Additional protease knock-out strains

[00115] As shown in Examples 4 and 5, a modified Pichiapastoriscell capable of producing a desired protein (e.g., 18B) was transformed to delete proteases at PASchr4_0584 and PASchr3_1157 to mitigate degradation of the desired protein. We further knocked out one or more additional proteases to enhance the production of full-length products and minimize degradation.

[00116] For each additional knockout, an additional protease gene was deleted from a single protease KO (IX KO), double protease KO (2X KO), triple protease KO (3X KO), or quadruple protease KO (4X KO) by transformation with a nourseothricin resistance cassette with homology arms targeting the desired gene as provided in Example 2. The protease genes knocked out in each strain are shown in Table 4: Table 4: 2X-5X KO Strains KO Strain Protease Genes Knocked Out 2X KO PASchr4_0584 (YPS1-1) PASchr3_1157 (YPS1-2) 3X KO PASchr4_0584 (YPS1-1) PASchr3_1157 (YPS1-2) PASchr3_0688 (YPS1-5) 4X KO PASchr4_0584 (YPS1-1) PASchr3_1157 (YPS1-2) PASchr3_0688 (YPS1-5) PASchrl-1_0379 (MCK7) X KO PASchr4_0584 (YPS1-1) PASchr3_1157 (YPS1-2) PASchr3_0688 (YPS1-5) PASchrl-1_0379 (MCK7) PASchr3_0299 (YPS1-3)

[00117] The resulting cells were isolated on selective media plates (by auxotrophy or antibiotic resistance marker) and individual clones were isolated for further testing. Individual clones were tested by liquid culture assay under product protein producing conditions as follows: Isolated colonies of each strain were inoculated into 400 L of Buffered Glycerol-complex Medium (BMGY) in 96-well blocks, and incubated for 48 hours at 30°C with agitation at 1,000 rpm. Following the 48-hour incubation, 4 pL of each culture was used to inoculate either 400 pL of BMGY or 400 pL of YPD (Yeast Extract Peptone Dextrose Medium) in 96-well blocks, which were then incubated for 48 hours at 30°C with agitation at 1,000 rpm.

[00118] Protein expressed by the cells was isolated and analyzed for degradation as follows: Guanidine thiocyanate was added to a final concentration of 2.5M to the cell cultures to extract the recombinant protein. After a 5 min incubation, solutions were centrifuged and the supernatant was sampled and analyzed by western blot.

[00119] Figure 5 shows the results of a Western Blot of purified protein from the 2X KO, 3X KO, 4X KO and 5X KO strains inoculated in BMGY or YPD. As shown, the deletion of additional protease genes from the strain having the PASchr4_0584 + PASchr3_1157 protease knockout (Strain 3 from Table 3) resulted in the further elimination of degradation products.

OTHER EMBODIMENTS

[00120] It is to be understood that the words which have been used are words of description rather than limitation, and that changes may be made within the purview of the appended claims without departing from the true scope and spirit of the invention in its broader aspects.

[00121] While the present invention has been described at some length and with some particularity with respect to the several described embodiments, it is not intended that it should be limited to any such particulars or embodiments or any particular embodiment, but it is to be construed with references to the appended claims so as to provide the broadest possible interpretation of such claims in view of the prior art and, therefore, to effectively encompass the intended scope of the invention.

[00122] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, section headings, the materials, methods, and examples are illustrative only and not intended to be limiting.

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, 'o , 'o M U 'o M 'o 4-) 1 M 4-) 'o U 4-) M M U 4-) U M M M 10 U U M 4-1 4-) M U M 8 M M E t E M 'j Co Co , 'o t M M 'o 'o 'o , M M

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J-j J-j m J-j co m J-j co co J-j u co co u co u u co co u J-j m m J-j J-j m J-j co u J-j J-j u m J-j u co m J-j J-j m J-j u u J-j u m m m m m u m m J-j m J-j m u J-j J-j u co m co co co u m m J-j m co J-j co J-j J-j 4-1 u 4-1 co J-j m J-j u u u J-j m J-j m co J-j m J-j co m u J-j u u J-j u co J-j J-j u co J-j J-j m m m u m m m m m m u m m m J-j m m m m m m J-j m m u m J-j J-j u J-j J-j m m J-j J-j co m m J-j u J-j co J-j J-j J-j m J-j u m m u co co J-j m u u m J-j J-j J-j J-j co u co u co J-j co u J-j u J-j m co co u J-j co co J-j J-j co u m J-j J-j u u J-j J-j co 4-1 4-1 co J-j u co co u J-j co J-j J-j J-j u co co M J-j J-j M u m J-j m u m m m m J-j J-j u m u u m u m u m m m J-j J-j J-j m u u m J-j J-j m J-j u J-j u J-j J-j m u u J-j J-j co m m u J-j co co u co co J-j u J-j co J-j J-j u J-j co co m J-j u m m J-j m J-j m J-j u m m u u u m u u u m m u J-j u u m m m m m m m m m u J-j m u u J-j m m J-j m m m m u u m m m u m m m u m m m m m u m u co m u co m J-j J-j m u co co u co co u u co co m J-j J-j co m J-j u co co m co u m u m m m m J-j J-j u m m m u J-j J-j J-j m u J-j m u u u J-j m m m m m u co co J-j u m u J-j m J-j J-j m J-j J-j J-j J-j u m m u J-j J-j co co m co u m co J-j m J-j co m J-j u m J-j u m m u m J-j J-j 4-1 u 4-1 m u u J-j u m m m u m u u m u m m m m u m J-j u J-j J-j m m J-j J-j m m u u J-j J-j J-j m u co J-j co m J-j J-j m J-j co co co co m J-j co J-j J-j J-j co m m J-j J-j co u J-j m co co J-j m u m m co co J-j J-j u m m m m co J-j m m co J-j co J-j m J-j u J-j u u co J-j co J-j u co co J-j co J-j co J-j m u co J-j co m J-j u J-j J-j u J-j J-j u u J-j co m co u J-j J-j u u J-j co u co u J-j m J-j J-j co u m co J-j u u u J-j J-j J-j J-j m J-j J-j J-j J-j m J-j J-j M u u m M m m m J-j m u u m u m m u m J-j m co co u co m m u m co u co m J-j co co co m co co co co J-j J-j co J-j J-j J-j J-j M J-j J-j M u m co J-j u u co J-j co J-j m m J-j u m u J-j m m m u J-j 4-1 4-1 m J-j m m m u m u u u m m J-j u m m m u J-j m u J-j m co J-j co u J-j u J-j J-j m co co m m u m m m m J-j m m m u m J-j u u m m m co co co co J-j m u J-j m co u m u u co u m co m J-j J-j m J-j J-j u u co co u m u m m u u m u J-j m m u m m J-j J-j m u m m u m m m m J-j m m u J-j u m J-j co u J-j co m J-j u J-j J-j J-j m u u m J-j u m J-j J-j m J-j co co J-j J-j m J-j 4-1 4-1 4-1 4-1 m u J-j m J-j J-j m m J-j J-j m u J-j u co J-j J-j J-j co m co m J-j J-j J-j co co m -1-i m m co m co u m m J-j co co J-j u co J-j J-j m m m m m J-j u u J-j u m u J-j J-j m J-j J-j co J-j co m J-j m m co u u u J-j u J-j u m m m m J-j J-j u J-j m J-j m J-j u m u u u m m J-j co co co co co J-j co J-j J-j co co co m co m m J-j u J-j u u co co co co J-j u co J-j u m u co u m J-j m u co co J-j J-j u J-j m J-j m co m J-j co co m co u u u u m m m J-j m m m m m u m m u co co m J-j m J-j co u u J-j co m J-j u co m co u m co m J-j J-j J-j m m co u J-j m J-j J-j co co J-j J-j m m co J-j m u m co m u u J-j co m J-j m u m m m m J-j u m m m m u u u u J-j J-j u u J-j J-j J-j J-j J-j m J-j u co J-j co u u m co co co co m J-j J-j u m u m m J-j J-j u J-j J-j m co m m J-j co co u co co J-j co m J-j m J-j m co m co J-j J-j co m J-j co J-j u J-j co J-j u J-j co J-j m m co m J-j co co co m J-j m co co m co co m u co J-j u J-j J-j m co m u co co u co m co u m J-j u J-j co u co m J-j u u u m m u m m J-j m m m m m J-j m u co J-j u m J-j u J-j J-j co co J-j u J-j m u u J-j co J-j m m u u m co u m co co m co u u m u co m u co co m J-j m u u m J-j J-j co u m co J-j u u m u J-j u u J-j u m J-j m m co u co co m co m J-j J-j J-j u u J-j co co m J-j J-j m u J-j m u m m J-j m m m m m u J-j m co J-j m J-j co J-j m u J-j u co J-j u u u m u u co u co J-j J-j m u J-j m J-j m co J-j J-j J-j co J-j J-j J-j co co m J-j m m u m m co u J-j u J-j J-j co J-j u u J-j J-j co u J-j M u u J-j M J-j u m m m m m m J-j m m m m m m m u J-j m u u u m m J-j J-j u m J-j m u u m m m co u u m J-j J-j co u co co co u m J-j co m u u m J-j J-j m co u u m J-j co co J-j J-j m co m J-j m m J-j m J-j co J-j co J-j J-j u co u co u u co J-j m J-j co u m u m u u co J-j u m u J-j u co J-j J-j m u m m m J-j co J-j J-j J-j m u J-j co J-j J-j co m J-j co J-j m J-j co u co m J-j u J-j J-j co m m J-j co m u J-j co m m co J-j m co co u J-j m m m m u u u m J-j J-j J-j J-j J-j J-j J-j m co m m co u J-j u J-j u co m J-j J-j m co co J-j J-j m J-j u m u J-j J-j co co co J-j m 4-1 4-1 4-1 u 4-1 4-1 4-1 4-1 co J-j J-j co co J-j m co co u m J-j u u m J-j J-j u u J-j m u u co u m J-j u m J-j m m m u J-j J-j m u m m u m J-j m J-j m J-j J-j m J-j m J-j co J-j J-j J-j J-j u m m u m u J-j u J-j J-j J-j u J-j m m m m m m J-j m m J-j m u co co J-j u u J-j m m J-j u co J-j co J-j u u m u J-j co co J-j m co J-j J-j co co co co co u u J-j co co J-j J-j m m m J-j J-j m J-j u u J-j u m co u u m J-j co u co u u co J-j u u J-j J-j u J-j u co u J-j m J-j J-j J-j m co co J-j m u co u co u m co m J-j u u J-j co J-j u u J-j J-j m m co co co J-j co co co J-j J-j J-j m J-j J-j u 4-1 m 4-1 J-j m J-j J-j m m m u co u co m u J-j u co co m J-j co co m J-j u u J-j co J-j J-j J-j m co J-j m J-j u J-j J-j co co J-j u co co u co co J-j u m m co J-j co u co J-j m co m u m J-j J-j u m J-j m co m J-j co co J-j u J-j J-j u J-j m J-j m u u m u m J-j m m J-j m m m J-j J-j J-j m m m u m m m m m u m u u J-j J-j m co J-j co J-j J-j 4-1 m 4-1 co J-j J-j u m co co J-j m m m co m m m J-j J-j m co J-j co co u co J-j m u m m u J-j J-j J-j u m m m m m m m J-j co m m co co co co u u J-j u m m m J-j m u m u J-j u m m J-j J-j u u u m m m m u J-j J-j m u u co J-j m m co J-j m u m m J-j J-j co J-j J-j u co m co J-j m u co m J-j co u u m J-j u co co m m co m J-j co J-j m co J-j J-j co J-j u co co co m u m m J-j u m m u u co u co J-j u J-j m J-j u m J-j co u J-j m m co J-j co J-j co J-j J-j m m J-j m u J-j m co m m u u m u J-j u co m J-j J-j J-j J-j m co co m J-j J-j co co co J-j J-j J-j m J-j J-j m u m m u J-j J-j m m m J-j u m m m J-j m m J-j J-j m u m u J-j u u m m m u m J-j m u u J-j m m m J-j m m m m u J-j co u u J-j J-j co J-j m J-j co m co u J-j m co co m m u u J-j m m m m m m m m m m J-j J-j m J-j u m u J-j co J-j J-j u J-j u J-j u J-j m J-j u u J-j J-j J-j u m m m m u u m m u m m co u J-j m J-j m co u u J-j 4-1 4-1 u u m co m u m m u u u J-j J-j m u u J-j m u J-j u J-j J-j m u J-j J-j co u m u co co J-j m m J-j J-j co J-j m m m J-j co J-j J-j J-j co co m J-j J-j J-j J-j u co J-j J-j u J-j J-j m J-j co m m u co co u J-j J-j co J-j m m co J-j co co co u J-j J-j u J-j m J-j m m m co u m m J-j J-j J-j J-j co J-j J-j m J-j co u J-j J-j J-j m J-j m J-j co J-j co m u J-j m J-j J-j u J-j u m m m m m J-j J-j u u m J-j u m u co u co m J-j J-j u u co J-j m co co co m J-j co m co m co co m J-j co J-j J-j m co u J-j co m u m J-j J-j m m u m J-j u m J-j m J-j u m m J-j co u J-j u co J-j J-j m m J-j co m u co co m m m J-j u u co J-j u J-j u co co u co J-j m co m u J-j J-j u co J-j J-j J-j co J-j u J-j m u m J-j m 4-1 4-1 m m m m u m m m m m m m J-j co co J-j J-j J-j u u J-j co m J-j J-j J-j J-j J-j m m m m u m m J-j m m J-j J-j J-j u J-j J-j J-j u m u u m m J-j co co J-j u m u m co m co u co co m m u J-j m J-j J-j J-j J-j m J-j J-j J-j co co m J-j co J-j J-j m u co co u m m co J-j m J-j J-j co m u J-j J-j u J-j 4-1 m 4-1 4-1 u 4-1 m m m m u u m m m J-j J-j J-j u u u co co u m m u m J-j m J-j J-j u m u J-j J-j co J-j co u u m u co u m J-j co m m u m m u

MICI 2019/070246 PCT/US2017/054997

4-1 U 4-1 11 M U 4-1 11 M 11 4-1 -1-1 M 10 -1-1 10 M 4-1 4-1 4J 11 U 11 M U M -1-1 M 'o M 'o t , , U 'o 'o , U M , 'o M t t 'o 'o , M 'o 'o M U 'o 'o 'o , 'o co co -1-1 MM 4J U 11 4J 11 4J 11 11 4J 10 -1-1 U 4J M M M M 4J 4J U 4-) 'o , U , M U , M , m u 'o M M t M t t M 4J M M 8 t 8 M M 4-) 4-) U 4J M U U U 4J U 10 10 M U M 10 U U u U M U 'o U U , 'o 4-) 4-) 'o , U M , , 'o 'o , , U , 11 U M 11 4J 4J t U 10 -1-01 U -1-1 4J U 4-) 4J 11 11 U 11 u M 4J 4J U 10 R I , M 'o (0 , M M

, M 4J t 'o 'o U U U (' U t 'o M 'o 'o U -1-1 U 10 U 10 U 4J M 4-) 'o , M M M M M U 4-) 4-) 4-) U M 10 U U 10 M M M , 'o M 'o 'o -) u (0 M 4J M 4-) 4-) 4J -1-1 U -1-1 -1-1 U M t j 'o U , t 4-1 t U 10 10 4-) 4-) 4-) (0 4-) 4-) u 1 4-) U (o 4-) 4-) (0 (0 4-) U 4-) (I , , 'o , M tt MM8 MMMM 4-) 4-) (0 4o) t M U 4_) M m u u M (I U CO U U 4-) 10 -1-1 -1-1 U (0 4-) 4-) (0 , 'o 'o M 4-) 10 10 -1-1 M U 4-) U U 4-) t US I u 10 U M U U 10 10 m u m 1 4-) U 4-) U U 4-) 4-) 4-) M U 4-) U M 4-) 4-) M 4-) 4-) U M -1-1 10 U 10 m m u t -1-i I (I M M M , U 'o M -1-1 -1-1 M 'o M U u m t M , t , M M 4-) M 4-) t (M 10 M P 10 4-) (0 U 'o ,J-) M 4-) 10 m 10 1 u 4.) U M M M U M 4-) 'o 'o M 'o , (0 4-) U t 4-) 4-) U ,M (I U m 4- M J_) J_) Co 'o Co U U 4.) 4.) M (o U M , U M (I M -1-1 -1-1 U (o M (I 'o M m I U U Co 4.) Co U U u I I m I M R m (0 (0 4-1 mumulmmummumsmummu 'o m 4-1 -1-110lomt co co M U 4-) 4-) 1 u 10 1 4-) 4-) 4-) U M M 4J M 4J 4-) U 4-1 U 4-) U U M ,4-1 mu (0 4-) U M U M U M co 10 t MM M u 1 10 'o m m M 10 'o M (1 -11-01 10u1101 10m 10 uu u 4-) 10 4-) M 4-) U M 4-) M U U M 10 10 -1-1 10 M 10 'o t m u mj U M (I U (1 4-) 4-) M t M 4-01 , 'o 'o , U 'o , 'o , U U 'o 'o , U M M 4-) 4-) u I u u 10 (1 (1 U 'o

, co u U 'o , M U (0 4-) M U M M (0 u I 4J M M 4-) 4-) M U M 4J u u U U M M (110 U U U M M M M 4-) U U 4-) 10 10 U 10 U U U , M t t M M , 'o U 'o t 'o 10 -1-1 M , M , 'o t 'o U , M 'o 'o 'o U , U 'o , , -1-1 10 4-) M M M M t M M U 'o u 10 1 4-) U 4-) 4-) 10 10 4-1 10 M MU 4-) U U M U M M M M 'o 'o 'o 'o u (0 U -1-1 10 U M M 'o U , M , , , 'o M 'o 'o (I M M (I U (I U 4-1 4-1 M 4-) U 4-) m m m I I m m M 4-) 4-) U (0 t 4-) M U 1 10 P u I u M , 'o M

, U 4-) M M U M U M U M M -1-1 M 4-) M U M M , U u m u 4.j 4.j U J-) U M U 4J (I (I 'o 'o 'o 'o , 'o 'o 'o U M M , M , U M (I U M u 4-) U M 4-) 4-J (o U 4-) (0 M m u J M -1-J M M U M M M M M 4J M 10 10 m R m 'o 'o 'o m co 4-) 4_) J_) J_) U U 10 t 10 U M M IJ U IJ 4-) MM MMUU t,tM , 4-) M J-) J-) (0 J-j u J-j co co m (0 u U 4-) (I u U 4-) M (0 4-) R R Co M U Co U 4-) U (o U 10 'o M 'o U CO CO M 4- (0 4-) U U M (I co 'o M , , 'o , 'o U t 1100 -1-1 M U M 10 t M M luo 4-) M M 4-) M m 1 10 u U M t 8 M t M t t t 4-) M , U -1-1 M U M 'o I I m m 4-) 4-) 4-) 4-) (0 4-) 'o 'o , 'o (I (I 10M U -1-1 -1-1 M M 4-) 4-) M 4-) 4-) M 10 10 M 10 4-) (0 M (o U U M U M M U 10 u 4-) 4-) U 4-) 'o 'o 'o'o M , 'o M M 'o , 'o , M 'o U 'o I u U M 4-) U U 4-) M M M 4-J (0 4-) 4-) M 4-) 10M U U M U U M M M M 4J U U M 'o 'o , U , (I M M 10 M -1-1 u u , 'o U U t 'o t , , 'o 'o M U M M 2 U 'o 4-) u M (0 4-) 4-) P 10 P 10 10 U M t U 10 10 t 4-) M 4-) 10 4-) U M M u M M 4_) U U 4-) 4-) 4-) t U -'Il U 1 10 M M M M U 'o 'o 2 'o 'o M M M 10 U M (0 M , , 'o -1-1 10 M -1-1 M M 4-) U M M M u 4-) M 4-) -1-1 10 10 10 P t (I (I M M (1 4-) 4-) 4-) U J-) t 10 10 U , , U 'o M 'o M , 4-) , , , 'o 'o (, j u j 1 10 10 1 10 'j(1 'o 'j(I J-j u J J U 4-) M 4-) M 4-) M M U M 10 10 U M U 4-) U 4-) M M 10 M M 4-) M U M M M 4-) CO M M 'o , 'o 10 t m P u 10 M . . . U , M 'o U 10 R 10 R u u U U U -1-1 U CO U M 4-) U u M 4J 4J 4J U M M 4-) M M 10 U 10 M U -1-1 M U U 'o 10 m CO (0 M 4-) U -1-1 10 -1-1 M 10 (1 M 'o 10 1 1 u R 1 10 10 m 4-) 4-) M M U M 4-) -1-1 U I u 1 10 10 m U U U 4-) M M 4-) M 10 M -1-1 10 10 4-) (0 , , U 'o M M 'o M U U M U U M 4-) u 10 t 1 4-) U 'o 'o M U , , M 'o U 4-) 4-) M -1-1 M 10 10 -1-1 10 4-) 4-) U M M M , 'o 'o U , M U M 4J U M u(0 'o M u M , , M U 'o M 4-) U M M 4-) U 4-) M U 4-) U M U t um 4 M t 4-) M M M U M M M (' 'j 'j 'o t U , 4-) CO -) E M M , U , M E t MM M t t 2 t M (1 4-) 4-) 4-) 4-) 4-) M t 10 -1-1 10 U t (11 M M R u 'o 1 10 1 10 10 (0 (0 U (0 4-) 4-) U (0 M 4-) 2 t 4m M MM t t t M M M 4-) M M M 4-) U 4-) U 4-) MU JUJ UU U M M M 8 M MM t t U 'o , M U t 'o M 'o (I m 10 t 110 M M 4-) U M -1-1 10 10 10 U M CO 4-) U t 4-) M M M 4-) u J-j J-j J-j UU u 10 'o U 'o U , , U 'o , , 'o M M 'o 4-) (0 t IMO US (110 M M M 4-) U U 4-) M 4-) 4-) U RM M (0 4-) 4-) JJ M CO M (' (' J-j u t 10 4-) U , , U 'o 'o , M 'o , , 'o (I U M (I U M U 'o 'o 'o 'o u J-j M , 'o 4-) -1-1 -1-1 M 10 10 M U 4-) M 4-) u 10 10 t I u IMO I M 10 U U 10 U 4-) 4-) 4J 4J U M 'o M 'o 'o M U , 'o , U M 'j M U 'j U U U 4J P 1 10 10 1 10 M U M M M 4-) M U (o (o U Co U 4J M M U -1-1 10 U 10 -1-1 U 4-) (I , M M , 'o M 'o 4-) M 4.) M M 8 M 2 t I I m , 'o , , , 'o 10 u 4-) M U M U M M M 10 10 M U M U 4-) 4-) M M 4-) M M M 10 M t 10 -Il 10 4-) co u , U , t 4-) M U 4-) U , t M U U 'o , 'o , 'o 'o U M , 'o , M (0 4-) 4-J 4-J M M 'o M 'o 4-J 4-J CO U 4-J M U 4-) 4-) U U 4-) 4-) U M U 4-) 10 M -1-1 -1-1 10 U 4-) M M M 4-) M M 4-) M 10 -1-1 -1-1 M 10 4-) U M 'o M , 'o 'o t tM tU M ,M 'o M M 4J 4J(I 4J M M 4J 4-) M M 'o U 4-) M U 'o 4-) ,M 'o 4-) 'o U U 4-) t M U 1 u 10 U M I 'o 'o u 10 , U 'o 'o -1-1 M t lu U g M 4-) CO 4-) M 4-) 4-) M U M 'o MU 4-) M 10 4-) M U U 10 (I M 1 10 U u 10 U (1 m U 4-) M 4-) 'o m u m 4-1 -1-1 10 4-1 u m m , M U 'o , 'o M 4J U U M 'o , U tj u , (, , u m u 4-) 4-) U M 4-) 4-) M 4-) 10 10 M U U M M M 4-) U U 4-) M U 4-) 4-) J U CO u u M , , 'o 'o , M , 'o 'o , M M t t 'o , M 'o U 'o 'o U m m m m 4.) M )

J 4-) U M U U M U 4J 4J U 1.) u m m M M 4-) U 4-) t M 4-) (0 m m m u t M MM M M t lu (Ul m 1.) m 1.) M , M M , 'o u u M M U (0 4-) (0 (0 4-) CO U U CO 4-) CO t t MM t M 4-) M M 4-) 4-) M 4-) M 10 u u u 10 R 1 10 M M U M U M .) U Co M M j 4-)(0 4-) 10 R I u t I M (I U U E 2 8 MM M M U M M U U M U M M 4-) 4-) 4-) 4-) M MM M 1 m 4-) 4-) M 4-) M I m (0 u 10 M M M -1-1 4-) M 'o m u M 'o 'o M 'o 'o , U 4-) 10 U 1 (0 (0 'o , M 10 -1-1 -1-1 -1-1 U M M 4-) 4-) , M (0 4-) (o 'o t M 4-) M U 10 -1-1 M 4-) 10 u 'o 'o 'o , 'o U 'o M 'o 'o M 'o 'o 'o 'o 'o M 'o (I M M M (I M M U M 4-) M 4-) U t t 10 10 M -1-01 10 u (0 4-) U M 4-) U 4-) (0 M 4-) 1 1 10 m 10 10 1 P 10 'o 'o M U U 'o u

't

MICI 2019/070246 PCT/US2017/054997

4J 4J t IUII t U M M 4J 10 M U 4J U 11 11 U 4J M 11 10 -1-1 10 10 U 4-) M M M M M 'o 'o U 'o 'o M U 'o 'o M t M U t M U t M 'o M M M U 11 4J 11 4J 4J 4J M 11 M 10 U -1-1 U -1-1 10 10 M M 4J 11 11 10 10 41 U 1 M M U IJ

U U JJ JJ U 4J u m m u m t t) t)) m Im m t u M 4J 4J 4J o 'o U U t U 'o , 'oMM M 'o 'o 'o m'o 'o M t M 4-OJ M U U U M 11 11 U U M 11 4-OJ 11 u m 10 U 10 -1-1 10 10 U 11 11 , M t M , 'o t , M , , M , 'o U U U U U t t , 'o M U 10 4-J U 4-J 10 U -1-1 U U U -1-1 10 4-J U U U 11 U 11 11 11 10 -1-1 U 10 U M M 'o 'o M , , 'o U t M M 'o M , 'o 'o U M 'o t 'o U 'o 'o 'o 'o , M , 10 4-) 4-) 4-) M M M 11 t 11 11 11 U U 11 10 10 10 10 IJ U 10 U 10 m M U u m m 1 4-) 4-) (0 M U 'o U U 4J 4-) U 4-) (0 4-) 4-) M 4-) 4-) M t M M U U , U M M U M M M M U M 4-) U (0 4_) (o I u t t I u t 4-) 4-) 4-) U 4-) (0 (o (o M M M 4-) U U t CO M m M , U 'o U U u (0 4-) t M U U U 10 4-) 10 -1-01 U U U M 'o 4-) U U 4-) Co M M U 'o 4-) M M 4-) M M U M 'o U U 'o U u M , , M , U U 4_ IJ IJ 4-) 10 1 10 10 U 'o 'o , M U 'o U U U 'o 'o 'o 'o 1 4-) U 4-) 4-) 4-) 'o 10 4-) M U U U U10 -10 'o 'o M 'o 'o o U t U M M U 'o ' ' m U (0 4-) M 4-) U U -1-1 U -1-1 4-) 10 10 10 4-) 1 4J 4J 4J M U (0 4-) (0 10 10 M U U U 4-) 4-) U 'o t m m m m u M , M M M 'o M 0 10 'U 'o U 4-) t M U U M M U M -'Il -'Il U M 4-) 4-) 110IMO t t MM (11 'o 'o , , U , U M , 'o 10 Im u 10 10 10 4-) 10 4_) 4-) U t M U 4-) 4-) U U M 4-) U M (0 4-) u 4J M M M M M g M 4J 10 10 1 1 u IJ U 4-) , 'o , 'o , u u I-) M U M U U U U M U M M

, U 4-) (o (0 4-) (0 U t 4-) 4-) t 4M t t t 4J U 4J t t 2 M 4-) 4-) U U 4-) m M 4J U U 4-) 4-) 4_ U M 4-) 4-) 4-) 10 U 10 t U U lu 10 1 u u 1 10 co 4-) U U U 4-) M 4-) M M U U M M u u U M M 4-) M M 4-) CO M CO -1-1 10 -1-1 4-) M . . . . U U m t 8 , , M t M M M M -1-1 4-) M U 4-) M U M 4J 4J U 4-J U (I (0 1 u 4-) U -,-, u u U U 4-) 'o 4J U MMM'o , M M 'o M M 'o , (' (' j j m 'o u (, M U 4-) M U U 10 M 10 10 -1-1 M U 4-) 4-) 4-) 'o U , U U 'o M 'o 'o U 'o 4J 4J U 4J U Co 4-) m t M M U (I M M M 10 10 U (0 M M 4-) U 4-) 4-) M M U U (0 M 4-) 4-) 4-) (o (0 4- ) M U 4_) U M 'j 4-) M M M 4-) M 10 10 U (1 (o Co U U (I 4_) M (I M U (I M U u 10 4-) U M M M M M M M U M U Co Co M 4-) U M U M 'o t M I 1 10 u I 1 10 M U 10 t U 4-) u IU I m 10 10 u m 'o 'o 'o , , , 'o U 4-) U U 4-) U 4-) t U 4-) U 4) M 4-) 4-) M M 1 10 u U -IJ 4-J 4-1 U 'o u , u 4M U 4-) M U , M , 'o 'o , , 4-) 4-) M 4-) CO M U 4J 4J , M 'o , 'o U U M , 'o 4-) M U 4-) 4-) M M U M U 4-) M U U U M M M 8 M 4-) U 10 M M -1-1 4-) 4-) 4-) 4-) 4-) M 'o , M U M 'o 'o 4JM M M , 'o , , U 4' M U M I I M 9 41 M M 4-) 4-) U U U M 'o 41 M M U M M R U M 4-) 4-) u U 'o 4-) 'o U M M U t ,M 'o M 4J U M 'o M 'o M 'o M U M M M M M M 'o tM M , U 'o M 'o 'j(I (I U M 4-) U M U M u u m u 0 U CO 4-) CO M 4-) 4-) 4-) (0 M 4-) (0 'o t U , U t U (1 (11 4-) 4-) (0 Co .) Co 10 1 u j u u ( 4-) 'j 'j 'j M M 4-) 4-) u I M M 4-) M U M 4J U M 4J 4-) 4-) U M 'o 'o M u (0 M M M MM MM M lu M M MM M M M M 'o 'o , , M M M M M M t 'o U M U 4-) M 10 U M M M M M 10 U U -1-1 -1-1 M 10 M IJ IJ 10 4-) 4-) 4- U t 10 -1-1 10 M -1-1 M U t lu (I 'o t 'o U U 'o U 'o 10 1 0 u M 4-) 4-) 10 U 10 10 10 (0 M 4-) 4-) 10 -1-1 t -1-01 U U M 'o 'o , 'o 'o 'o u 10 u I 1 0 10 t U M 4-) U 4-) 4-) CO t 10 CO 4 .) U 4-) 4-) 4-) (o U U M (o u u 4-1 u 4-1 U U , u M 'o , u 4-1 U co Co . t

) U 4-) J 4-) t U U tj tj U (0 U 4-) U 4-) M t I MM MM 10 10 -1-1 4-) U 4-) U 4-) CO M 4-) M U 4-) 4-) U M 4-) 4-) 4-) U M U u u (I (I U 10 U -1-1 U 'o _ U M M U 4-) 'o .U . . .M .0 ,M u U10 CO U 4-) U U M U ,4-) M U 4-) 'j 'o u 10 1 10 10 u M 'o U 'o U M , 'o U U U U M 4-) 4-) M 4-)(0 (0 'o , 'o 'o U -1-1 -1-1 10 10 4-) -1-1 M -1-1 U 10 -1-1 U -1-1 M 'o 'o U 'o t 'ot 'o (o (o U Co - I I 1 10 10 1 m u U (I U u 4-) CO U U 4-J (0 4-) (0 4-) (0 U (0 CO M 4-) 4-) U 4-) 4-) U U 10 1 1 t 4-) (o Co M M.) Co M 4-) U 10 t U -'Il 10 U 10 M IJ 10 M IJ 10 U 4-) M u t M M lu CO U 4-) M M U U 'o 'o , 'o 'o M , U 'o 'o 'j M 4-) M M M M , 'o -1-1 -1-1 10 -1-1 U M (I U M M u M 4J M U M M M M M M M M M M 4-) U U . . . (0 4-) U 10 1 10 1 m P I u m u U M M M U M M M M 'o 'o M (M 'o M 1luo luo 4-) lu CO luo U (I M -10, -1-1 4-) 10 t -11, lu -11-01 1100 t luo 1100 t MM IMO (110 (M IMO 10 4-) 10 U m I I P U U 4-) M M (0 4-)M M 4-) M (I U (1 -1-1 10 -1-1 10 M (I (I (I (I M (I M (1 10 M U 10 M 10 4-) 4-) u 4-) 1 1 (0 m (0 4-) 10 u 10 m 1 10 u u 10 P u P 10 u 10 m 10 U M 4-) M , t U , t 'o 10 u m 10 10 4-) M (0 (0 (0 U (0 4-) 4-) 1 u m m I M 4-) M U U (0 4-) (0 M U Co M M u m I , , M -1-1 t u 4-) M 4-) 4-) -1-1 M 10 10 4-) M M 10 1 M 4-) M U 'o (I (I M U 'o M M t 'o U m m m t 110 IMO luo (Ul t , M , 4-) U 4-) (1 M (I M 'o 'o , U U M 4J U M m I u R MR 10 1 1 10 -1-1 U 10 m u m u m m U M 4-) M 4-) U M M U U M M U U 4J M 4-J U M 4-) M u 10 10 t I M luo M U M M M 4J (I U , 'o , 'o 'o U , , U 'o (0 4-) t (0 (00 M 'o M , 4J 4J 4J U U U 4-) U U U M , I U (0 U (0 M M CO U 4-) (o M M M ( (o U (0 u -IJ -IJ M U U M U U 4J M M M (o U t 4.) Co (o M 4-) M M M Co U U M U M10 10 t lu0 -11, u u m 4-) 4-) 4-) M M U 4-) M M M M U M M M M 'o10 4-) 4-) U 4-) M 10 10 M M 4-) 4-) M M , U 'o 4-) M M M M M M M M M M 10 10 M U 10 U -1-1 4-) 4-) 4-) 'o 'o U t U M M IJ 4-) U 'o M M U 'o , U 'o M , M U , M U 'o M M t 4J M 4J U t MM t luo 'o 'o (1 4-) M M M M 4-) M M , M 2 M t M 4-) 'o M 'o (' U M 4-) 10 M 10 U -1-1 M 4-) (' U (' 2 2 M 'o M 'o 'o 'o 'o 'o 'o t (I M 10 U U t I M 10 10 1 M M M M U ,M , 4-) 'o (o U (o U co 10 M 1 U 10 m u I -1-1 M I U 10 I 'o I U M M U m U U 10 1 1 1 10 10 4-) 4-) 4-) CO ,M 'o u u 'o M U M U 4J M U M 'o M 4-) , U 'o ,'o , U M U M (o M (o 'j 10 1 m M M U U 4J M 4J M 'o U ,U -1-1 'o , M , U U -1-1 10 m M 4-) U 4-) 4-) 10 m 10 10 10 M 4-) M M ,U M M U M UM 4-) U 'o M m 10 (I 1U 4-) 4-) (0 U Co 4.) M CO.) Co M 10 1 M (1 10 M U 10 m 4-) 4-) CO 4-) U M 4-) (0 U 4-) M M U 4J M M U M 8 U 4J M M M M M (0 4-) 10 M M 10 10 M 4-) M 4J M U M M f U 4-) M 4-) 4-) M U M 10 U M M (o M M -1-01 U -1-01 10 U 4-) M M t t U 'o M 'o t t , M M , U , M M 'o 'o 4-) U4J 4J 4J 4J 4J 4J 4J M U4J M U M 4J 4J m m

4-) U 4-) t 4-) 'o U M M 10 U U t 4-1 u M 4-) U M U M 4-) M M R M M 4-) U ,M t M 10 M t10 -'Il t t U -'Il M t 10 -'Il 'o 'o M U M U 'o M .(I .(I .(1 U 10o U

1010 110 luo M M 10 'o 'o 'o 'o M 'o M , , U M 10 m 10 m U 10 4-) M M U U 10 U -1-1 10 M U M U 10 t 10 lo - m M U M M 4-) 4-)(0 M 4-) U (0 U 'o M , M , M , U U 'o U M M , M (, U U , M , 'o 'o U (I CO M 4-) M 4-) 4-) (0 M 4-) M M M M M U M U U M M M M M 4J 4J 4J U M 4J M M 4J M M 10

P.

MICI 2019/070246 PCT/US2017/054997

III 4J U III 4J 4J -1-1 U M U U 4J 4J 4J M 4J U 4-) 'o , t ,'o M U t 'o 'o , 'o 'o U U t M , 'o U , U 10 10 U U 10 10 10 4-) U U M 4J M U U U U 4J M 10 10 4-) 4-) U 10 M M U 4J 4J (0 U 'o M , M 10 41 m U , M M M , 'o , 'o 'o U m co co M M 'o 'o . .

. co M 4J U M M (, 10 4-) 4-) U U M M 4J M 4-) -1-1 -1-1 -1-1 M M 4-) 4-) (0 u 'ot 'o U M U 'o 'o U M 'o 'o 'o 41 , 'o 'o M M 4-) M U t 4-) t 4J M M M 10 10 U U U (0 M 4-) M M U t 4_) U 4-) 4-) (o M (o -1-1 10 U M t 10 u U M 4-) U 4-1 M M U M 4-) M M t U M -1-01 U 10 -1-01 4-) 10 (1 M (I M U 10 10 M U 'o 'o U , 'o 'o 'o U U M 'o , , 'o U U 10 10 u I 1 10 104-) CO U U Co (o (o 4-) U 4-) 4-J 4-J (0 4-J u u m 4-1 4-) M U M 4-) M 4-) 4_) (o uj u4-) t U 4-) 4-) U M t lu (11 'o M U t 'o 'o M , 4-) 'o , M U I I 10 1 4-) M 1 10 10 -1-1 u m M M 4-) 4-) M 4-) 1 m 2 M u R m 4-1 (0 4-1 m (0 4J 4J M 4-) (0 U t 'o , , t M . . (' t U M 4-) t U M (o u U -1-i t M t M M M U M U 4-) M M 'o M 'o U 10 (1 M 4-1 4-) MM MM 'o U M , 'o M M u 4J M 4J U M M (0 u (0 U M M M 4-) M 4-) U 'o U 'o t U E 2 t M MM M M M M M 'o U t 4-) 4-) (0 U M 4-) (1 M 4-) U 4-) M 4-) M M 4-) 4-) 10 M M M t M 4-) (0 M (I 4J 4J U M (0 (o U M , , , , 'o 'o M 'o M 'j 10 co u -1-1 4-) 10 10 1 1 m U t U M 4-) 4-) U U M M U U 4-) u (I M 10 10 M U -1-1 4-) (1 U 'o M , t 'o , 'o , , 'o 'o t 'o u 10 1 10 'o , 'o 10 (1 M U U U -1-1 -1-1 10 10 -1-1 M U4-) (0 4-) 10 -1-1 10 t U 4-) M M M 4-) 1 1 u 10 1 10 1 1 m u 10 m u t 1 10 (0 u 'o M 'o 'o M , U U 'o U U 10 U U -1-1 U U U U M t U 4-) MU 10 U M U 4J U 4J 4-) U M 4-) U U 4-) M , , 'o M 'o M , 'o 'j M 'o U M M M M -1-i U 'o 'o 'o 'o , , 4-) 'o M 4-) -1-1 -1-1 4-) 4-) U 4-) t 4-) (0 U 4-) U (0 M (0 (0 4-) M (o U , M , M , U U 10 U M (I (o 4-) U U (0 (0 4-) (0 (0 CO CO M CO U (0 4-) 'o t U M 4-) U U U Co t U 4-) M t 4-) 4-) 4-) 4-) U U U M , M , , 'o M t M 'o t 'o U 4-) , M u U 10 10 U U M 4-) 4-) u U t t -11, 10 1 U M M M 4J U 4J M 'o 'o 'o 'o 'o M 'o , U , 'o 4-) U M 4-) U 4-) 4-) 4-) U 4-) M 10 10 4-1 4-1 10 U U M M M U M M -I- 1 10 4_) M CO 4-) 4-)

10 1 U M 4-) U M 10 U CO 4-) 4-) 4-) (0 o U , M , , , , U U 'o 4-) (o 'o t t 'o (1 10 t 4-) 4-) t 4-) 10 4-) m m m m m 4-) U M U tjM M ,4-) , , , M (0 4-) u M M M M 'o M t M 4-) U U M 4-) 10 m u m m 8 t MM M U 'o U M M 'o M U 'o M U M -1-1 t RM lu IMO -1m 4-) U CO (0 (0 4-) (0 U (0 U 4-) M CO 4-J CO 4-J U U -1-1 U M 4-) 4 u Co (o U (o M 4-) M U 'o U M (o (o M Co Uco 4-) 10 M 4-) M U 4-) M IMO M U U t U U IM 4) 4-) M 4-) M 10 M 10 10 1 u u 1 0 t IMO U 4J 4J 4J U M 4-) 'o M 'o , 'o U M 'o U , 4-) M M M 10 M t M 10 U U M M 4-) 4-) U 'o 'o I' 'o M M M -'-' t 10 4J U U M 4J 'o U 'o M 'o M , 'o , 'o'ot M , 'o , M (I 4-) 10 U U 4J M M U 10 U 4-) M M t t t m t M M 4-) 4-) U U M U M M M 4-) U M M M M M 4-)U M M M 4-) U -1-1 M -1-1 10 M 10 8 E M M M M 'o (' M 4-) M t 10 10 'o -1-1 U M m M u 4-) m U u 'o m U m ,(I M 4-) t ,M . U 'o 4-) . ,U U .MM U 4-) 10 MM ,MM t t ,M 4-) 'oo M 'j (0M , U 'o M 10 U 10 M -1-1 M M U I I I u 4-) 'o m M 'o M U M 4-) U M 4J M 10 u u U 4-) U 4-) 4-) m u u I 1 10 R u 4-) 4-) M'o M U 4-) U M M M , , 'o U (0 (1 10 'o 'o . . . U M U U M M M M U U MU m 4-) U t u 1 4-) 4-) M U t m U U U'o 'o U 'o u 100 IM M 10 U t RM (Ul t lu IMO u U M 4-) U 4-) 4-) M M 4-) t U M I M 10 4-) (0 M 4-) (0 4-) 4-)IM U , M 'o , U M , 'o M U 10 u M -1-1 -1-1 10 10 4-) M M 4-) CO 4-) 'j tj 'o U 'o 10 M U (0 4J U 4-) U M 10 1 u u u (0 U , , 'o M 'o 'o 'o 4-) 4-) 4-) 4-) U 10 M 4-) CO CO M M Co 'o M , t M M 4-) M t U U -IJ M M M 4J M (I , 'o , U 4-) M U M Co 4_) CO CO 4-) U U 4-) 4-) 'o M 'o M (0 U , , M M 10 U 4-) U t M 4_) CO CO CO CO 4-) CO 4-) M (o (o M U M 4-) 4-) 4-) M 4-) U 4-) U M M 10 10 M M M M U M M 4-) M M 4-) M 4-) t U (0 4-) U M M M

, M U U , 'o , M 'o 'o U M M , M , M U M U 4-1 M M 4-) M U 'o u m I t M f M UM 4-) IMMM MUtUM M t 4-) 4-) 4-) 4-) 4-) M -1-1 -1-1 4-) co co 10 10 (0 U U 4-) 4-) U (0 4-) M M M 4-) -1-J M -1-J U 'o 'o , , 10 t RM M M M U U U M 4-) M U M M 4-) M M IJ IJ t M 4-) 4-) M M -L-i t t M 8 U U 'o U t 'o 0 M 'o M R U U M 10 U M M -L-1 10 -L-1 u 4-) 10 M M M 4-) M U 4-) M M M M U U M M 10 j j j j M .M . . M (1 10 -L-1 M -L-1 U M M U (0 (0 u U 10 1 10 10 (' M (0 M 'o M U 10 4-1 M M 'o 'o U M M M 4-) 4-) M 4-) M10 1 1 10 1 1 10 (I 10 10 M , U 'o 'o M , M , 'o U 'o 'o 'o 'o U U U M U 4J 4J (0 (0 u co I M 4-) U M M 4-) 4-) M M U 10 10 M U 4-1 U u co M . . . . M M 4-) M 4-) 4-) U u (0 (0 M 'o 'o , 'o M 'o M t 'o t 'o U M 'o (0 CO 4-) U U M 4-) U M M 'o j U M 4J M M M U (0 (0 4-) 4-) M U (0 (0 4-) U (0 4-) M 4-) U Co Co (I (I (I M (I 4-1 U (o (o (o (0 4_) j M M 4-) 1 u 10 1 u 4-) E M MM E E 9 'o , , U 4J U U 4J IM(I IM M t U M U M 8 MM lu M 4-J M M 4-) M 4-) U M M u 1 0 1 0 1 u I (0 u u I I 'o 44J M U 4-J 4J 4J 4-) 4-) u , U U 'o U 'o U 10 -L-1 4-1 4-) 4-) 4-) M U M 4-) 'o , t t 4-) U 4-) U 4-) U (0 10 m m Co .1_) t R u t -t M U .1_) 4J 4J (o (o U (o M U 4-)4-) U 10 -L-1 10 (0 .1_) Co 4.) 4-) U Co 1-) 1 10 1 M 4J U U M t U U 4-) 4-) co u co m I 1 10 M (I U 10 u U U U M CO 4-) 4-) U (0 M .1_) 'o U , 'o U U M 4-1 4-) M 4-) u 1 10 m u u m m 4-) M U U (o U (0 4-) 4-) U 4-1 4-) 4-) CO U 'o 'o 'o U 'o m u (0 U U M 4-) M M t U M 'o t (I t (M M 'o M M 'o 4J 4-J 4-J U U U U 4J M 4-) t U , U , 'o U M I u t 4-) U 4-) M M (I (I (I (I U (I (I -L-1 U 4-1 u m m u M MM I' M M 'o U 'o 4-) M (0 4-) (0 M 4-) 4-) 10 U 'o U 4-) 10 1010 u 10 m (I MM 4-) 4-1 4-1 M I' o M 'o , U t 10 'o 'o 'o U (o 4-) 10 10 10 M m U 4-) 4-) 4-) 'o 'o U , M M M 'o 'o M M M U U 4-) M MM MM 4-) U U (o (0 (o t t M 4-) U 4-) M t 10 U M U 4-) 10 t M m m u M m (I M (I M U M , , , 'o U t 'o U U 4-) M 4-) t U M U 4-1 'o '10 1 u 10 4-1 U M M (0 10 1 10 10 u R u M M M U U U 4J M M M M U U 'o U 4J U M 4-)

uo rq P. 2

MICI 2019/070246 PCT/US2017/054997

4-) 4-) 4J u m u u (0 4-) (0 (0 (0 4-J 4-) (0 (0 u u m , t 4-) m t (0 u M U M 4J U M u u u 4-) (0 (0 m M 4-) (0 (0 U (0 (0 4-) U 4-) (0 (0 m m 4-1 m u 4-) (0 (0 4-) (0 4-) U M 4-) (0 U 4-) U 4-) U CO CO U CO U CO CO M 4-) 4-) U 4-) (0 (0 M (0 4-) M M U 4J U M U JJ M CO M 4-)(0 (0 4-) 4-) 4-) U 4-J 4-J (0 4-J 4-J M (0 4-) m u m u u m u m u u M 4-) U 4-) 4-) (0 U 4-) 4-) 4-) (0 M U 4-J CO JJ CO U U CO U CO JJ CO JJ M 4-) 4J 4J 4J U M U U 4-) M (0 (0 4-) (0 (0 4-J M 4-J CO 4-) 4-) (0 4-) (0 4-) 4J U (0 (0 4J CO U 4-) CO CO M CO CO JJ M U 4J 4J (0 u u m (0 u u m u m m u u u co 4-) JJ M JJ JJ CO (0 4-) U M M U 4J M M 4J 4J 4J M M 4-) 4-) 4-) (0 U 4-) U U U M 4J 4J 4J M U 4J m m m u (0 u M M M M 4J (0 4-) U 4-) U 4-) U (0 U 4J M U M 4-) (0 (0 u m m u m m u (0 4-) 4-) U 4-) (0 M 4-J M m m m m U (0 4-) (0 4-) U (0 4-) 4-J 4-) M 4-) U 4-) 4-J 4-J M (0 U M M 4J 4J U U M M 4-) m m m m u m u U U M 4-) U U U (0 (0 U M U 4J M M (0 4-) 4-) U 4-) (0 U 4-) 4-) (0 U M 4J U M M U M M U 4-) U 4-) (0 M 4-) 4-) 4-) M u m m m u u 4-1 4-1 j u m (0 u m 4-) U U 4-) 4-) u u (0 U M U M M M 4J 4J U U 4J 4J 4J m m u (0 (0 m 4-) U (0 (0 4-J (0 u u 4-1 u m m m u (0 4-) M U U 4-) 4-) 4-J 4-J 4-J 4-J M 4-J 4-) U U U M 4J 4J 4J M 4J 4J 4J M 4-J 4-J M M 4-1 4-1 4-1 (0 4-J (0 (0 4-) 4-) (0 4-) (0 4-) 4-) U U 4-) M CO 4-) M 4-) CO JJ U CO U CO 4-) u (0 u u m (0 U 4-) U 4-) (0 U (0 4-) .1-1 u m .1-i .1-i u j u co U M 4-) (0 4-) (0 (0 M U (0 M 4-) M U M 4-) M U M M 4-) (0 U (0 4-) (0 4-) M U U 4-) 4-) U CO CO CO 4-) -1-J U U M 4J 4J 4J M M (0 4-) M (0 4-) (0 M 4-) M -1-J U U CO U 4-) U U U U M 4-) 4-) 4-) 4-J U M U 4-J CO M JJ U JJ JJ JJ U 4-J 4-) (0 4-) (0 (0 (0 U 4-) u 4J 4J 4J U U M JJ M CO U CO JJ U CO U U M 4-) 4J M U M U U 4-) 4-) 4-J U 4-J M 4-) 4-) 4-) 4J U (0 U U (0 4J U M 4-) (0 u (0 (0 (0 (0 (0 (0 4-) 4-) U (0 M U 4J CO CO U JJ U 4-) U CO U U M JJ 4-) (0 U M M M 4J M 4-) M (0 4-) (0 4-) U (0 (0 U 4J 4-J M M M M U U M M M U U 4J M M M U 4-) 4-) 4-J U U 4-) 4J U M 4J U (0 U (0 U (0 u (0 m (0 m (0 4-) U U U U M 4-) CO 4-) M 4-) M M 4-) (0 4-) 4-) (0 U M 4J M U M u u (0 M 4-) 4-) (0 4-J M 4J 4J (0 U U M U U U 4J M M 4-) M (0 M U m co co 4-) -1-J U U U U U 4-) M (0 U (0 4-) U M 4J M M U 4-) (0 U 4-J U U M 4-) CO 4-) M M (0 U 4-) M U U U U U 4-) U (0 co u CO U CO 4-) U M U CO (0 4-) M (0 4-) (0 (0 4-) M M 4-) 4-) 4-) CO j co co CO 4-) M U 4-) 4-) (0 U M U (0 4J U 4J U U CO 4-) 4-) CO 4-) co m (0 M 4J 4J 4J M M M 4J 4J M 4J U M M 4J U 4J 4J M M u u U 4-) 4-) (0 4-) M 4-) 4J U U (0 (0 U 4J U 4-J CO U 4J M U u (0 M 4-) 4-) U 4-) (0 4-1 (0 4-1 u (0 4-1 J-j u u U U U 4J 4-) M U 4J 4J U M U U U U 4-) (0 M M 4-) M M M u (0 u 4J U 4J 4J 4J M M M U U U U U (0 4-) U M 4-) (0 M M (0 (0 CO 4-) 4-) 4-) JJ J CO U (0 4-) 4-) (0 M U 4-) (0 (0 4-) m m 4-) M CO CO U CO M 4-) (0 4-) 4-) U M U 4-) (0 4J 4J 4J 4J u m .1-i m u u m u u u u u u 4-) M M (0 (0 4-) 4J U 4J 4J u m m u u U 4J 4J (0 4-) M U U 4J M M U (0 4-) U (0 U M M 4J U (0 (0 4-) (0 M U (0 (0 U M M M U 4J 4J M U 4-J U (0 4-) (0 (0 (0 m u 4-) M 4-) 4-) (0 U U U U 4-) JJ JJ U J J M M M U M U 4J 4-) U 4-) 4J U 4-J M 4-J U 4-) 4-) U M U U 4-) 4J 4J 4J 4J (0 (0 (0 4J 4J (0 4-) U U u (0 (0 4-1 (0 u (0 4J U M M U M M U 4-) U (0 (0 M (0 u u u 4-) (0 M M (0 M 4-J 4-J U J U M M M 4J 4J (0 U 4-) U U 4-) M M U CO 4-) CO M JJ JJ JJ 4-) 4-) U 4-) (0 U (0 m m u u m m 4-1 (0 4-J U 4-J CO 4-) 4-) 4-) U 4J 4J M U 4J U U M M M u m u 4-) U 4-) U U U U (0 (0 4-) U 4-) 4-) U M M U M 4J m u m 4-J U U M 4-) (0 U M U (0 4-) U (0 4-) U (0 m m u u 4-1 m m co u u M 4J 4J 4J 4J 4J M 4J (0 U (0 4-J U (0 4-J 4-) U 4J 4J M M (0 4J 4-) 4-) 4-) 4-) U (0 (0 (0 U 4-) U CO 4-J M CO 4-J 4-J 4-) (0 4-) M 4-) (0 U U 4-) 4-) CO 4-) 4-J CO 4-J CO CO 4-J M (0 M (0 U U U U (0 4J M 4-) (0 (0 (0 U (0 (0 u u 4-J 4-J M M M 4J 4J 4-) U M 4-) M M U (0 4-) U 4-) (0 M 4-) JJ M U CO co j co U U (0 4-) 4-) (0 4J M 4J U M 4-J M 4-J 4-J M M M 4-) M 4-) 4-) U (0 u u M (0 M M CO 4-) CO U CO 4-) U M CO 4-) (0 4-) (0 4-) 4-) (0 (0 (0 4-) (0 U 4-) U U M CO U -1-J M M U 4J (0 U (0 U (0 4J (0 U 4J 4J (0 U U 4-) CO 4-) JJ U M U U JJ U M U U M 4J U U U 4-) 4-) U M M 4-) u u m 4J 4-J 4-J 4-J U U U M 4J U U U U (0 U (0 U M 4-) U M 4-) u m m m m m U U 4J U 4J U U U 4-) U 4-) 4-) 4-) (0 co m U 4-) CO U CO CO 4-) (0 U U U 4-) U (0 4-) 4-) M 4-) U CO co u m 4-) M M U 4-) M U U U M (0 M M 4-) (0 M M U M 4J 4J M M u (0 co CO M 4-) M 4-) 4-) 4-) U 4J M M U U M U M U M M M 4J 4J M 4J 4-) U (0 U 4J 4J 4J 4J U U U M 4-) 4-J (0 U 4-J JJ JJ U JJ CO CO CO M 4-) (0 M (0 (0 (0 U 4-) 4-) 4-) 4-J U U (0 (0 u u m 4-1 u m u m m M M U 4J 4J 4J M M (0 u u 4-) U 4-) 4-) (0 4-) 4-J M M U U U M U U 4J 4J M 4-) (0 4-) 4-) 4-) 4-) M 4-) m 4-1 J-j JJ 4-J CO CO 4-) 4-) 4-) 4-) 4-) (0 (0 U (0 (0 U M 4-) 4-1 m J-j J-j co co co J-j (0 4-) (0 4-) 4-) 4-) 4J JJ U M CO U U 4-J CO 4-J CO (0 4-) M (0 M M 4-) 4-) 4-1 4-1 u 4-J U J U M M (0 4-) U 4-) M M U 4J M M U (0 (0 4-1 u u (0 (0 4-1 4-1 (0 (0 M U (0 M U 4-) U 4-) M M 4-) CO M 4-) CO CO CO CO co m (0 U U U U M 4-) U M (0 4-) (0 M 4-) U 4-) CO CO 4-) 4-) J-j co co m u u J-j m U 4-) (0 4-) M (0 (0 4-) U (0 M 4-) U M M 4-) 4-) 4-) CO M M U 4J U (0 U (0 (0 U m m (0 (0 (0 4-) U M CO 4-) M u u .1-i u .1-i u u u 4-) M U (0 4-) (0 M (0 (0 u 4-) U CO 4-) CO CO CO M U (0 U M M (0 4-) (0 4-) (0 M 4-) CO 4-) co co co 4-) 4-) 4-) 4-) U U U (0 (0 (0 M (0 4-) 4-) 4-) U CO M 4-) U CO CO 4-) M 4-) U 4-) U (0 (0 U U U M U (0 (0 U (0 4-J M 4-) U CO U M 4J JJ U U M (0 4-) 4-) (0 4-) (0 4-) M U (0 U 4-J 4-1 u u u m u u m m m m U 4-J 4-J 4-J U 4-) (0 M 4-) U 4J M U 4J 4J M U U M U 4-J U M M U M U 4J M (0 (0 M M 4-) (0 4-) (0 M U U 4-) 4-J (0 U 4-1 u u u m u m j u m u 4-) U M (0 M U M (0 4-) (0 (0 4-) 4-) JJ U CO CO U M JJ M (0 U (0 4-) M 4-) U M 4-) 4-) U 4-) (0 (0 CO m co co CO U U 4-) M U U CO M 4-) (0 4-) U (0 4-) U (0 (0 4-) 4J M U M M M M M 4-) 4-) M 4-J U U U U (0 M 4-) (0 (0 4J 4J (0 (0 (0 4J U M M U 4-) M CO 4-) U CO CO 4-) (0 4-) 4-) 4-) 4-) U 4-) 4-) U (0 U M 4-) M U 4-) M U CO M 4-) U U (0 (0 (0 (0 m (0 (0 4-) U U 4-) 4-) M CO CO 4-) M 4-) (0 4-) (0 M 4-) (0 (0 (0 M CO U M 4-) CO CO CO M 4-) 4-) U 4-) U 4J U (0 U (0 (0 (0 M M (0 4J (0 (0 U M M 4-J J-j u m (0 4-) (0 U (0 U M 4J M U M 4J M 4J U 9 4J U 4J (0 u u

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co m J-j co m J-j J-j co co u m J-j co J-j m J-j u u J-j co u J-j m u m m m u u J-j m J-j m J-j m J-j J-j J-j J-j m m J-j m m m m m m u u m m co u u m u m u u m u m m u m J-j m u u J-j m m m u m J-j J-j J-j J-j m co J-j co m J-j u J-j u co co co co J-j m co J-j m m J-j m co u m u u co co J-j J-j m J-j m m u m m u co m co u co J-j J-j u co m m J-j m J-j u m J-j co m u co co u J-j co co m m m u m m m J-j m m u J-j J-j u m u co co J-j u co m m J-j J-j J-j u J-j u J-j J-j u J-j J-j u J-j co J-j J-j J-j J-j u co co u m m co m m J-j co m J-j J-j J-j co co J-j co m m u J-j J-j J-j J-j m m J-j m co co co J-j J-j J-j co co J-j u J-j co co co u J-j co u J-j co m co u co co J-j m u co co co m J-j u co J-j m J-j co J-j m J-j J-j J-j co m u u co u co co m m u J-j J-j m u m m J-j co J-j co co u u m m J-j co m u co co m J-j m m co co co co m J-j J-j co m co m J-j u J-j co u m u m co u J-j co co u m J-j u u m J-j m co u J-j u J-j co J-j u u m co m u m u J-j co u J-j m m m m J-j u m m m u m J-j m m m m 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m m m m m m u J-j m u m J-j u m J-j co J-j u m m u m m m u J-j m J-j J-j J-j m J-j m m m u m J-j J-j m J-j m m u u m m u J-j J-j J-j J-j u m J-j J-j co co m co m u J-j J-j J-j m u m J-j co u co J-j J-j J-j co co J-j m u co m u m m J-j u m m J-j J-j u m J-j J-j m u u J-j u m m m u u J-j m J-j J-j m m J-j m m m m m m m u m J-j u m u J-j m co m co J-j J-j co u co co J-j co m J-j J-j J-j u J-j co J-j co J-j co J-j u u J-j co J-j m m J-j co co m m co J-j co J-j co co u co co J-j u u J-j J-j m u u m u 4-1 m m co co J-j J-j co J-j co J-j co m J-j m u m co u J-j J-j u m co J-j co m u m co u J-j J-j m u J-j co m u m m m m m u m J-j J-j m J-j m m u J-j J-j J-j J-j m J-j m J-j m u m m u u co co J-j J-j m m co J-j co m m co u J-j J-j co u J-j u m J-j J-j co J-j J-j co u u m co co J-j J-j m u co m co m m m J-j co co m J-j co J-j co co co J-j m m J-j u J-j m J-j J-j u u co co co co J-j u m co m J-j m 4-1 4-1 u co u m J-j J-j u m m co co J-j co co J-j m m m co u u J-j m m co u co J-j m co u J-j m u 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MICI 2019/070246 PCT/US2017/054997

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u m M U M 8 8 M M 4J M . . . . . M , M M 'o 'j I m I I u m 10 10 4-) 10M 1 1 u m 10 M M M 4-) U M 4-) 4-) M 10 4-) -1-1 10 10 M (I U (I U M 4-) R M , U M , M M 4-) M U 4-) 10 U 10 M M -1-1 M M U 4-) 4-) 4-) 10 M M U U M M 4J 'o M 'o U M , M 'o U , 10 1 4-) 4-) (0 4-) (0 (0 M M M (0 U U 4-) U CO U U M 4-) U U (o M U (o M 4-) U 4-) 4-) 4-) 4_) Co 10 u m u m t I I I u (o u m u (0 U 4-) 4-) (0 4J 4J M M M M 4-) U U M 4-) M -I- 1 10 -1-1 co u M U , 'o M M RU4J 4J U4J M M U 4-) U 4-) M M U M 4-) M U M M 4-) M M m 'o , 'o , 'o M U , M M 'o 'o U 'o 'o , 'o 'o , m M M 4-) M M U M (I m 10 10 u u U M M M 4-) M 10 M U -1-1 10 U U M -1-1 4-) 'o U M , , 'o (0 (1 (1 U , , 'o , 'o 'o 'o 4-) 4-)M4-) 4-) M U U , 'o , M 'o , , U , U M 'o M M 4-) -1-1 U 10 -1-1 M 10 U CO U M (0 U 4-) M 4-) (0 (0 4-) U 4-) 4-) 4-) u 10 m 4-) U M m 10 4-) M 4-) M 10 10 M U 4-) 4-) M 4-) M -1-1 10 M -1-1 t -1-1 M U 4-) M (I M U 4-) CO M m I M U 4-) M t 4-) M U -1-01 M 4-) -1-1 M -'Il 4-1 10 M 4-) U 4-) u u m 10 I-) (I U , M M U , M , , U 'o 'j 'j M , , 'o U , , 'o 'o , U 10 M 4-) 4-) U M 4-) 'o 'oM M , U 'o , , , M U U -1-1 8 t t 'o 8 8 M t 4-) 4-) 4-) U t m m u u m m u m 4-) U , 4-) M M 4-) M U U m U 4J U M M M M-(, U M 4J 4J U M 4J M M 'o 'o , M 'o , u u u (, mo U 10 m u M 1010 (1 'o u m 'o M 4-) 4J 'o 4-) U U U U U U M U U U M 4-) M (Ul (I M 10 u u M , u 'o ,M 'o M U 'o U 'o , M , U , M 'o 10 1 M j j j t M 4-) 4-) (11 U M 4-) 10 10 10 -'Il U U 4-) luo 4-) R t -11, M MM M M 4-) M 4-) 4-) 4-) 'o 'o M U U 'o 'o (0 4-) (0 'o U -1-1 8 (1 (I U U M U 10 U M (I 10 10 1 m u 10 u U M M M U CO 4-) u m I R m 4-) -1-1 U M 4-) M u U IM m u 10 M U -1-i m u u 4-) U 4-) M U M M 10 U 4-) 4-) (0 u U U M 4-) M M 4-) M M U m u U 'o , , M M , 4-) M U 'o , (0 M 'o U 4-) u I m m u I U m M U M , m u M M 4-) (0 4-) M U (o M U M U U M 4-) (o (o 4-) M U 4-) M M U t co 4-) CO M U M U u u m m m M M M M M 4-) 10 10 M U t M U 'o U M , U M M U U 4-) U 10 10 U 4-) 4-) M M M 'o 'o 'o , , M , , 'o 'o M M M M 4J 4J M , (0 (0 U U CO M 4-) 4-) 4-) 4-) (0 U U 4.) 4.) CO M U 4-) 4-) M 10 4-) 4-) U M 4-) M -'-' M U U M 4.) t U Co M U U 'o M M 'o M , 'o 'o U 'o U t t 'o ' 'o R U ''o U M 'o U M M 4-) 10 10 -1-1 10 M M 4-) 4-) 4-) 4-) M U -1-14-) U U 4-) 4-) 4-) M 10 'o M , 'o M , U 1 1 4-) M 'o U 'o U 'o (o I-) M 'o M M U U U , I 4J M 4J M 8 M U M M U U (0 (0 CO 4-) CO 4-) 4.) U 4-) M (0 4-) U U M M M M U U M U (0 u U U M U U 4-) M M M M 4-) 10 t 4.) 4_) t 4-) t U 4-) M M M 4-) M 10 U 4-) 4-) M , 'o U U 'o U U . . . M -1-1 10 10 'o 'o M U , 'o 'o 'o 'o -'-' 'o 'o U U (' U U U U U (' U u 1 10 u 10 M 4J M 4J M M M M M M I M 10 1 1 10 10 U 1 10 10 M U 4-) 10 4-) 10 M U 10 M (0 (I U (0 u M U M 4-) 4-) U 4-) U M 4-) U M U M 4-) M 4-) U M 10 4-1 10 10 t co u 10 10 u (0 u , U 'o , 'o 'o , M 4-) 'o U 'o U 'o 1 10 m I u m U (0 CO 4-) U 4-) (1 U -1-1 M 4-)M t CO CO U 4-) U U M U M M M t 4J M (I (I 4J U M M m u I u t UU U M M M 4-) M 4-) 4-) 4_) (o U (o 10 , (0 M M U 10 m 4-) U 4J M M U'o t 'o U M 4J U -IJ M , , R g M M M M m m m m m u 4-) U 4-) m m u 10 u R M 4-) M M U M 4-) M (1(1(1(lmmtllooluolloOMMUMMMMR u (0 M M 4-) M M U (0 (0 4-) U 4-J 4-J U M 'o 'o U M 'o , 'o m u M M M 4-) 4-) U U M 4-) U U t 10 4-) CO CO 4-) M U 4-) u m (o 4-) M U 4-) 4-) 'o t 'o U 'o 'o 'o U U M (I U 'o t 4_) 'o , 4-) , M , M 10 m m 1 10 10 10 U U U 4-) M M M t M t M 4-) M M M (I IMO U M u m m 1 10 10 m (I I I 'o M , 'o 'o 'o t U 10 1 U M 4-) U 'o U 'o 4-) u , 'o t 'o t M U (I 10 U M M M M U 4-) M M M -1-1 U M _,_, M 'o 10 10 M 4-) U 10 4-) 10 10 M 'o 'o , M 10 'o M 'o U (, 'o M 4-) (1 M UU 'o M M ,M 4-) U M t U -1-01 10 M -1-1 M 4-) M , ,

10 U 'o M 1 'o 10 'o U M M ,10 10 t 10 u R 4-) 4-J 10 u u 10 1 u 10 4-) M U 4-) M M (I M U m m u m u u 4-) (0 (0 (o M 1 10 R t m 'o M -1-1 10 4-) M 4-) M M MR 4-) 4-) 4-) 'o U 'o M U , 'o 'o U M t 'o M U t R U ' M I (I t M "Oo um 4-) U M M 10 M M 10 4-) u u u U M M 4-) M t (M u 10 10 t U M 4J U 4-) M 4-) CO U , 'o Co U Co R (o M U 4-) u 1 10 10 10 4-) M M M (0 4-) .) 4- ) Co Co U U U 4-) CO CO U 4-) M (0 'o U M 4-) 4-) 4-) U (o t 4-) 4-) U U U 4-) 4-) CO U t (00 (.0 U CO 4-) M M M (I M 'o 'o M M ,

10 t 4-) u M M U U C ) .) M (o U M U 10 1 M M M t M 4-) U u u u U M M 8 M 4J M M M t U M t M 4-) U U U m 'o U M M 'o 10 M M M 4_) U 4-) 10 U U M M 4-) M M 10 M U U U U (I M U M U M M U (Ul 'o U 'o 'o U t 'o 'o m 1 4-) (1 U m m m 1 -1-1 10 M t M 4-) 4-) 4-) , 'o m 10 1 10 10 m I t U M U 'o M 'o U 'o 'o , U U M (I U (I (I U M (I (I M 10 M 4-) 'o 'o U M8M4J M 4J m u u u I u 10 10 t US u u u1.) m u I u u R I U U CO 4-) M U U M M U M 4-) 4-) M U M U M U M 4-) M M U4J (0 (0 M 4-) 4-) 4-) (0 U M U U (0 4-) U M U 10 M 4-) , 'o , M U 'o 'o U U u (0 4-) U 4-) U U M t U 10 4-) 10 -'Il U 10 'o 'o 'o M , 'o M (0 4-) M 4J M M m 10 4-) M U U U M U , m m M U M U U 10 4-) M M M 4-) M M M 10 M M U 4-) U 'o 'o 'o M 4-) M -1-1 10 M U -1-1 10 (110 luo 4-) M 4-) (0 E t t M RM M U , U , 'o M , M U , , 'o , 'o M 'o 'o , , M ,

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MICI 2019/070246 PCT/US2017/054997

u u 4-) 4_) U U U U 4-) m u 4-) 4-) U U M M M 4J M M M M 4J 4J M M (o(o (o M (o U t u u u u u u m u U 4-) 4-) 4-) 4-) 4-) 4-) 4-) 4-) 4-) 4-J U 4-J u 4J 4J U U 4-J 4-J 4-J U 4J U 4J 4-) 4-) 4-) U JJ JJ M 4-) M 4-) U 4-) (0 U u u 4-1 u m m 4-) U (0 4-) 4-) (0 4-) 4-J U U U 4J U 4J 4J 4J 4J 4-J 4-J U U U 4-J U U U M M M 4J M 4J 4J 4-) 4-) M 4-) 4-) 4-) 4-) U U (0 4-J M 4J 4J M 4J 4-J 4J U U 4J 4-) U 4-) U 4-) 4-) M U CO 4-) U U (0 4-) M U 4-) U 4-) 4-) m (0 M M 4-J 4-J 4J M U 4J 4J M 4-) U U 4-) 4-J (0 (0 co co U U 4J M (0 4J U M U U U U U 4-) (0 U 4-) JJ JJ u u U U 4J 4J 4J U 4J 4J 4J M U U U 4-) 4-) 4J 4J (0 U 4-) U U U 4J M M 4J 4-J U CO 4-J U 4-J U 4-) U M (0 M 4-) 4-) U 4-1 4-J 4-J 4-J U 4-J CO U 4-J 4-) (0 (0 4-) 4-) (0 4-) 4-) 4-) U U U 4-) 4-) U u co U M M M U 4J 4J U 4J U U M M 4-) U U M 4-J 4-J 4-J 4-) 4-) U 4-) 4-) U (0 M U (0 U 4-) (0 M M M 4-) JJ JJ U J 4J M U M 4J 4J U M 4-) 4-) U 4-J U 4-J U 4-J 4-J M U 4-) CO U 4J 4J 4J U M 4J 4J 4J U M M 4-J 4-J m U U U M 4-) 4-) 4-) U M U U U U U U 4J M U 4J 4J U 4-1 U 4-J U U U 4J 4J 4J M U U M M M M 4J U U U 4J 4-) M M U (0 4-) 4-) U U 4-) 4-) 4-J 4-J U CO 4-J 4-J M U 4-) 4-1 4-J U 4-J 4-J 4-J 4-J 4-J -1-J M M U M 4J 4-) U 4-) 4-) 4-) U U u U U M 4-J CO 4-) 4-) 4-) (0 4-) 4-) 4-) 4-J CO CO M 4-J 4-J 4-J 4-) U (0 4J 4J 4J U U U 4-J U 4-J 4-J M U U 4-) M M 4-) 4-) 4-) 4-) 4-) U 4-) U CO U 4-) 4-J U 4-J CO M M U 4-) 4J 4J M M M 4J 4J 4-J U U 4-J u U 4-) 4-) 4-) M (0 4-) M (0 4-) U CO CO CO (0 M 4-) U U 4-) M u 4-) U U 4-) CO CO 4-) U 4-) U U U CO U 4-) 4-) M 4-) M U (0 (0 4-) u U U 4-) U 4-) U 4-) U 4-) U 4-) U U 4-) (0 4-) M U CO 4-) U u u u (0 (0 m u 4-) U 4-) 4-) 4-) U 4-) 4-) u m 4-) 4-) U 4-) (0 4-) (0 4-) CO 4-J U 4-J U 4-J 4-J U M 4-) U 4-) 4-) 4-) U U U 4-) 4-) CO U 4-) CO 4-) CO M M M M (0 (0 U (0 4-) U 4-) CO 4-) U M U U U U 4J U 4J U U U 4J U U U M U 4J 4J U 4J 4-) M U U M U M 4J U U 4J U 4J U U 4J (0 U 4J 4J U 4J U U 4J 4-) M U 4J 4J M M M 4-) (0 4-) 4-) U 4-) 4-J (0 M U 4-) 4-) 4-) (0 4-) U 4-) 4-) JJ U JJ 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J-j co J-j m u J-j m J-j J-j co J-j u m m u m m u J-j m J-j J-j m

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u co co co J-j u co J-j J-j J-j m u m m J-j m m u J-j J-j u m u u m J-j u m m J-j J-j m m J-j m m m m J-j m m m m m u m J-j u co u m u co J-j J-j m co u J-j co co J-j co J-j J-j m u J-j co m m u co J-j u J-j m co co m co u J-j m m m u J-j u co m co m m co m J-j co u co J-j m J-j co m co m co m co co m m m u m m J-j m m m m J-j m J-j J-j co co co m J-j u m m J-j J-j co co m u m m m m m m J-j m u m J-j m u m m m m m J-j m J-j u m m J-j m J-j u u m u m u u u co co u m u J-j m J-j co J-j co u J-j m m J-j u u co co co co m co u J-j u co u co J-j m J-j u m u co J-j co co m J-j co co co co co J-j J-j co m J-j co m m m m m u J-j m m m m J-j m m m m m m m m m m u m m m m m J-j u m co J-j co J-j m u m u m m m m m m u m m J-j m m m J-j u J-j u m m J-j m m m m J-j co co J-j m m m m J-j J-j u m m m u u J-j m u u m m m m m m m m m m m co J-j J-j m J-j u J-j J-j co u J-j m m m u m m u u u m m m m m m m J-j m m u m u m m u J-j u u m J-j m J-j u m m m m m m u J-j m m m m m m u m u J-j m m m u u m m m 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co m J-j m u J-j co J-j J-j m co co co J-j J-j u u m co J-j m co co m co J-j u m m u J-j m m m J-j u co m co u m J-j co J-j J-j u u co u m J-j u J-j J-j co u m co m m J-j J-j m J-j J-j m J-j co J-j m m m m J-j J-j J-j m m u m m J-j co m J-j J-j J-j J-j J-j J-j co J-j J-j co co co m u J-j u co m J-j co u co co J-j m m J-j u co J-j J-j J-j u u m co J-j co co m co co m m co co co u J-j J-j J-j m J-j co m co co J-j m J-j J-j u co m u J-j J-j m u J-j J-j u J-j J-j m co m u m u u J-j u co m m u m m J-j m u J-j J-j m m u m m J-j m u J-j m u u J-j J-j m u u u m m u J-j J-j J-j m m u m u u u u u m m m m m u m J-j m J-j co co co u J-j m co J-j m co m co u J-j co co J-j u m co J-j m J-j J-j u J-j J-j J-j 4-1 4-1 co 4-1 4-1 co J-j co co co m u m J-j co u J-j u J-j m u J-j J-j m J-j m u m J-j m u J-j m m m J-j m m m m u m m m m J-j m u co J-j m J-j J-j co J-j m co m J-j m co co J-j u J-j u u co co J-j J-j m u co co co m J-j u m J-j co J-j u J-j co co m m u co u co co m co J-j u m co J-j m m u J-j 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Table 8: Forward and reverse primers for amplifying modified sequences

Description SEQ ID NO: Sequence (5'to 3') KOPASchr3_1087 Verification F 334 ATCGGCAAAGATGAAGCGAC

KOPASchr3_1087 Verification R 335 GCTGGACACTTCTGAGCTCA

KOPASchr4_0584 VerificationF 336 ACTTGTCAGGACGATACGGA

KOPASchr4_0584 Verification R 337 CCGGTCTCCCTGGAAATAGA

KOPASchr3_0076 Verification F 338 GCGAGGTCCTTGTCAATGAG

KOPASchr3_0076 Verification R 339 ACAAGAACTCGGGCTCCTTT

KOPASchr3_0691 Verification F 340 TTGCAGCGCTCCATAATGTC

KOPASchr3_0691 Verification R 341 GCTGATTCTGAGAACGCTGG

KOPASchr3_0303 Verification F 342 GCCATTCTTCGGTGCAGTAG

KOPASchr3_0303 Verification R 343 TAGAGTTGTCCCAAACGGCA

KOPASchr3_0815 Verification F 344 CGTGGTTCTCGAGGCTCTAT

KOPASchr3_0815 Verification R 345 GGAGTTGGAACGTCGTAGGA

KOPASchr3_1157 Verification F 346 AGTTGTCCGTCATTAGCCCT

KOPASchr3_1157 Verification R 347 TGTTCCCTTTCGGCTAGACA

KOPASchrl-4_0164 VerificationF 348 ACGGTTGAGGGCATTACGTA

KOPASchrl-4_0164 Verification R 349 TTGTCTTCCACCCCTTCGTT

KOPASchr3_0979 Verification F 350 GGTTGGCCTTGGACATTGTT

KOPASchr3_0979 Verification R 351 TGCTCTTCGGTACTCATGCT

KOPASchr3_0803 Verification F 352 TTTGGCCATGCTGAGCTTTT

KOPASchr3_0803 Verification R 353 AAGCCCGATCACTTGCATTT

KOPASchr3_0394 VerificationF 354 CACCTAATGTTTGGCACCCC

KOPASchr3_0394 Verification R 355 ATCCCAGACTGACATCGCAA

KOPASchr2-1_0366 Verification F 356 CCGCCAGAAATTCATGCCAT

KOPASchr2-1_0366 Verification R 357 TCGTTTCACTGTACCATGCA

KOPASchr3_0842 Verification F 358 ACCAGTCCGCATTTTCACTG

KOPASchr3_0842 Verification R 359 GTGGACAGCTGCAATCGTAG

KOPASchrl-3_0195 VerificationF 360 CAACTGGGAAGCCTGCATTT

KOPASchrl-3_0195 Verification R 361 CCTTGCATATCCGTTTGCCA

KOPASchrl-4_0052 VerificationF 362 GGAGGTTCAGGAGCAGGAAT

KOPASchrl-4_0052 Verification R 363 CGGTTTCATCTGTTGCCTCC

KOPASchr2-2_0057 Verification F 364 GTCGCCCATGTTCTTTCGAT

KOPASchr2-2_0057 Verification R 365 CAAACAGGCTGGAAACCACA

KOPASchrl-3_0150 VerificationF 366 AATCTCCACGTTCAGTTGCG

KOPASchrl-3_0150 Verification R 367 TCATCCCTTGAAAACCCCGA

KOPASchrl-3_0221 VerificationF 368 TTGTGGAGGGAGATTCAGGC

KOPASchrl-3_0221 Verification R 369 AAGGTAAGGAACGTGCTTGC

KOPAS FragD_0022 VerificationF 370 GTTCTACTGTTCACGTGCTCT

KOPAS FragD_0022 Verification R 371 ACCGGTTAGAATACATGCTGC

KOPASchr2-1_0159 VerificationF 372 CGAAAAGAAGCTGGACTCCG

KOPASchr2-1_0159 Verification R 373 TTCCATCGTACGACCAGTGT

KOPASchr2-1_0326 Verification F 374 AGCGATGAGGCCAACAGTAT

KOPASchr2-1_0326 Verification R 375 TGTCCAGCCCAAAAGACTGA

KOPASchr2-2_0056 Verification F 376 CTCCTGGGGCTCGTACTAAG

KOPASchr2-2_0056 Verification R 377 CCTCAATAACGACGGCCTTG

KOPASchrl-4_0611 VerificationF 378 CCTTTTCCTGATCAGTGGGG

KOPASchrl-4_0611 Verification R 379 TGTTGGGGAATGAAACACGA

KOPASchrl-1_0274 VerificationF 380 GAAGGACGAGTAGGGTTGCT

KOPASchrl-1_0274 Verification R 381 TCCTGATCTGGCTCGTTTGT

KOPASchr4_0834 Verification F 382 ACCTCCAACTCCTGAAAGCA

KOPASchr4_0834 Verification R 383 CCTCGAGTCTGGGCTTTACA

KOPASchr3_0896 Verification F 384 GGAGAGATGCCAGACCAAGT

KOPASchr3_0896 Verification R 385 AGCCTGTTCTACTGCATACGT

KOPASchr3_0561 Verification F 386 CCATTTCTTGTACCCTGGGC

KOPASchr3_0561 Verification R 387 GCAGAAAAGGCGCGAATTTC

KOPASchr3_0633 VerificationF 388 GGGAAAGGATGTGGACCAAC

KOPASchr3_0633 Verification R 389 TGGCCAAGAGTGTCCAATTG

KOPASchr4_0013 Verification F 390 TAACAGATGGCGCACGTAGA

KOPASchr4_0013 Verification R 391 CCTTGCGTTCCCAGGTAAAG

KOPASchrl-1_0379 VerificationF 392 TGTGGTATGGTTTGGGGCTA

KOPASchrl-1_0379 Verification R 393 ACTCCCGTTCCTCCATGTTC

KOPASchr2-1_0172 Verification F 394 ACGGTACAAAAGGCGTTTCA

KOPASchr2-1_0172 Verification R 395 AGTCAAACTCGGTGGTAGGT

KOPASchr3_0866 Verification F 396 CGGTTATCATGTGCCTGCTC

KOPASchr3_0866 Verification R 397 ATGTTGCTGCTCCGAAATCC

KOPASchr3_0299 Verification F 398 GATCTGCTGGCCTTGAGAGT

KOPASchr3_0299 Verification R 399 CTATGTCCTGGTGTTTGCCG

KOPASchrl-4_0251 VerificationF 400 GCCAATGATGATCTCGCAGG

KOPASchrl-4_0251 Verification R 401 GCCTTTGATATGCCGTCGTT

KOPASchr4_0874 Verification F 402 TCGAGTAATGCTTCCCACCA

KOPASchr4_0874 Verification R 403 AGCTTTCACAACAGCGATCG

KOPASchr3_0513 VerificationF 404 TGATTGCTTCTGGGTTGCTG

KOPASchr3_0513 Verification R 405 CAAAACCGGCGTAAAATGGC

KOPASchrl-1_0127 VerificationF 406 TTGTGCTGCATCTGTGTGAG

KOPASchrl-1_0127 Verification R 407 AGCCTACAAGTGGTTACAGGT

KOPASchr4_0686 Verification F 408 GGAAACCGACCAGCCTAAAG

KOPASchr4_0686 Verification R 409 AGTCGCACCAGGTTATCACA

KOPASchr2-2_0159 VerificationF 410 GGAAAGCTGCCCAGAAACTC

KOPASchr2-2_0159 Verification R 411 TGAGAGGATTCGTTGTGGCT

KOPASchr3_0388 VerificationF 412 CTATGTCGAAGTAGCGGTGC

KOPASchr3_0388 Verification R 413 AGAGTGGCACTGCTATCGAA

KOPASchr3_0419 Verification F 414 CGTACAAACTTGGCAGCTGT

KOPASchr3_0419 Verification R 415 GCTGTGTTGTAAATTCCGGC

KOPASchrl-3_0258 VerificationF 416 ACAACCCGGAAGACAACTCT

KOPASchrl-3_0258 Verification R 417 TGTCGTTGCCTTCCCGATAT

KOPASchr4_0913 Verification F 418 GAAGATGGGAGAGGGTGCTT

KOPASchr4_0913 Verification R 419 CTTGTTGACGACGGTAGCAG

KOPASchrl-1_0066 VerificationF 420 CCCTAGTCTCGTTCGAAGGG

KOPASchrl-1_0066 Verification R 421 GGCACAGCAGGTTTTCGTAT

KOPASchr2-2_0310 VerificationF 422 GGAGATTCTGATGCTACCCCA

KOPASchr2-2_0310 Verification R 423 TGGAGCCATCAGATCAGGAC

KOPASchrl-3_0261 VerificationF 424 CCTGTTCTTGCAAGCCTTCA

KOPASchrl-3_0261 Verification R 425 TAAGACATGCGACCACCAGA

KOPASchr2-1_0546 Verification F 426 CATGGCCAATGTCGAACTGT

KOPASchr2-1_0546 Verification R 427 AGCTGGCTGAAAAGGTGTTG

KOPASchr2-2_0398 VerificationF 428 CTCAGTGTTGGAAAGCACCC

KOPASchr2-2_0398 Verification R 429 TAGGGAATCTTTGGTGGCGT

KOPASchr4_0835 VerificationF 430 GGAACCTAGAGCGAGCAACA

KOPASchr4_0835 Verification R 431 CAGGCTCTATTGTCGACGTG

KOPASchrl-1_0491 VerificationF 432 GGAGGTGATGACAATGCCAC

KOPASchrl-1_0491 Verification R 433 CTGTGAAGCTCCTCCTACGT

KOPASchr2-1_0447 Verification F 434 GGACACTGCTGGACAAGAGA

KOPASchr2-1_0447 Verification R 435 TACTGACGCCGAAGAGCTAG

KOPASchrl-3_0053 VerificationF 436 CCGATCGCAAAATAGTGGCA

KOPASchrl-3_0053 Verification R 437 GTTGTGGTTGTATGCGGTCA

KOPASchr3_0200 Verification F 438 CAATAACTCCACTGGTGCCG

KOPASchr3_0200 Verification R 439 TCGTTATACTCCAGCGTGCT

KOPASchrl-3_0105 VerificationF 440 GGGCTCAAAATCTGGAACCA

KOPASchrl-3_0105 Verification R 441 CAATGCAGTACTCACCGGTG

KOPASchr3_0635 VerificationF 442 AAGCTGACGACCCCTTAGAC

KOPASchr3_0635 Verification R 443 CTATCGTGTCTGGGCTGCTA

KOPASchr4_0503 Verification F 444 AAGGAGATTGCCGCAACTCT KOPASchr4_0503 Verification R 445 GTGGAGTCAGAGTCGAGAGG

KOPASchr2-1_0569 Verification F 446 CCCAGCTTTTATACGGCTTGG

KOPASchr2-1_0569 Verification R 447 CAGCAAAAGCTCGTGATCCA

KOPASchr3_1223 Verification F 448 TGCGGGTAGTCGATTGATGT

KOPASchr3_1223 Verification R 449 TCACGTATCTCAGCAACAGGA

KOPASchr2-1_0597 VerificationF 450 GGACCTAGGAAATACGCCCA

KOPASchr2-1_0597 Verification R 451 ACTCCAGTTCCACAAGTCCA

KOPASchrl-1_0327 VerificationF 452 ACTGCCAACCGTTTACTCCA

KOPASchrl-1_0327 Verification R 453 GCGCGGAAGATTAAAGTCGT KOPASchr2-2_0380 VerificationF 454 TTGGACTCGATCGATGAGGG

KOPASchr2-2_0380 Verification R 455 TGATGACTTCCAAGATGCGC

KOPASchr3_0928 Verification F 456 TCACCTGGAGCAACTGATGT

KOPASchr3_0928 Verification R 457 GTTTGGTACGCTTGTAGGCC

PAS-chrl-3_0184 VerificationF 458 GATGAGCAAGCATCCATTCA

PAS-chrl-3_0184 Verification R 459 AAAGACAGGAGCGTGAGCAT KOPASchrl-4_0289 VerificationF 460 CTCAACTTCGCTTGCCCTTT

KOPASchrl-4_0289 Verification R 461 TGGGAAACAGAACGATGAACT

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 CN o 'T 0 110 CN o 'T 0 o CN o 'T 0 Q0 0 CN o 'T 0 Q0 CN o 'T 0 tD CN o 'T 0 .o 0 0 H CN CN -(Y I mm . Lfl [-l mD mD tH H CN (Y (Y 'T 'T mf Q0 Q0 I- I- m mm H H H H H H H H H H H H H H H

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J-j J-j J-j J-j co co J-j J-j m J-j co m co u u u co J-j co u M J-j u M -1-i m u m co m co J-j co u co m u J-j m co u co J-j co J-j m u m co J-j u J-j J-j J-j m J-j J-j m m u m m m m J-j co J-j u J-j m J-j u u J-j u J-j J-j m J-j J-j u m co co m co u J-j co co co J-j u u co m J-j co u m u J-j J-j J-j J-j J-j u J-j J-j co co J-j u J-j u m u u J-j m J-j m J-j co co J-j u J-j m m J-j u m u J-j m m J-j m J-j J-j co m J-j co 4-jumi-imummi-juUmu umumjjmmmmuujjmmjj J-j m m J-j u u m u m m m m J-j u co co co co J-j co co m J-j m J-j u co mumi-jummmmmmmm J-j m m u m u J-j u m m u J-j u J-j J-j J-j J-j J-j co J-j co u m u J-j J-j co u co u m J-j u co J-j co co co m co J-j u m u u J-j m J-j 4-1 4-1 4-1 4-1 J-j u u J-j m m u m m u m m m u u J-j J-j co m J-j m u co m u m m J-j co J-j J-j J-j co J-j J-j co J-j u u co co u J-j co co co co m J-j J-j J-j co m J-j co J-j co J-j m co co J-j u co u co J-j m J-j co m co J-j J-j u u co co J-j m u u u J-j u co co m u u J-j u u J-j m m u m -1-i m m J-j m co J-j J-j u J-j u m J-j m J-j J-j m u u m u m m m J-j J-j m co co m u co J-j J-j co u co m J-j J-j m co 4-1 u 4-1 co co J-j J-j u m J-j u co J-j m m u u J-j J-j m u m m J-j J-j m u u co u m m m m m u m u u J-j m co co J-j m J-j J-j J-j co co m u co m J-j J-j co coucocoui-icomi-jumi-ico u-l-jmuujjuuummmmmm J-j u m u u J-j u u m m u J-j u u u u J-j u J-j J-j m m J-j u J-j co J-j u u m m m m J-j J-j u J-j m u u u M J-j J-j co co m J-j J-j J-j m J-j co co u J-j J-j J-j co co co m co m co m J-j m u co J-j J-j u J-j co J-j J-j u co J-j m co J-j u co J-j co co u u u J-j J-j J-j J-j m u J-j J-j m u m co u u J-j J-j co co J-j J-j J-j J-j m u co J-j u J-j u m m J-j u m m u u co J-j u m J-j u co co co J-j J-j co J-j co J-j m J-j m co J-j co m u J-j J-j J-j J-j -1-i -1-i -1-i J-j u co m J-j J-j co u J-j J-j m co J-j co co J-j co u u u m J-j u u J-j J-j J-j J-j J-j u J-j J-j J-j co u m co 4-1 4-1 u co m m co u co u J-j J-j m J-j J-j u J-j u J-j m -1-i -1-i J-j co 4-1 4-1 co co J-j J-j J-j J-j u co J-j J-j u co J-j J-j u J-j 4-1 co 4-1 -1-1 u J-j J-j u m J-j J-j J-j J-j J-j J-j m u m u u u m J-j J-j u m m J-j u J-j J-j J-j u J-j m J-j m J-j u m J-j M m m m m u m u J-j J-j u m J-j co u J-j J-j u m m co J-j m co J-j 4.j u 4.j J-j J-j u u J-j m m u J-j u u m m co -1-i m J-j u u m co co u J-j u co co u co u u u u J-j u J-j u co u u J-j -1-i -1-i u m J-j J-j J-j m m u m u u u co co co J-j J-j u u J-j u co m J-j u u J-j J-j J-j co J-j J-j m co J-j J-j u J-j u J-j co u M m J-j J-j m m m J-j J-j J-j J-j J-j J-j u co m co J-j u m co u u m co J-j J-j J-j m m co u co u m m co co co J-j co -1-i u u J-j J-j J-j J-j u co J-j co J-j J-j J-j co u J-j u m J-j J-j co J-j co J-j u u J-j co u J-j m u u co co u J-j co u u J-j u u J-j m m m m M u J-j J-j J-j J-j co u co co u co J-j m u J-j co J-j co u M u u u u u co J-j J-j u u co J-j u m m m u u J-j J-j J-j u u u J-j J-j J-j J-j co co co J-j m u u J-j m m m u J-j m J-j m u m u J-j J-j J-j J-j u J-j J-j J-j u u u u J-j J-j co u J-j J-j m J-j J-j co J-j co co u m J-j J-j m co co J-j m J-j J-j co J-j u u m J-j m u u u m J-j m J-j co co J-j J-j co m m J-j m u m J-j J-j u co co J-j m co J-j u u J-j co co m co J-j m J-j u m m u J-j J-j J-j m J-j m m J-j u u m co m u co co J-j co co J-j m J-j J-j m -1-i co J-j u J-j J-j J-j co co J-j co J-j m mco 4-jummi-jummmummi-i 4-imui-imumui-immmuum u M J-j J-j J-j u J-j u J-j m m u m m J-j m u m u m J-j co u m co m m m J-j co cou umi-jummumuUmmi-i uumjj(ojju(o(ojj(oMj-J(O(O J-j co co m co co J-j u m u co J-j J-j u co m u u m J-j u u m u co J-j u co J-j J-j m u J-j J-j u m m m J-j J-j J-j J-j m J-j co u co J-j u co m co co co J-j J-j co J-j (04-1 ujjmujjmum(ouujju uuUmmumummumi-immm m u J-j u m co m J-j m m co u co u J-j co u u m u u u J-j u m J-j J-j u u J-j J-j J-j m u J-j u J-j u m J-j m u co m co co u u J-j m m u J-j J-j m m m J-j J-j J-j J-j J-j J-j J-j co u J-j J-j m m J-j co J-j m co J-j u u J-j co u co -1-i co -1-i -1-i u co J-j co u u J-j m J-j m mu ui-imcoucoucocomi-jui-ju umumuuuuiiiiuiiuuui-i J-j J-j u m m u m u u co m m co co J-j J-j m co u co m co m m J-j co u co co J-j u co u co J-j J-j J-j m J-j m co co J-j J-j u co u J-j m u J-j co co co m co m J-j co co co J-j co co J-j m J-j m u co u co u co m co J-j co J-j u J-j co J-j co u u J-j u u J-j u J-j M J-j u M co J-j m u u u u u m m J-j m m J-j u J-j J-j J-j co co J-j co J-j J-j m u m co co u J-j J-j u u J-j m co J-j u co J-j u u co u J-j J-j u u co J-j co co co u J-j J-j m J-j co u m J-j J-j Mi-i uuujjummumummjjjj mmuiiuiiuiiuuiiuuiiuu co m m u u u m m u m J-j J-j m J-j u -1-i co -1-i -1-i co co 4-1 4-1 u J-j co J-j m u u m J-j u u m m J-j m m u J-j J-j u u u u u m m m u m J-j J-j J-j m m J-j m J-j m co J-j co co u u u co J-j J-j m co co J-j m J-j m u J-j u u u m m J-j u m J-j u u co J-j m m u u m u u J-j co co m u m u u -1-i u m -1-i J-j u m u u m J-j J-j m uu mmi-immi-jumi-jumui-ii-i umm-l-jm-l-jmmujjuummmm Mi-i mcocoucoummmui-icoi-im Jjmmujjmmjjuuummmuu co J-j u m m u u m m m J-j u u m J-j m co J-j J-j J-j m u m J-j J-j co m co co m m J-j m m u m J-j m u J-j J-j m m J-j m -1-i co u -1-i -1-i co m co co u m J-j m m u u 4-1 u 4-1 m J-j u J-j co J-j J-j u u J-j co J-j co J-j J-j co u

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37324PCT_CRF_sequencelisting 19 Apr 2022

SEQUENCE LISTING

<110> BOLT THREADS, INC. <120> MODIFIED STRAINS FOR THE PRODUCTION OF RECOMBINANT SILK

<130> 27576‐37324/PCT

<140> PCT/US2017/054997 2022202534

<141> 2017‐10‐03

<160> 522

<170> PatentIn version 3.5

<210> 1 <211> 1800 <212> DNA <213> Pichia pastoris

<400> 1 atgttgaagg atcagttctt gttatgggtt gctttgatag cgagcgtacc ggtttccggc 60

gtgatggcag ctcctagcga gtccgggcat aacacggttg aaaaacgaga tgccaaaaac 120

gttgttggcg ttcaacagtt ggacttcagc gttctgaggg gtgattcctt cgaaagtgcc 180

tcttcagaga acgtgcctcg gcttgtgagg agagatgaca cgctagaagc tgagctaatc 240

aaccagcaat cattctactt gtcacgactg aaagttggat cacatcaagc ggatattgga 300

atcctagtgg acacaggatc ctctgattta tgggtaatgg actcggtaaa cccatactgc 360

agtagccgtt cccgcgtgaa gagagatata cacgatgaga agatcgccga atgggatccc 420

atcaatctca agaaaaatga aacttctcag aataaaaatt tttgggattg gctcgttgga 480

actagcacta gttctccttc caccgccacg gcaactggta gtggtagtgg tagtggtagt 540

ggtagtggta gtggtagtgc tgccacagcc gtatcggtaa gttctgcaca ggcaacattg 600

gattgctcta cgtatggaac gtttgatcac gctgattcct cgacgttcca tgacaataat 660

acagactttt tcatctcata cgctgatacc acttttgctt caggaatctg gggttatgac 720

gacgtcatta tcgacggcat agaggtgaaa gaactttcct tcgccgttgc agacatgacc 780

aattcctcta ttggtgtgtt aggtattgga ctgaaaggcc tagaatccac atatgctagt 840

gcatcttcgg tcagtgaaat gtatcagtat gacaatttgc cagccaagat ggtcaccgat 900

gggttgatca acaaaaatgc atactccttg tacttgaact ccaaggacgc ctcaagtggt 960 Page 1

37324PCT_CRF_sequencelisting 19 Apr 2022

tccatcctct ttggaggtgt ggatcatgaa aaatattcgg gacaattgtt gacagttcca 1020

gtcatcaaca cactcgcttc cagtggttac agagaggcaa ttcgtttaca aattacttta 1080

aatggaatag atgtgaaaaa gggttctgac cagggaactc ttttacaagg gagatttgct 1140

gcattattgg actctggagc tacgctaacg tatgctcctt cttctgtttt aaattcaatt 1200 2022202534

ggccggaacc tgggcggctc ctatgattcg tcaagacaag cttataccat tcgttgtgtt 1260

tctgcatcag ataccacttc tctggtattc aattttgggg gtgctacagt ggaagtttcc 1320

ctgtacgatc tacagattgc aacatattac accgggggaa gtgccacgca atgtcttatt 1380

ggaatattca gctctggaag tgatgagttt gtgctcggtg ataccttctt gaggtcagcc 1440

tacgtggttt acgatcttga tgggcttgaa gtgtcgcttg cccaagccaa cttcaacgaa 1500

accgattctg atgttgaggc tattacctcc agtgtacctt ccgctactcg tgcatccgga 1560

tacagttcta catggtctgg ttctgccagc ggtacagttt acacttcggt tcagatggaa 1620

tccggtgctg cttccagctc caactcttct ggatcgaata tgggttcctc ttcctcatcg 1680

tcctcttcat cgtcctcgac ttccagtgga gacgaagaag gagggagctc cgccaacagg 1740

gtccccttca gctacctttc tctctgtttg gtagttattc tcggcgtgtg tatagtatag 1800

<210> 2 <211> 1781 <212> DNA <213> Pichia pastoris

<400> 2 atgatcatca accacttggt attgacagcc ctcagcattg cactagcaag tgcgcaactc 60

caatcgcctt tcaaggctaa caagttgcca ttcaaaaagt ttatcattcc aacgacccaa 120

aggaccgttt aattaagaga gatgactacg agtccctcga cttgagacac atcggagtct 180

tgtacactgc agagatccaa attggatctg acgaaactga aattgaggtc attgtcgaca 240

ctggttctgc cgacttgtgg gtcatcgatt ccgacgctgc cgtctgtgag ttatcctacg 300

atgagattga ggccaatagc ttttcctcgg cttctgccaa attcatggac aagatagctc 360

ctccatcaca agagctcctg gatgggctga gtgagtttgg atttgctctc gatggtgaaa 420

tttctcaata cctagccgat aaatctggac gtgtttcgaa aagagaggaa aatcaacaag 480

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37324PCT_CRF_sequencelisting 19 Apr 2022

atttcaacat taaccgtgac gagcctgtgt gtgaacagtt tggttccttc gattctagtt 540

cttccgacac tttccaaagc aacaattcag cttttggtat tgcttacctt gatggaacca 600

ctgctaacgg aacttgggtc agggacacag tccgcatcgg cgactttgcc atcagccaac 660

agagttttgc cttagtcaac atcacagata actacatggg aatcttgggt ctcggtcctg 720

ctacccaaca aaccaccaat agtaacccaa ttgcagcaaa cagatttact tatgatggtg 780 2022202534

ttgtggattc attgcggtcc caaggattta tcaattcagc atcgttttct gtttacttgt 840

ctccagatga agataacgag cacgacgaat tcagcgacgg agaaatttta tttggtgcta 900

ttgatagggc caagatagac gggccattta gacttttccc atatgtcaat ccttacaaac 960

cagtttaccc cgatcaatat acttcctacg ttacagtgtc cacaattgcg gtgtcttcgt 1020

cagatgaaac tctcattatt gaaagacgtc ctcgtttggc attaatcgat acaggtgcca 1080

ccttctccta tttgccaacc tacccattga ttcgtttagc gttttccatc catggaggct 1140

ttgaatatgt ttctcaattg ggactatttg tcattcgtac aagttctctg tctgttgcta 1200

gaaataaggt gattgagttc aagtttggtg aagacgttgt gatccaatcc ccagtttctg 1260

atcatctatt ggacgtctca ggccttttta ctgatggcca acaatactcc gcattaactg 1320

tacgtgaaag tcttgacgga ctttccattc taggtgatac attcatcaaa tcggcctact 1380

tattctttga caatgaaaac agccagctgg gtattggtca gatcaacgtc actgatgacg 1440

aggatattga ggtggtcggt gatttcacta ttgaacgaga cccagcctac tcctctactt 1500

ggtctagcga tttacctcat gaaacaccca ctagggcttt gagtactgct tcagggggag 1560

gccttggtac cggaataaac acggccacaa gtcgtgcaag ttctcgttcc acatctggct 1620

ctacttcacg aacttcttct acatctggct ctgcttctgg tacttcttca ggtgcatctt 1680

ctgctactca aaatgacgaa acatccactg atcttggagc tccagctgca tctttaagtg 1740

caacgccatg tctttttgcc atcttgctgc tcatgttgta g 1781

<210> 3 <211> 1584 <212> DNA <213> Pichia pastoris

<400> 3 atgaacccta gcagcttaat tctacttgca ctcagcattg gctactccat tgctgagtca 60 Page 3

37324PCT_CRF_sequencelisting 19 Apr 2022

aatttctctt tcaaacccag caagttacct ctcaaaaaac atcgtgattc ttcttccccg 120

catgaacgat ttcttaaacg agatggaccc tatcatccgc tagaagccga cgcttacttt 180

tactacacta cgtctatatt ggttggatca gaagaagaaa aagttgaagt aacagttgat 240

ttaggaacct ctgatttatg ggtcgtcgat tacaacaccg gtttatgtga tagatccttt 300 2022202534

gacgaaacct atcttaaacg tagtctggat acttctgagg aagattattc tgctggagat 360

cttggctcct cagtcggtgt acgcagcgct agaaaattct tgcgcaaaag ggacaccaat 420

caaactgagg ttaatgaagc taactatggt gcttgtccaa attcgattac cttcaatcca 480

gaaaactcgt cttctttcca gagtaatgat actgctttca atatcagcta ctttgatgga 540

accagtgcta gtggtttttg ggctactgat acaatttact ttggtgacct tgaggtcagc 600

gagcaatttt ttgggctggc aaacttaaca ataagttatg gaggagtctt aggtcttggc 660

ccttccaacc tacaaacaac caatgctaac cccaacggtg aggaattcat ttacagcgga 720

gtcttagatt ccatgcgtga tcaagggctt atcaactcgg cttctttctc aatctatctc 780

aatccagaga atttcagaga tgaagataac tattctaatg aaggagcgat tttgttcgga 840

gcaattgata atgcgaagat tgacgggtca ttgaagctgt taccatacgt gacttcaggt 900

ggacactctc agattgatgc taatttcact tacatcacct tgaataatat tgccgtggct 960

gacaatgata cagccctgat cgttgagacc aacccccaat tggcaatgtt gaatccaaag 1020

tttatataca cctattttcc aaacgaagta ttgacccggc tggtaaactc tattgacaat 1080

ctagaatatg atcctgttga ggggttatat aggataagga gaacaaacat tagggatatt 1140

aacaaaaaaa tcatagagtt tcaatttggt gacgagattg tgatacattc tcccttatca 1200

aattatctgt ctgatacatg ggttccaagc acaaactaca cctatttgga gattcaggat 1260

agcagagagg atttctttat ccttggtaat gcatttttca agtctgcgta tttgtttttt 1320

gacaatgata acagtgaagt cggtattggc caactaaagg ttaccgataa ggaggacatc 1380

gttccagttg gtgaattttc tttggatcaa gattcagggt actcgtcaac ctggtcaacg 1440

ttctcctatg aaactggttc agctcccttg ggtacgtcaa ctttcgaaac gagtacaaaa 1500

actagttcag atggagctgc cccgtcggtg tctcacatta acactagttc ctacttattt 1560

gcgtttgtac tacttttcct ttag 1584 Page 4

37324PCT_CRF_sequencelisting 19 Apr 2022

<210> 4 <211> 1422 <212> DNA <213> Pichia pastoris

<400> 4 atgttgccca tccgcttatc caaacttctg cttttgctct ccttaaagtt gaaattgggt 60 2022202534

acagctgaag aaaaatacca aaagttggat ttaaaaagaa ttgacaaaga ctattatgcc 120

gtcgatgtca aagtcggctc cgatgagcag gagatcaaag aggtactaat agatacgggt 180

tcatctgatt tctggatctt ggacaaatcg ttctgtaatt ctccaacatc agaggaagaa 240

gagaacagta acgggcgtag caacaaggaa agctgtggag tctatggctc gttcgactcc 300

aacaagtcag agacatttca ggcaactggc caagtatttg acgctgctta cggtgacacc 360

acagccgagt cgacaggatc ttcaggagtt cgaggaattg atcagctacg ggtaggagat 420

attcatatag aagaactcta ttttggacta gtgacaaaca ctacaagttt accacccgtt 480

ttaggaattg cccagctttc cgaagagttc agcaacaact cttatcctaa ctttccatac 540

cagatgaaag aggaaggtct gattgatgtt gttgcatact ctctctcctt gggccaaagt 600

aaaggtgaac tactgttcgg ggctatggac cactcaaaat ataatggaac actattgaaa 660

gcccctatat tgcaggcggg cacaccagga atgcaagttc ttttaactgg agtggccctt 720

acaaatggtt catcaagcgt cttcaatgag acagacaata aaggttttat ctactttgac 780

agtgggacta ctgcttccac tctgccatca gagcactttg atgatctttt caaccatcac 840

ggatgggcgt acgatggtga tacattgaca tattcgattc aatgcgatag tgagggagaa 900

aaatctttac ttgacttcac tttagaatat accattgctg gtaatattgt catcaaagta 960

ccatttgaag acattattat gaagaatgaa aatgatggag aatgcctctc aaccgtaatg 1020

gtgtcgaacc agacttcttt ttcatattcc gatgacacac cctttttcgt tgctggagac 1080

gaagttctgt tgaacgctta tgttgtttac aacctagaaa cacaagagct ggccattgct 1140

ccagcagtgg ataatccaga agatactgaa gaagatattg agattatctc cgcagacttt 1200

gatatttcag aagccagaga ttatagcgtt ggattagagt tcagaaatac cacaattcca 1260

gctacaactg attacttgcc ttcctcgatg tcgtcaggtt cagtcagcga agagactggt 1320

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37324PCT_CRF_sequencelisting 19 Apr 2022

tccaagtctg agagctctac ttctgaggac tttgctgcag ccacgttgaa accatttaca 1380

ttttggggtt tcgtcctttt tttctttcac tttttgattt ga 1422

<210> 5 <211> 1839 <212> DNA <213> Pichia pastoris 2022202534

<400> 5 atgttagttg ctgttgccct agtgttgtta ctgtctacag gctatgctgg aatcgtcgcc 60

attgataccg aatatgagtt caccattggt tttcttagta cgatagaaat agggtttccc 120

ccacaaagca taacggctca atgggataca ggatcgtctg acctcttggt caattccgtg 180

acaaattcac agtgtgctca ggacggatgt agctttggtg cgttcgcctt caacaaatcc 240

accacttatt ccaatataac aaaccctaac aaccttcatg ttcagttctc ctttgcaagc 300

ggcagcgtgg ttgatgacaa acttgtgagt gacactattt ttgtagattc caaggtaatc 360

ccacggttca actttgcact ggtatcgaag ggagacctgt atggtgataa tatttttggt 420

attggaccga gagggaacca gggaacattc gattccaatg gaactccagc tttctatgat 480

agctttcctt atcacttgaa ggccctcggt ttaatcaaac gactggctta ctcattttac 540

actgggccca cccagggaaa ggtagtattt ggaggggtgg atcatggaaa gtacgatggg 600

tgcctggaga aactcgagat tgtccatgac agtgcttttt acacactgct tgaggcaatt 660

gatgctgatg atacttccgt cttggatgag caaattcatg ttttgtttga tactggtacc 720

gccttgacac tttttcccag ctttattgct gaacaactgg ctgatttttt gaaagctaca 780

tattcggacg aatacaatac gtttgtagtt ccctgcgacc aagattttga ttttgaatac 840

cttcattttg gttttcgaaa cattaagttg tcggtgcgct ttaaggatct gtttttagtc 900

attgacgata gtgtttgtgc tgtggggttt gatcaagggg cagatgcaaa caagataacc 960

tttgggtctt cacttttaag aaactactac acgctttatg atctagattc caaagaaatt 1020

ttgattgctg acgtcaagcc tgatggtcca gacgatattg aaatattatc gggtccagtt 1080

caacgaattt gtgatgaaaa gggtgtcagt agcacttcat tatggagtag tctgagtata 1140

gagtccacga tagaaccaga cacttttacc actaagcctt ctatttccca gacacggtat 1200

tcgactagct ccattggacc tcaaaacatt tctaactctt taggtgaata tccttcagtt 1260 Page 6

37324PCT_CRF_sequencelisting 19 Apr 2022

tccgtcactc tttctgaaca ccataacact acttccatag cctcaaattc ctcattagaa 1320

gggaaaccag caactccaac tgttacagac cagtcgtacc agaataataa gactacctct 1380

accgtaattg ctgtgaattt gattacccat tcaaccactc attcaaccac tcattcaccc 1440

acctattcaa ccactcattc tagtaatgga tcacgctcaa ctttagagta cacttcaacc 1500 2022202534

aaggaatcct cggtgaaaat gccctgtgcg ttgatcatct ccgacacaat tccgtacaat 1560

gcttccggtg ggaatagtag ttatggatcg ttaatttcaa catctacggt taacaatgtt 1620

gaagagaata attcaaacac tgttagacca agaaaaagac agaccttcgt ttcgggaacc 1680

acttccacga tactactcta ttcctcaact acgacccaag catatcagat gttgtcctca 1740

acttcaatcc cccgaccatc cataaaagcc agttcaaatg ctggtagccg caaaacttca 1800

aagacattat taacatttat catattgtat attttttag 1839

<210> 6 <211> 1749 <212> DNA <213> Pichia pastoris

<400> 6 atgtaccagg cgttgttggt tttgtctctg atatgctttt cgtcggctaa ttttgttaag 60

ctgcgaagca acgctggtat gttttatgat actatggctg gagttccacg ttcagatgaa 120

gagttctggt tgcgtttgga tattaaccaa ggtctctctt ggactctgga tagtagctac 180

tactcctgta atggctcaaa tgtttcgtct tccctgtgtt tcaattctgc tcaaaacgtt 240

tacgatgctt ccaatagtcc aactgcagat ttcgttgatg tctacgcaaa cacaactgta 300

aacaatacag atgaggcatc ggccgagaga gtaaatctta caaacaactt atttgctgat 360

ggcgtttata tggaagacaa tttttacgtc acattgaata atggagcaag aatgactgct 420

acagatctga aatttttgaa tgcccacaat agtagcgccg ctgtggggtc tttggcgttg 480

gggagttaca cctcacagga cgtgccaact ttcttacaaa gactccaaag cggtggtctt 540

attgaatcca actcgttttc attggcatta aacgaaatcg attcttcata tggagagctc 600

tatttgggga caataaactc taccaagtat gtcgagcctc tggtagaatt cgattttatt 660

ccggtgtcag atcccaatgg agtttttgga ttcgattggg aagatacatt ccctacagtt 720

Page 7

37324PCT_CRF_sequencelisting 19 Apr 2022

ccgatcagcg gattaagcat gtcttcgaat gacaaacaga gaactgtctt tttccccaat 780

gagtggaaca acacggtctt aacgggaaca tacccacttc caatgatgtt agattcaaga 840

aacatcttta tccatcttcc attctcttca atcatacata tagcagtgca gcttaatgca 900

ctgtatcttg atacacttca taaatgggcc gtgaactgtt ctgttggtca actggacgca 960

actttaaact ttcacatggg taaccttacc gttcatgctc ctatcaagga gttgatttat 1020 2022202534

ccagcatacc aaggagacaa aaggctgagc tttgctaatg gagaagatgt ttgtattctt 1080

gccatggctc ctgatgttta cattggttat ccactgctag gaaccccctt tttaaggaat 1140

gcagtggttg ccgttaatca tgattcaaaa aaggtcgccg ttgccaatct taatagagat 1200

agcattcctc ccgcttcgaa cgtttctgtt tcggaatcaa tgggagttta tgttcctcca 1260

cctgtttcaa cttcaagaac atcggagaga ccgtccacac tagatgagac tagtacagcc 1320

aattttgaca aaagggaaga gtctgcaata tcatcaagtt cagtcactaa cagctcgtct 1380

agaaattctt caaccataac ttcttcagga actcaaaccg agcaaacatc aggcatagct 1440

accatcgaaa cagatagcat accaggagct ctagggaata atttaactga ttattcaacg 1500

ctgactctaa caatatacac caattccgaa gtggacgaac tcaatcctaa catagcaaca 1560

gcattcattt ccaatggttc tatttattca gagccttacc ccttttccgg aactgcagtt 1620

gctgaatcat tcagtgcatc accttcacag gctgaaggat cgaactcatc gtcctcagga 1680

tcttctttag ttttgtgttt ctttacatca ttggccagtc tgttgactgt gagctgtcta 1740

ctactgtaa 1749

<210> 7 <211> 1895 <212> DNA <213> Pichia pastoris

<400> 7 atgtttgtga tccagctggc attcctatgt ctaggcgtca gcctaaccac tgcacaacct 60

agttcacctt tcaaggcaaa taagtttcct tttaaaaagg ttcactactc atcaaaccct 120

agcgatcgcc ttattaagcg agacaactat aagaagcttg acttgagaca tcttggcgtc 180

ttgtatactg cggaaattga aattggttca ggcaaaactg aaatcgaagt tattgttgac 240

accggatctg cagatttgtg ggtaattgac tcaaatgcag ccgtatgcga ttgtcctatc 300 Page 8

37324PCT_CRF_sequencelisting 19 Apr 2022

ttgagataca aggtacaagt gtttccaccc ttagtcaaac tgccaacgta acacccctat 360

caggtaaact tttgaatgga cttcaagaaa ttggcattgt aactgatggc aaaatttcca 420

aaaagtttca ggaaaaccat cttttgaaga gaaacgaggc cttgaatttt gatgtcgatc 480

tgaataagcc catttgtgat caatttggat ccttcaatcc acagtcatca agaacttttc 540 2022202534

aaagcaacga cacagcattt agtatcagat atctggacaa ctcttttgcc aatggatcgt 600

gggtgaggga tacggtttat gttggtgatt ttgaaattga ccagcaaagt tttgcattgg 660

ttgatatcac aaataactac atgggaattc tgggccttgg tccttctagt cagcagacaa 720

ccaatagtga tcctacagat aacagtttca cttatcttgg tattctggat tctttgcggg 780

cccaaggatt cattaattca gcctcgtact cggtttatct ggccccagat ggtaagactg 840

atgatactga tcacgatgat ggtgagatcc tgtttggtgc tatcgacgag gctaaaatta 900

atggacagtt gaagttgttt ccatatgtca atccttataa atcggtatac cctgaccaat 960

acgcttcata catcaccgtt tccagtatta ctgtagccag ttattttagt agccgcttgg 1020

ttgaaagaat ccctcaatta gctcttttag acactggtgc cacattttct tacttgccaa 1080

cttatacgct gatacgtctc gcctatgcca tccatcctgg ttttgagtat gtccgacaac 1140

tgggtttatt tattatagag tcaaacgtac tctccagtgc gagacaaagt accattgact 1200

tccggtttgg caaagacgta gtaattcgat ccaatgtttc agaccatcta ctcgacgtat 1260

cacaatactt cacatctgga cattatcttg cacttaccat ccatgaaagt gtcgatgggc 1320

ttctcatttt gggtgacacg tttatcaagt ccacctactt atttttcgac aatgataaca 1380

gtgaattggg tattggtcag atcaaaatta ccaatgacga ggatattcaa gaagttggtg 1440

aattcacctt agaacgcgat tcagactatt cttctacatg gtccatttac tcttatgaaa 1500

cttctttgga tcccttaagc actggcactg gtacggggtc aacctattct cctactcgca 1560

gtactacagc tagaagcgaa ccgactacgt ctcgacgctc caccaccctt caacccagaa 1620

caactgtgat tccttctatt gacaggcttt cattgaacag cataactagt catggttcct 1680

ctactaacgg aacctcccca actaatgaga cttcttttgc tgaggatgga ggaactttga 1740

cacccgaaga agcttctttg acaacttcac taaattctgc tactatttct gagactactt 1800

ttgtcgatgt tgaaacttct actaccaatg gtgcttcagt tgtatctttg agtgttggtc 1860 Page 9

37324PCT_CRF_sequencelisting 19 Apr 2022

cctgcattat tgccttccta ctactcatct cttaa 1895

<210> 8 <211> 3201 <212> DNA <213> Pichia pastoris 2022202534

<400> 8 atgagcatgg gagctactgt ttcaaaggag tccactgtag acctaacact gccgctgttg 60

cagctgagtc caagactgtt gttcctgcct ggagttgtct acaagacgac tttcaagttc 120

caggaggggg tcaacatctt gctacgtttt agagacctgt tcgatgagtc tttttctgaa 180

agaaatgacg ttctaggtga tattgcccgc tcgcagaagg aacaacagga aaacgattat 240

gaccatatcc cttttttgag cagcaatgct aagaagagca taggtgtcct gaaagaccaa 300

cttgaacttg gtgggtctga tgacaagtca cttccctggg ttattgcctg tctccctggg 360

ttcgaccagt cagaccagga ctccattgcc actacaattt gtcagataac tgaggtgtcc 420

gtcgttaacc aggatattgt actatccttc gaagcattaa ccagaggatc tttaaaatcc 480

aaaaagacca tctccatgaa tgaatcaacc atatctgtgg aagtggatat accatttact 540

gaggttgacc agaccatcag taacaagctc atcttgacaa atattgataa gggtctgcaa 600

ctactggaga atatcaaaca gtttctagtc acctatcaaa atgacatgat gaaccttgaa 660

gatactacca tggaaaagaa ctcccgtcta aagtctgcaa tgatgatttt ggctccgttg 720

tctcacttga tctacgccac tgtctcatct caagaatcca ctcatgctta tactagacta 780

tccaaccagt acaagtccgc taagaaggaa ttagattcaa ccaaaaacag aaagtcttta 840

ctcaagaaga ttttgaaaac taatgatatt ctcacttcag tgttcccctt cagtatggtt 900

caaaaggtgg atgtcttggg agctatttca agttctacag acaggatcca aacaactatc 960

gacgcgttgg actttgccaa tccacttttc gaaacatatt tgaacgttga ttatgttctg 1020

gagacatgga aagattttga cactaagaac ggcaaaattg ctgccaattt gaccaggtct 1080

caattagtat ctaaccactt gaagggcctc agagtactga ttgaagacat ccaaggaact 1140

tcaagaaggc gggtcagtcc ttctcagaga actcgtttgg cgccttcgcc caatacaaat 1200

tctgcaaatc aggcaccgaa agctggagaa tcagacgacg aaaataaaga attgcgtgat 1260

Page 10

37324PCT_CRF_sequencelisting 19 Apr 2022

tttatcaaca acctctccaa attgaagatc tcagaggatg gaaagaggct cgttaccaaa 1320

gatttcaaca gaatgactca aatgcaacca agttcatcgg agtaccaact gctcagaact 1380

tatttagaga ttattatgga tatcccatgg gaaacaaaaa atattgtaaa acaacaaatt 1440

tttgatctag acaaggccaa agaaacacta gatcaggacc attacggaat ggactccgtc 1500

aaagatagga tcttagagta tttagcagtt cttaaactcc acgatcacat taaaacgtcc 1560 2022202534

aaccccaagc aagaagacga ggaaatcaaa gccagagcac ccattctctt actaacaggt 1620

ccacctggtg ttggtaaaac ttcgttagga aaatctattg caaaggctct gaacaaaaag 1680

ttccagcgag taagtcttgg aggattgaag gatgagtccg aaattaaggg acatcgcaga 1740

acttacgttg gagcaatgcc aggactattg acccaagcac tgaggaaatc tcaatctttt 1800

gatccagtga tacttttgga tgaaattgac aaggttgtcg atggatccca aggccctggt 1860

agtcgtgtaa acggtgatcc agctgctgct ttgcttgaag tgttagaccc agagcaaaat 1920

tctaacttct ctgaccatta tatcgggttc ccacttgact tgtctcgtgt tgtttttatc 1980

tgtacgtcca acgatatgag catgatcagt gccccattaa gggatagaat ggaggttatt 2040

gaactgaatg gctacaatta tttcgaaaaa gtggagattg ttaaacaatt cttattacca 2100

aagcagatca aaagaaacgg actgcctacg aatgccgaat caccatcggt ggttattcct 2160

gacgaagtga ttatgtacat cgctgtcaat tatactcggg agccaggtat tcgtaatttg 2220

gaacggttaa tagggagtat ctgtcggggt aaggctattg aatactctag cttgatgagt 2280

agtactcaag ctccaggcga aattccaaag ggatacgttt ccaaggtcac ggtagataat 2340

ctttcaaagt acattggaat acccccggaa ttgtctacag gcaagaatat gaggaatgat 2400

tcagctatct ctaaaaagta cggaatcgtg aacggcctca gttacaatag tagcggacat 2460

ggaagtaccc tagtctttga aatgaccggt atacctaata gtactaacac taacatgatt 2520

acgaccggca gattgggtga tgttcttaca gaaagtgtca agatcgcaag aacaattata 2580

agatcgatgt ttagtcacaa cttactacaa ttaaaggatg acgaaacttc aacttctggg 2640

gatcttttga agaggtttga cactactcag gttcacatgc atgtgcccgc tggtgctatt 2700

caaaaagacg gacccagtgc tggaatcacc attacgctgt gccttctgtc ggtgatgcta 2760

gagaaacctg taccaaggga tttggccatg actggagaga ttactttgag agggatggta 2820

Page 11

37324PCT_CRF_sequencelisting 19 Apr 2022

ctgccaattg gaggtgttca tgagaagcta ctaggagcac atttaactgg aaccgttaaa 2880

agggtgatcc ttccaagaag taatcgaaga gatgtcattc aagactttat ctctaacttg 2940

gaagccaata acagaagttc tagggataag ctactggtag atcttatcaa agaggaggag 3000

tcattactgt ccaactcaaa taaatccgaa cgaattggag tgttcgggct tcctgaaaaa 3060

tgggttcaag agaagttggg acttcaagtg agctacgtgg aagaattttg ggatgttatc 3120 2022202534

cagattgtct ggaacgatca ggttgaaatt gacagcacca aattacacga gctagctact 3180

aaagagttcg caaggctatg a 3201

<210> 9 <211> 1680 <212> DNA <213> Pichia pastoris

<400> 9 atgcaattgc gtcattccgt tggattggct atcttatctg ccatagcagt ccaaggattg 60

ctaattccta acattgagtc attacccagc cagtttggtg ctaatggtga cagtgaacaa 120

ggtgtattag cccaccatgg taaacatcct aaagttgata tggctcacca tggaaagcat 180

cctaaaatcg ctaaggattc caagggacac cctaagcttt gccctgaagc tttgaagaag 240

atgaaagaag gccacccttc ggctccagtc attactaccc attccgcttc taaaaactta 300

atcccttact cttatattat agtcttcaag aagggtgtca cttcagagga tatcgacttc 360

caccgtgacc ttatctccac tcttcatgaa gagtctgtga gcaaattaag agagtcagat 420

ccaaatcact catttttcgt ttctaatgag aatggcgaaa caggttacac cggtgacttc 480

tccgttggtg acttgctcaa gggttacacc ggatacttca cggatgacac tttagagctt 540

atcagtaagc atccagcagt tgctttcatt gaaagggatt cgagagtatt tgccaccgat 600

tttgaaactc aaaacggtgc tccttggggt ttggccagag tctctcacag aaagcctctt 660

tccctaggca gcttcaacaa gtacttatat gatggagctg gtggtgaagg tgttacttcc 720

tatgttatcg atacaggtat ccacgtcact cacaaagaat tccagggtag agcatcttgg 780

ggtaagacca ttccagctgg agacgttgat gacgatggaa acggtcacgg aactcactgt 840

gctggtacca ttgcttctga aagctacggt gttgccaaga aggctaatgt tgttgccatc 900

aaggtcttga gatctaatgg ttctggttcg atgtcagatg ttctgaaggg tgttgagtat 960 Page 12

37324PCT_CRF_sequencelisting 19 Apr 2022

gccacccaat cccacttgga tgctgttaaa aagggcaaca agaaatttaa gggctctacc 1020

gctaacatgt cactgggtgg tggtaaatct cctgctttgg accttgcagt caatgctgct 1080

gttaagaatg gtattcactt tgccgttgca gcaggtaacg aaaaccaaga tgcttgtaac 1140

acctcgccag cagctgctga gaatgccatc accgtcggtg catcaacctt atcagacgct 1200 2022202534

agagcttact tttctaacta cggtaaatgt gttgacattt tcgctccagg tttaaacatt 1260

ctttctacct acactggttc ggatgacgca actgctacct tgtctggtac ttcaatggcc 1320

tctcctcaca ttgctggtct gttgacttac ttcctatcat tgcagcctgc tgctggatct 1380

ctgtactcta acggaggatc tgagggtgtc acacctgctc aattgaaaaa gaacctcctc 1440

aagtatgcat ctgtcggagt attagaggat gttccagaag acactccaaa cctcttggtt 1500

tacaatggtg gtggacaaaa cctttcttct ttctggggaa aggagacaga agacaatgtt 1560

gcttcctccg acgatactgg tgagtttcac tcttttgtga acaagcttga atcagctgtt 1620

gaaaacttgg cccaagagtt tgcacattca gtgaaggagc tggcttctga acttatttag 1680

<210> 10 <211> 1233 <212> DNA <213> Pichia pastoris

<400> 10 atgatatttg acggtactac gatgtcaatt gccattggtt tgctctctac tctaggtatt 60

ggtgctgaag ccaaagttca ttctgctaag atacacaagc atccagtctc agaaacttta 120

aaagaggcca attttgggca gtatgtctct gctctggaac ataaatatgt ttctctgttc 180

aacgaacaaa atgctttgtc caagtcgaat tttatgtctc agcaagatgg ttttgccgtt 240

gaagcttcgc atgatgctcc acttacaaac tatcttaacg ctcagtattt tactgaggta 300

tcattaggta cccctccaca atcgttcaag gtgattcttg acacaggatc ctccaattta 360

tgggttccta gcaaagattg tggatcatta gcttgcttct tgcatgctaa gtatgaccat 420

gatgagtctt ctacttataa gaagaatggt agtagctttg aaattaggta tggatccggt 480

tccatggaag ggtatgtttc tcaggatgtg ttgcaaattg gggatttgac cattcccaaa 540

gttgattttg ctgaggccac atcggagccg gggttggcct tcgcttttgg caaatttgac 600

Page 13

37324PCT_CRF_sequencelisting 19 Apr 2022

ggaattttgg ggcttgctta tgattcaata tcagtaaata agattgttcc tccaatttac 660

aaggctttgg aattagatct ccttgacgaa ccaaaatttg ccttctactt gggggatacg 720

gacaaagatg aatccgatgg cggtttggcc acatttggtg gtgtggacaa atctaagtat 780

gaaggaaaga tcacctggtt gcctgtcaga agaaaggctt actgggaggt ctcttttgat 840

ggtgtaggtt tgggatccga atatgctgaa ttgcaaaaaa ctggtgcagc catcgacact 900 2022202534

ggaacctcat tgattgcttt gcccagtggc ctagctgaaa ttctcaatgc agaaattggt 960

gctaccaagg gttggtctgg tcaatacgct gtggactgtg acactagaga ctctttgcca 1020

gacttaactt taaccttcgc cggttacaac tttaccatta ctccatatga ctatactttg 1080

gaggtttctg ggtcatgtat tagtgctttc acccccatgg actttcctga accaataggt 1140

cctttggcaa tcattggtga ctcgttcttg agaaaatatt actcagttta tgacctaggc 1200

aaagatgcag taggtttagc caagtctatt tag 1233

<210> 11 <211> 942 <212> DNA <213> Pichia pastoris

<400> 11 atgaagctct ccaccaattt gattctagct attgcagcag cttccgccgt tgtctcagct 60

gctccagttg ctccagccga agaggcagca aaccacttgc acaagcgtgc ttactacacc 120

gacacaacca agactcacac tttcactgag gttgttactg tctaccgaac tttgaaaccg 180

ggcgaaagta tcccaactga ctctccaagc cacggtggta aaagtactaa aaagggtaag 240

ggtagtacca ctcactctgg tgctccagga gctacctctg gtgctccaac tgacgacacc 300

acttcgacta gtggctcagt agggttacca actagcgcaa cttcagttac ctcttctacc 360

tcctctgcaa gtacaacaag cagtggaact tcagccacta gcactggtac cggtactagc 420

actagcacta gcactggtac tggtactggt actacaggca caggaaccac tagttccagc 480

actagctctt ctgctacttc gactccaacc ggttctatcg acgctatcag ccagacactt 540

ctggatactc acaatgataa gcgtgctttg cacggcgtcc cagaccttac ttggtctacc 600

gaactcgctg actacgccca aggttacgcc gattcataca cttgtggctc ttcattagaa 660

cacacaggtg gaccatacgg tgaaaatttg gcctctggat actctcctgc tggcagtgta 720 Page 14

37324PCT_CRF_sequencelisting 19 Apr 2022

gaagcatggt acaacgagat cagcgactac gatttctcta acccaggtta ttctgctggt 780

accggtcact tcacccaagt tgtctggaaa tcaactacac agctgggctg tggatacaag 840

gagtgcagta ccgacagata ctacatcatc tgcgaatacg cacctcgtgg aaatattgtt 900

tctgccggct acttcgaaga caacgtcctg cctcctgttt ga 942 2022202534

<210> 12 <211> 690 <212> DNA <213> Pichia pastoris

<400> 12 atgactgtgc aaattttgat tgtagttacc agtgttgcta agtatgaaag cggaaagctg 60

ccaacaggct tgtggttaag tgagttgaca catatgtatc atagtgcaaa agagaacggc 120

tatgatgtga cgattgcgag tccgcaaggc ggaaacattc cgcttgaccc tgaaagcttg 180

aaatcaatgc tgattgacaa gctttcaaag gattatgaga caaaccaaga ctttatgaag 240

ttgttgcaaa acacaaaaag tttgggtgaa gtcacaggac aacagtttga cgttgtttat 300

ttggcaggtg gacacggaac aatgtatgac tttccgaaca acactgtttt acaaaacatc 360

atcaaagaac actatgaggc gggcaaaatt gttgccgctg tatgtcacgg agtttgtggg 420

cttttgaacg taaaactgtc tgatggcgag tatctaatca aagacaaggc cattacagga 480

tttaattggt ttgaagaagc tatagcagga cgcagaaaag aagtaccgtt caaccttgaa 540

gcagaattga ataaaaaaac ttcaaaatac gagaaagctt ttatcccaat gacgtcaaaa 600

gtggtcgtgg acgggaactt aatcacagga cagaacccat tcagttcaaa agaaattgcg 660

aaagtggtaa tggaacaact gaagcaataa 690

<210> 13 <211> 2517 <212> DNA <213> Pichia pastoris

<400> 13 atgattgatg agaagcaatt gaatcaaccc aaaaggagcg tcttaagacg tctccatatg 60

ctgtttctgc cattactagc tatctccttt ttcctgatat atttaagtga tatcacacag 120

cctctcttcc gtgcccgaaa ggaagacgaa aacccgttgg aaatttactt gaaggcattg 180 Page 15

37324PCT_CRF_sequencelisting 19 Apr 2022

gaaacgaatg aagctcacaa atggtcaaag gtgtacactt cgcagcctca tttggccgga 240

accaactacg gattggttga gtttactaag tccaaatttg aagaatatgg atttgaggcc 300

agtgtcgatg actacgatgt gtacctgagt taccctattg atcatagttt ggaattgtat 360

gagcattctg aggataaaaa tgacaagctc ttgtataagg cttcgctgca agaggacgtt 420 2022202534

ctctctgaag acccaactac ttcaggcgac gacctgatcc ctaccttcct tggttacggt 480

gctaacggca atgtatctgc agaatacatc tacgctaact atggaaccaa agaggacttt 540

gaggatttgg tggcccgtgg tgttccaatc aaggggaaga tcgcagtcat tagatatggt 600

caaatattta gaggcttaaa ggtgaaattt gcccaagaat atggcgcaat cggtgctgtc 660

atatacagtg acccaggcga cgattatggt atcacccctg aaaatggtta caagccttac 720

cctcatggta aagccagaaa cccaagctct gtgcaaagag gttctgccca atttttgtct 780

gtttatcccg gtgacccaac cacgccagga gttggatcga agaagggagt agaaagagtt 840

gatcctcatg ctacaacccc ttccattcca gtcttgcctt tgagtttcaa agatgccttg 900

ccaattttga agaaacttaa taaggaagga ttgtctgttc ctgactcctg gaagggaggt 960

ctcgagggag ttgattacag taccggccca gctaaaaaca ttcatttgaa cctttatagc 1020

gaacaaaact ttactattac acctatttac aatgtctatg gagagatcaa aggtgagaat 1080

gctgacgaag ttatcattat tggtaaccat cgtgacgctt ggattaaggg aggtgcttct 1140

gaccctaaca gtggatctgc tgctttgatt gaacttagta gaggtttgca cgccctaacc 1200

aaaacaggat ggaagccaca ccgtactatt gtactagctt cctgggatgc tgaggaatat 1260

ggcttgattg gatctactga gtttggagaa cagtttgaga agttccttca gaagaaggtc 1320

gttgcctatt tgaacgttga cgttgctgta gctggaactc atcttcattt gggtgcctcg 1380

ccatctttgt tcaaactatt gaaggataat gccaaagaaa tcactttcaa gaattcaacc 1440

gagactttgt atgacaacta tgttaaagat catggcaacg acattatttc gaccttagga 1500

agtggaagtg actacactgt ctttttggat catttgggaa ttccttcgct tgatattggt 1560

ttcattgctg gaaaaggtga cccagtatat cactatcatt caaactatga ttcgtaccac 1620

tggatcagta ctagtggtga tcctggattt gagtatcata atgtactggc caaatatttg 1680

ggttcgttgg ttttgaatct ctctgagaga gaggtgttgt acctgaagct tcatgattat 1740 Page 16

37324PCT_CRF_sequencelisting 19 Apr 2022

gctaccgaat tgctcaagta cctcttggaa gcctacgccc aaatgccaga ggaatgggac 1800

gatgaagtaa ttggtttcag atcttcctcg tgtcatcgtg cgaaagcatc tcatcatggt 1860

aaggatcctc atcatgaggg aagacgccat cacggaaaag gattccattc taaaggaggg 1920

cctcatcatg gggaacgcca tcacggaaaa ggattccacg ctgaaggggg accccaccat 1980 2022202534

gagaaaggac cgcatcacga aaaagggctc cacgtcgaag gagagcccca tcatcagaaa 2040

ggacctcact ttgaaaaagg attccatcat gacatggaga tgtaccataa gaaattggct 2100

catcacggta aagaacccaa gacgaagcta aagcacttga agaaacaagt tgagagttta 2160

atcatcgatt tcgccaatac cactcaaaca tatgacgctt acactgactt ccttcagaag 2220

caacatgaga ttagggattc tctttcattc tgggagaaaa tcaagctaca ttttaagatc 2280

aaggcagcta acttcaaact taaatatttt gagcgagttt tccttcatga aaatggctta 2340

aagaacagag aatggttcaa acatattgta tatgctgcag gaaggaacac tggttacgcc 2400

ggacaaagac tgcctggtct tgtggaagcc attgaagaca agaatctgca tgatgcagta 2460

aaatggcttc acatcctttc caagaagatt gatagtctac agaagtcatt agagtag 2517

<210> 14 <211> 888 <212> DNA <213> Pichia pastoris

<400> 14 atgagattac ttcacatttc attgctatca attatctcag tattgaccaa ggccaacgct 60

gaatgttgtt acaccaacac acatactacc actgaagtct ggtatactac agtatatgct 120

cgagatgtta gtgaagagac ttcttccaca ctggctggtg gaagtgcaac tgtcagctca 180

gaagtgagtt cgacaattga atctagcgtt gccacttccg ctaccaccga atcttcaagt 240

gagacatcag ggtccacatc tgggtccaca tctgccactg aatcatcaac tggtagtagc 300

tcgctagcaa ccagttcatc gataaccagt tcagagtctt ccaccattac acaaaccaca 360

ggacaagagt caacaagccc aaccccatcg tcctcagaga caggttcttc tactactact 420

ccctacgata taagtccaac ggcaagttcc gactttgatg cttttaaata tcaaattctt 480

gatgaacaca acataaaaag agctctacat ggagttgacg gattagagtg ggatgaagaa 540

Page 17

37324PCT_CRF_sequencelisting 19 Apr 2022

gtatatgctg ccgcccaagc atatgctgac gcatacactt gtgacggaac cttggttcac 600

tctggaaata gtctgtacgg agaaaactta gcgtatggtt actcaaccag agggactgtt 660

gatgcctggt acagtgaaat tgaatattat gactttaata acccaggtta taccccaggt 720

gttggacatt tcactcaagt agtttggaaa agcaccacaa agctcggctg cgctttcaag 780

tactgcaatg actattacgg agcctacgtg gtatgcaact actcaccacc aggaaattat 840 2022202534

gtcaacgagg gatacttcga agccaatgtg ttaccactgg tagattaa 888

<210> 15 <211> 681 <212> DNA <213> Pichia pastoris

<400> 15 atgagttatc ccctaggtct gggtcgtaca gcttataggt tcatcccgag gtcaatctgt 60

tcaagacgat ccatctcatc ccatgcatta cctccaacgc cctccaactc accaccagca 120

ggagatttat tcaccaaact gctgaacgaa cgcatcatat atttagcagg aggcattgat 180

gatgcgcaag caacatctat cacggctcaa ttgctgtatc tggaatcgca gtcaacgtcg 240

aaacaaatca acatttacat caactcacca ggaggttctg tcacggcagg gctggccatc 300

tacgacacaa tccagtatat ccgagcgcca gtttccacgg tttgcttagg acaggcatgc 360

tccatggcat ccctcttgct tgcaagcgga acgcatggca aacgtttgat cttgccaaac 420

gctaccataa tggtgcatca accatcttcg gcaaacggaa ttaagggaca ggccactgat 480

atcgagatat atgcccgtca tatcatcaat accaaacaga aattgcaaac tttataccta 540

aaacacatgt ctccaaccat gacggtggat gaaatcactg cacttttgga gagagatcgg 600

ttcatggagc cagaggaggc agtgtctctt ggactggcgg accgtgtatt agagaggaaa 660

cccccggttg tatctgacta a 681

<210> 16 <211> 1659 <212> DNA <213> Pichia pastoris

<400> 16 atgacagata ccaaggagtt agccacgttg ctggagaact tgttgaaatt gcaaaaatca 60

Page 18

37324PCT_CRF_sequencelisting 19 Apr 2022

ggaagtcttg gtgaaattgt gggtcaagca cagcgcattt atcatgacat ttctgacctc 120

tcagtcctat ctggattatc aaccccagaa gtgctctctc ctcacacatc tccagatgtc 180

cccgagagag ttccatctga agtcaactta gacaattcca atctggcaac tgatgtcaac 240

gaaaaggaga agtattttga cgattttgca aatgactaca tcgagtttac ctacaagaac 300

cccaccacct accatttggt gcaatctgtg gcggaattgt tgaagaaaag cggattcgaa 360 2022202534

tatcttcctg aagcagctga ctggtccaaa ttattcgacc ctgaaaagac gggagcgtat 420

ttcacaatcc ggaatggaac ctctttagct gccttcacaa ttggtagttt ctggtcccca 480

gccaagggag taggagctat cggaagtcac atcgatgctc tcacaactaa gctgaagcca 540

gtctccaata agagtaaggt tgatggctac gagttgttgg gagtttcccc ctatgctggt 600

gctttgtctg acgtctggtg ggatagagat ttgggtattg gtggaagagt aatttacaaa 660

aatgaatctt ccggcaagct ttccaccact ttggttaaca gtacacctca tcctgttgct 720

catattccaa ctttggcccc tcattttggt actccctcca acggtccatt caacaaggaa 780

acccaagcag ttcccgttgt aggattttct gacggaaacg acgaggagaa acccactgag 840

gatgaacaaa agtctccttt gattggtaag cattctttaa aactactccg ctacatatct 900

aagctagcag gagtgccagt gtcctccttg attgatttcg atttggacat attcgatgtc 960

caaaaaggta ctaggggcgg tctttccaat gagttcattt acgccccaag agtggatgat 1020

cgtatttgtt cttactctgc tctacaagcg cttatcagac gtcacaagga tcccgaatcc 1080

tttgtcacag acgactcttt caatcttgtt gccctttatg acaacgagga gatcggatct 1140

ctctccagac agggagccaa gggtggtcta cttgagtcga ccatttccag agcaatcgct 1200

gcattgaaaa tttcagagcc agggactctg caaagactat atgcaaattc agtgattctt 1260

tctgcagatg tcacacattt gttaaatccc aatttcaccg aagtgtactt ggagcaccac 1320

aagccactgc caaacacagg gattgcactt gcgctggatt cgaatggcca tatggccaca 1380

gatttgttag gcaaggtcgt tgttgagcag ctggctaaac tcaatgatga taaagtgcag 1440

tacttccaga ttcggaacga ttcaaggtct ggagggacca ttggacccag tatttccagt 1500

agtactggcg ctagaaccat tgatcttgga attccccaat tgtccatgca cagtattcgt 1560

gctaccgtgg gatacaaaga tgttggcctc gctgtcaagt ttttccaagg gttctttaaa 1620

Page 19

37324PCT_CRF_sequencelisting 19 Apr 2022

aattggagaa aagttgtcga cggcattgaa gagttttaa 1659

<210> 17 <211> 3552 <212> DNA <213> Pichia pastoris

<400> 17 2022202534

atgacttcgg tatttttggg tgtttataga gccctatttg attaccaagc tcaaaatgac 60

gaagaactaa ctgtgcatga gaatgatcta ctatacgtat tggaaaagtc cgaaattgat 120

gactggtgga aagttaaaca acgagttatc ggagttaatg tcgaggaacc aataggtctg 180

gtacccagta cttatattga gcctgctaca cctatcgggt cagctgttgc actgtatgat 240

tatgacagac aaacagaaga agaaattact ttcaaggaga atgacacctt tgacgtgtac 300

gacaccgacg atcaggagtg gatcttggtt ggcctgaaca atatccattt tggtttcgtg 360

cctgcaaact acatacaaat ttctttgggt acgacggcac ctgcttctaa caatccacca 420

atacttagtc ccgccagctt ccctccacct cctcaacgga tcaacaactc ctctgttccc 480

tctctcaaag atgctgaacc agcaagaaat ctagaggacg ataatgctta tgaagaggag 540

gaagatgtac ctccaccaat gccaacgcga ccaactgcca ctacagctac atctaatatc 600

tctgctcctc aggactctga atccgaagag gaaccttcta gtagtagcag aaggccaagt 660

ggccgttcaa gggcggatga tgattttgta aaaggagact atttcacttg ggatgttcag 720

gaaattaatg gccgcaaaaa gaggaaagct gtcctgggta tcggaaatgg tagtatttat 780

gtccaagcag agggacattc ttctaagaaa tgggatatca ggaatttgac aaatttcagt 840

aacgaaaaaa agcacgtctt ttttgacttt accaacccct cggcatccta tgaacttcat 900

gcaggctcca aggacgcagc agatgccatc ctgtcaattg ttggtgattt gaaaggtgct 960

tcttcaatgc gtgctttgaa agaggtgaag gctgcatctt ctgccccaaa aaccaagact 1020

ggtaaagtca gttacaactt cgatgctgaa agtcccgatg agttgtcgat tagggagggt 1080

gatgttgtct acatattgaa cgataaagaa tcctctgagt ggtggatagt tcaggacgtt 1140

aatactaaca agaaaggtgt tgttccagct agctacatag agttgattag cgggggtgga 1200

tctactttag ccagcattgg ctcttctatt tccaaaggtt ctaagaaagc ttttggatcc 1260

tccagaaaac gtaaggaaaa agagcgtaag catttggaag agcaacgtgc cgctaaaaga 1320 Page 20

37324PCT_CRF_sequencelisting 19 Apr 2022

gaaaccgaaa gggaacgtca aagacttcga tccaaggaag aaagggatag gctaagaaag 1380

ttagatgaaa aggaaagaag gaaaaagcaa aaagctactc cacaggatga agaccaaccc 1440

gagactagca aacctaatcc tcatagagtg cgtacctgga ttgacagttc aggatccttc 1500

aaagttgaag cagagtattt gggagttgtt gacggtaaga ttcatctgca taaaacaaac 1560 2022202534

ggtgtaaaga ttgccgtagc ggctcctaag ttgtcactag aggatttaga gtatgtggaa 1620

agaatcactg gaatgtcgtt agaaaaatac aagccaaagc caaaatctag tggttcctat 1680

tccagacctt ccaaaaagcc atcctctaga gaatcttcac caaaggagtc cagccgctcc 1740

ggagttaaac aatcagttcc caagattgat cctcccaaag acccagatta tgattggttt 1800

caatttttct tgggttgcga tattgatccg aataattgtc agcgatacag tgtggttttc 1860

attaatgaac aactggatga gagtagtttg caagacctca ctccatccct actaagatcg 1920

ctagggttaa gagaaggtga tattttgaga gttcaaaaat tcttggataa caagtttggt 1980

cgaaccaaag ctcaagaatc tgctaccaat ggtggtttat ttaccaagag tgatggtaca 2040

ttgaagaaca ataggtccac tgatgttcta acaagtacag ttgtaacgcg agaaacttta 2100

agtcctacta aggccgaggc taagagcaaa agaattgatg acgaagcatg ggctctcaaa 2160

cccgctgccg aatctagctc tcaaatggat caattctcca gacctgtcag tgcaatgagc 2220

aaacaattga ctggatccat acaagatctc gtcaacttga aacctttggg ggacaatgca 2280

aacaacgctt cggtagccca caaagctgaa acaccaaaca ctacccagga caaaccttct 2340

gctcctgtct tggaacctgt gaagactgga gctgcaaggg gacctgtgca agcgcaacca 2400

acaagtggtg gtttcgtcac tgcacaacct actggtgctc tagttgcaat gcctacaggt 2460

ttcatgccca ttacgatggt gcccgtaaag acaggaggaa ctatagctct tcaacccact 2520

ggtggattcg tttcgttgca aagaactggt ggggtacttc cgcaggttac agggggactt 2580

gttcccgttc agactggtgg gttagtaatg cctcagacct catttggtgt aactccaact 2640

ttgcagccaa caggagggat tctacctgct cagaggacag gtggattggt tcctgttcaa 2700

aggacggggg ggctaattcc cgtccaacaa actggaagat tagttcctgt tcaacaaact 2760

ggaggattga ttcctgttca aaggactgga ggattagttc ccgttcagag aactggaaac 2820

ttacaacctg tacctacaac ctcttttgga agtcaaccaa caggaacttt tgtgcctcaa 2880 Page 21

37324PCT_CRF_sequencelisting 19 Apr 2022

tcttcctttg gtaatcagtt ggccaccaat ttgaataacc cgcaaaccac attcggctct 2940

caaccaacag gaggtttccc tcagacatca tttgcacaaa atcagtttag acaatcgaca 3000

ggaggtttcc agcagacccc aattgtgcaa caaacagggg gattccccca atactccgct 3060

ggacaacaga cggtaggatt ccctcagaac tcttttggac agcagacagg aggaattgcc 3120 2022202534

caaaactcat ttggacaaca gacaggaggt tatcaaacag gttttcaagg aaatggatcg 3180

attccaatgc cccagtcctc attcggtgct tcaaatctgg gattcaatgg tgctacgcag 3240

cagaactaca acattggcat gggccaatct ttgccagcag cttctatccc tccccttcaa 3300

ccctcttaca cctcatcact caatggaatg tcaaacatgc ttcagaacgt aagcatctct 3360

cagcagccac aacaagccca gccaatgacg acttttggag cacctgtggc ccagcctccg 3420

ttacaggctc aaccaactgg ctttggtttt ggtaactcgc cctatggagg tcagaaccca 3480

ctccaatctc agccaacagg taaaagagcc aacttatcag cagctaccgc agacaaccca 3540

ttcggcttct ag 3552

<210> 18 <211> 1662 <212> DNA <213> Pichia pastoris

<400> 18 atgaccaacc aatcaacagt ggtggattta cgcctttcat ccaagagagt tgttggcaaa 60

ccagtcaagt tgcccacagt cctagcgtgc tcagggtcag attcttccgg tggtgcaggg 120

atcgaagcag atatcaaatc catcacggct tttgggtgct atgcgctaac agcaattaca 180

tctttaactg cccagaatac caaaggtgtc accagtatag aaaacaccga cccaaagttt 240

ttcgaagaga ttttagaggc aaattttgag gacattgaaa tcgatgtggt gaaaactgga 300

ctgttaaacc ctgagtcatc tcgtttattg ctgaaatttt tagataaata ccacaaagga 360

aagccatttg tcctggatcc ggtcttagtg gctacgtctg gttcaatgct tgcagatcaa 420

cacgaattag ggttcaccat tgattctcat tttaagaaag ctactatcat tactccaaat 480

ttcgaagagg catgtgtgat ctactcttac ttgaaaaagc tgaagactgt agatgagttg 540

ggtgaaatag aaactttaga ggatttgaaa ggaatggcca agttcatcca gcaaactaca 600

Page 22

37324PCT_CRF_sequencelisting 19 Apr 2022

cattgcaact ctgttcttct taaaggtggc catattccct ggaatagaaa cgagcagttg 660

gttaaaaaaa agggaggaga tccagcatac attactgata ttctttatca gggtcatttg 720

gataaattca cggtaatcaa gacagattac ttgacaagtt ctggaactca tggttctggg 780

tgtacgattg ctgcctcaat tgctgcaaac attgcccgtt cgttgaagat tgaggatgct 840

gtaatttctt cgattagata cgttcatcag gcaatttttg gagcagatga gacgctagga 900 2022202534

caaggaaaag gccctttgaa tcatgtgttt catatttctc ctcccattaa cggcacaagt 960

gctgagaata actttcttcc gttctatcca ggtcacttct tagattactt actggagcat 1020

cctttggtga gtcccatctg gaagaactac atcaaccacc catttttaga aaacgtagca 1080

acaaataagc tggctaagaa cagattcatc cactacattt gtcaagatta cgtgtatcta 1140

gcttcttatg cccgtgtcca cggcttagct gccggagttg cacctgatat tgaaagcata 1200

aaggcagaag cccatataat cgactccatc atggaagaaa tgcatagaca taaagacgta 1260

ttgaactctc gtggaattgt gaaactggat gaattaagac cctccaaggc ctgcaaacag 1320

tattccgact acctcctaaa cattgcgaag acatcagact gggtggccat aaaaatcgcc 1380

ttagcaccat gcatctttgg ctactattac gctgccattt atgctcggtc gtttatcaag 1440

gatgaagctg acgtggacga agaattcttg aattggatca atacgtatac cggtgattgg 1500

tacaaagatg ctgttgacga ggccagacag tcgctagaaa gccatatgca agctgtttct 1560

cccgtccagt tagcagagct agtcaagatc tttgcagatg tctgtcaatt ggaggtgaac 1620

ttctggactt cgccaatgga actaccagaa caagatctat ga 1662

<210> 19 <211> 1008 <212> DNA <213> Pichia pastoris

<400> 19 atgcctacag tggtgactaa cgagtcctct ctcttgcaaa caaccgtgag tgttgcacca 60

ttggtgcttt tatctgttgt tgatcactac gaacgagtgg tgcaggcacc caacgcccca 120

actaattcaa acgacaaaag agtcgtgggg gtcattttgg gagacaatac aaacaagaac 180

ttgatcaagg taaccaactc atttgccatc ccgtttgaag aagacgaaaa gaacagggat 240

atttggtttt tggatcacga cttcatcgaa tcgatgatgg aaatgttcaa gaagattaat 300 Page 23

37324PCT_CRF_sequencelisting 19 Apr 2022

gccaaagaaa gacttattgg atggtaccac tctggaccaa agttaaagtc atctgatcta 360

caaatcaacg agttattcaa gagattcact ccaaatcctt tgcttttgat tgtggatgta 420

aattccaccg atatagtcga tattcctaca gactcatatt tggcaattga agaaattaga 480

gacgatggct caagtgcaga aaaaacgttt atccatttac catccatcat ccaggccgaa 540 2022202534

gaagcagaag aaattggagt ggagcatctt ctgagggata tccgagacca ggcgtgcgga 600

aatctgtcca taagattgac taacaatttc aaatcgctga agtctttaaa cgatcgcata 660

gccaacattg tccaatattt gcgcaagatt ttaagtggag aattaccaat aaataatgta 720

attcttggaa aattacagga catattcaac ttattgccca acttggttgc cgttcaaggt 780

gatcccacaa aaccagccac tgcaagtgct aaccaactag ccacatcatt caatgtgaag 840

accaatgatg aattaatgat ggtttacatc tccagtttag taagatccat cttggctttc 900

catgatttga tcgacaataa gatcgagaac aagaagaaca acgagaaaga taaggaattc 960

acaccaacag aggaagaacc ccaacaagcg gctatagaat cgaaataa 1008

<210> 20 <211> 969 <212> DNA <213> Pichia pastoris

<400> 20 atgacaatgt caaccgaaga tatcatcgcc aggcatagga aggagaaaag ggaccaaatt 60

gcacttatta caaggatgaa gaagcagagc actaagtcaa ccaaaaagga aatcatgaaa 120

caatgctctc tcttggaaga agagctacag gcaagacata agaaggagtt aggtgagtgc 180

aagactgaaa attccgtcga gagaagtagt gagcctactg acgaaaaatc aaatggtgga 240

gaactttttt cccctgaaaa gttattatca atgatgactt taaaacagca aggaactcca 300

agtgagaatc aaggaaacgc aactgttcca aagagaaaac gcaataggca gaaggacaga 360

ttagctagaa gggaagttgc cattaaagag atgcaagcag cagcagcaaa agaggctaac 420

ctccaaacaa atttcaaaga gatagaattg aacaacataa gccaactgtg ccaagttgct 480

cacctggaac catatgatat ccgacctgat gggcattgct tgtttgcatc tataaaagat 540

cagttggagg ttcggcacaa aattgaaaat ataagtatac aagatcttcg gtctctggct 600

Page 24

37324PCT_CRF_sequencelisting 19 Apr 2022

gcgagtcata ttaaaaatga tcccgagact tatactcctt tcctttttga tgagaatact 660

atgaaaatca gggacattga tgactatgca aacgagctgg aaaccacggc tttatgggga 720

ggtgatatgg aaattttggc attgagcaaa gagtttgatt gtccaatcag tgtaatgatt 780

agtggaagac ctattcatct tgtcaatgcc gacggttcta aagaggagtt gaagttggtt 840

tattaccgtc atgcatatgg cctaggtgag cattacaact ctttaagaga tagatcagag 900 2022202534

ataagggagt cttgtatagt tgagcaagag gaaaaagaag cggtagacga tggaaaatca 960

tcttcttga 969

<210> 21 <211> 939 <212> DNA <213> Pichia pastoris

<400> 21 atgagactta agatcaagcg ttcaaatgaa cagcggctaa taacattgcc tgacggggct 60

acagtatcgg atttacttaa tgaaattgga tcagcttcta tcaatataaa ggttgggttt 120

cctcctcaga caattgatat ctcagatacc agcaagttgc ttactgatag tggaatcaag 180

aatggtgaaa tgatcattgt cactgatacc attgaaacag aagtgcctgt caacaagaat 240

gaggttgcaa ttgccactgt ctcaaaccag aatgatgcgc cctacgttca aatagacgac 300

atcttcctag tcttgcggaa gattcccgat gataattctt gtttcttcaa ctctgtcggc 360

tactgtatat ttggtcctga ttcaatcaag tatccggatt ctcaacaaga actaagacag 420

gccgtcgcta atgtaatcag agagaacaac caaggtattt ataactccgc catcttgggt 480

ggaaagtcaa tcacagagta ttctcagtgg atccaaagca gtaattcctg gggaggagcc 540

atcgaagcac agatattggc agaatacctt gatatcagta tctggacagt ggatattgag 600

tctcttcaag tctacaaatt taatgatgaa atggcttcaa ggttttgcgt tattatgtat 660

agtggtattc attacgacgc tatggctctc aagctggaca catcattaga tgaggaggac 720

tcacaaattt gtgtgtttga taagttcagt gagttgggga ctttgattga agacaacgtt 780

ctcaaattaa ccaaccatct taagaaccag ggctattata cgaatacttc cacattcata 840

ctccaatgtc aaatatgtct cgcaacattg caaggagaaa aagaagcaaa tagccacgca 900

aagaaaactg gccacacaaa ttttggtgaa gtcaattga 939 Page 25

37324PCT_CRF_sequencelisting 19 Apr 2022

<210> 22 <211> 5528 <212> DNA <213> Pichia pastoris

<400> 22 atgtcattgt ctgatcctga ggacagccta agacgtctac ttgtgagttt accctccaat 60 2022202534

gttaagtacg atgcggagtc ttcggtattg aaaagccgac tgaaccttgc tctatatttc 120

tcgctgacaa agagaggtga atatctgggt tccttggtaa cggacttgcc aatggatttg 180

ccatcatctt attccgaaat cttagaggct gaagatgatt cctactcaag attggctgaa 240

tcaatgtaca aatgccctaa ctataagcat catggaagac cttgtgcaag gcagttcaag 300

caaggagagc cgatataccg gtgctacgaa tgtggttttg acgagacttg tgtaatgtgc 360

atgcattgtt ttaataggga gcaacatcga gaccacgagg tttccatttc aattgcttcg 420

tcctccaacg atggtatctg tgattgtgga gatcctcagg catggaatat cgaattacac 480

tgccagagtg aactggaaca agatgaccat tcaagttcag aagttaatcc agattttaaa 540

tctgctataa gggaaacaat ggatattatt ttagattaca ttttggattg tactattcat 600

tctgcatcta tgcttcctgc tgttcaggac atgatgaagg aagacccatc cgactatgaa 660

atggctattc aatatgcttc agatagttct tctctgccca ttgaaagata tggagtggaa 720

gacacgaatg ttcagtcctg gaacgtagtc ctgtggaacg acgaattcca taattatgat 780

gaggctattg attgcatcca gcaagttagt agatgttcat tgtctaaagg acaagctgac 840

gctcaaaaga ttaatgattt tggattttcc atcataagaa gaagtgaatc cttgccttta 900

ctgatagaaa ggtgcgccaa ggttgaagaa tccgggttta ctattacgat tctttctgat 960

agagatgtta cccgattgat tattattgat actatttttg attggttatt gactctgtta 1020

gaaatttcaa ggccggaaat tcagactgct attagagaaa gtttgtgtga atctcttttg 1080

gaagagtttc atgccgacat tcacgaagga gattttttct accgggaaga tgaatattca 1140

gacacacggg gtttgctgga tttcaaaaac agaattccag ccccattggt ggaggatgta 1200

atgaacgagt tgtctattga tgacttgaag aacagaaaac tatccagttt tcttaatgaa 1260

caaccttcag ctctagtcgg ctcaagagta cagtatttct tctatatgga tctgcggttc 1320

Page 26

37324PCT_CRF_sequencelisting 19 Apr 2022

tggaaaaagg caagaaaatc tttgaaattg ctaacgacat ctgttttggt ttcaaacttg 1380

gaatacaaaa agactttttc tgaacagttt gtgaaaatat actcgcatct gttgatattg 1440

atggcaaagg aagatagaga gtggcttctc agcaatgcgg gcaatgctgt agtacaactc 1500

tttacatgtc ctaaaacatc tctccattta ttacaaccac aatatttcag aagcatcatc 1560

gtccccatca ttttgttgtt cgaatcttat actggaaacc atttgctgtg gaaacgacca 1620 2022202534

tatcaactct tatcacgtaa gaaaggtctc aaatttggtt taatgcgttc tttaactgat 1680

ctagtgacgt taatcaccac tgcccatcaa tcagaagaac atttggtact ttttcagggt 1740

aagaacttca tttacataat catgcttttt aggatgttcc agagtgccct gacattggtc 1800

agaaaggaag gagaacatat taccagggaa tccactgaat ttttaaccta cctgcaaata 1860

tcttactacc ttaatgatgt catcaaaggt attgttgaaa ttgcgcaggt tcctgaaata 1920

cgtaaacctg aacattggaa agttgtggaa acaaacatac aaatattggc cactttaatt 1980

tcatcagaac cttataagtt tcatatggtg cacgaaaaac aacttattga ccatgacgta 2040

acaaagaaac caacctctct tattaatcca ttgaatggat tactgtctaa catgttaaca 2100

accgtaaggg ccaattcttt ttcattttta actcgtcaag tttctcagat taatttttgg 2160

agtatcaatc ccgaagtctc attttcagat gatttagact atctgaaact ctcatcgaag 2220

agtttagaag caattacttt gagttcacag ataaaaattg gccactggat tagaaatgga 2280

tccatgacta gtaaacaagc gcaattgtac tgcacgaggt tcactcaata tggttacata 2340

gccgacgttc atttgaacca acttgctata ctcgaagaac gcgacgatga tcgtctatta 2400

ttaaacattt tggatagatt caatctaata gattggttct ataacgatca ggacgtgctt 2460

ggtactgttt tcgaagaacg atctttttac ctaatgaatg aattggttaa gtttctttat 2520

aatatgtttt cacacagagt taacttccag tttgaatcaa atttcacaga gaaaacccag 2580

tatgaggtaa cgcaatacat tttatacacg ctttgtaaag gatctttgtc attttcagat 2640

ctgacagccg actttcctat ctccgtggaa gttactgttt ttgacaagat ccttgatgag 2700

gttgctgttt acgaagagcc caaaactatg aatgattctg gaaagtattc tatcaagaaa 2760

agttattaca aaaagatgga tccaatgtct atttatgtgg actcgggtga tttcgatgat 2820

gtatcaacag cgatagtaaa ggaactttca attttaggaa aaataaaaga ggagaatgtt 2880

Page 27

37324PCT_CRF_sequencelisting 19 Apr 2022

gtaattgaac ctcagatcag tggaccgaat gaatccaaca gccgtgtctt gagcagattg 2940

aaacggttct tcattagcaa atctgtagtc aaactgtttt ataaattgtt acaatctgct 3000

ctttctgaga gcaatgagac ctacgtcatt gaacttttac atttgattca agcagtttta 3060

ttagatgaac atgaattgta cagaatcgaa gatccagtgc aatactttat tcaaattcct 3120

gtgtgtgatc tactgttatc agttgttgag cacaatgatt tttcacgacc tgtctgcaaa 3180 2022202534

aaactgaagt tctattgaat tggttgatcc agcgggacga gtcaatcatt gactcattgg 3240

ttgattcttt tggtgaaaag cacattgaaa actttaaaaa atctaaggga tctcaagttc 3300

tggagactaa acgagctaaa caaaagcgtt tagccaagga gagacaagag aagatcaaat 3360

cacgatttgc taaacagcaa aagtctttca tgaagcagaa tttggacgca aaaaagagtg 3420

cggaacatgt aactacacat ttatccaaag acaatgaagg attaggtagt tcctcccagg 3480

actcttttca tgagtgcatt ctttgtcaac gtgctcagga gggcaacgag atgtttggaa 3540

tccctgcata tgttgaaaaa gtttccacgt tttgggattt tcaacctaag gatgagtcaa 3600

cctatacgga aagatgctta acaaccattg aaaatcaaat gaaacaattg catgaagaaa 3660

cggatgccaa caatgaggtt agagaacatc tttattatca aaaagatact cctgtaaaaa 3720

gcatggcacc gatatcttca agacacattg ttaagtcatg cgggcaccac atgcattata 3780

aatgtttttc tgagttacta gaaaacagca ggaagtttag cacttgtccg ctttgtcgct 3840

ctgccattaa tgcttttgtt ccacaatttg ccatgaaaaa cgatgctagc cctgcttttc 3900

aggaggctgc ttcgaatatt agtcactttg aaaagttgaa tttgaatcaa attgtatcga 3960

aatatcttct caatgattcc ttcttgaaat ttattgcgga agaaagtaag gaccagttca 4020

tgtatttgaa tgagtttaaa gacattttga aagacgcccc agatgcttct gaccacatgt 4080

tgagtgaagg gttatttccc tcatttttgg ccatgtcaac attattgggt aataccctag 4140

caaatactga aattcgtctc agattatccc ccgagaagat tccccagaaa ggaaacttga 4200

agagaaaaga ttcggaatta ataacctcat tacttcaatg tgtctcggtt atctcaatct 4260

tattgaaaca atcttatcct gaagagcagt atctgtctcc atttttgaat aaaccaaatt 4320

cattaattat tgattttgcc atttcacttc tacttggaaa agaagactca cttcaagaaa 4380

ctattgtggg catttacaag caaacaattc tgcattcatt gaatttacta ttgactaacg 4440

Page 28

37324PCT_CRF_sequencelisting 19 Apr 2022

ttggagataa tgagcatttc agaaggatgc tgagcggtgc aaactctatt attaatgatt 4500

cagaactggc cattttcaaa aagtttgtgt caacggccac ttttacctct gatgtttcat 4560

tcattacttg caacgaacaa ttattggttg gactgtatat tcttttggag aaaaccacca 4620

cagtgtatct taaacagttg tttctgataa tcagcatgtg cagacccttg gacttatgcc 4680

taaatcgtga ctacgagaat tccaatgatt acgaccacta tttgtttggc caactgtgca 4740 2022202534

aattttttaa cctttccagt ataatcagtt atttgggatc tggaattcct ggtggaaacc 4800

tattggagga gcaaaatgat cttatattaa aaggacaatc cactctccct tcaacaattg 4860

agtatccagg tctcgtttat cttgtgaatt tgcctagaga actgaacact tttacttttt 4920

caaaatatga cacccaagat gcagttaatc taaacttttc tgtttgttta acgtgtggca 4980

aaagagtgaa acatagcggt gattctgaaa atgaaattga aaacttccct gggtacaatg 5040

gtgttcctct tactttgttt caccatcata agaattgtcc tttctctgga tatggagaag 5100

cacaatgtat cttcttaacc ccaaagttga ataaattgac tgccttacta aagattcagc 5160

ctccacgagg aatttctgat cgctcgctat atcacagtac atttgcattc ccattgagca 5220

gcccatatct aaccacacat ggagagtcac attctggtca tggaggcttg atacgcaaag 5280

cgttcctgaa tagagatcga tttcgaaatc tgaatgagct atggttggat ggtgaactag 5340

ctttgtatat ttcccgaagc cttggggatt ctcaaattgt agcggaacca atcaaccctg 5400

ttatgattac aatgccggga ggtattcagg aggcattaaa tcttgcgttc accactttcc 5460

tcggtgacca agaacccggg gatgatgact tggaagatta tgagtatgac atactgttaa 5520

atagatga 5528

<210> 23 <211> 3168 <212> DNA <213> Pichia pastoris

<400> 23 atgtctgcct ttggtgtggt tccgagtgta ttaaacactg gaaaccagat caagcagaaa 60

aacggaacgc ttttcaagaa atcttctgga gtttacaata aacagcagcg ggatcacaat 120

tccagggata aaaagcgatc agctcgtaaa acaaatacac cgccaacacc gactgagagt 180

acttccgcaa agaagtcatc aactcaatca gacgacaaag tgagtcctga tattttacaa 240 Page 29

37324PCT_CRF_sequencelisting 19 Apr 2022

ttgtcgcata ttgagattca atatgtgggc ccacttcttt ccaacccaga atctttggga 300

tatgtgaaac aaaacaataa taccaaaatc aagactccga aatatttagt ggatacagat 360

tcaaacctgg tttttggtcc tgatacaact aataaatggg atattgagaa ccagcacaaa 420

atgatcgaaa tggaatcttc ccatcaaggt gactggcaag gtatttatga acaatttcaa 480 2022202534

gaaatgaata aagtggagcg tcaaaaaatg gaagatctgg gcttggtggc aaaagaggga 540

caaagcatgg acctgacaaa tgctatctca ttcaaaggta gctgcgtgga tatgtgtccc 600

gtttatgata gagtcaagag ggaggtacag agagatgttg atccattgga gagagatcct 660

gccactggta agatatctcg agagagagct ttaaagaaat ttgtgcgtcc ttcaggccaa 720

gcaccgcctc ttccttctga cgtaagacct cctcatattc tggtaaaaag tttaaactat 780

attgtggata atttgctgga taaattaccg caaagtcatt cattaatttg ggatagaacc 840

cgtagtatca gacaagattt tacactacag agctactctg gcttggaagc aattgagtgt 900

aacgaaagaa tttgtcgcat acatctactt tgtgctcata taatgccggg ttctgatcaa 960

tctgacttct ccaagcagca agaaattgaa caattcacaa aatcattgaa aacattaaca 1020

gacatatatg atgttgtcag atccaaagga ggaaaatgtg ccaacgaagc tgaattcagg 1080

gcttataatt tgctggtgca ttttcgggac ccaaatctaa ttcatgaaat ccagaactta 1140

cctactcgaa ttcttaagga cgaacgagtt caacttgctt taatgtttcg aagtctacta 1200

ttgaataata atttcaaaga ataccagagg aacattcctg gttgcttggg ggtttttcag 1260

cagtttttca atatgtgttt tgatccagcc accccattct taatcggatg tgtgctggaa 1320

cttaattttg aagagataag attttacgct ttgaaatcga tctcacgttc ttatcacaag 1380

aaatctgccc ctctaacgac ccagaagtta gcatctatgc tcggatttga ttccgaggat 1440

aagctcctaa ctttcactaa ttatttcaag actcctacgt gtactaattc tagaaatgaa 1500

acgtgcattg atatctcaaa acttagatac gagagtttta cggatttggc tgctccaaag 1560

cagatttaca cttcaagatt agacaacaaa ttaaaaggat tcacctataa ggatgttgtt 1620

gatcaaggat taaataacac atccttgcac atagctaatt tgaaagaaac aatggctcag 1680

aatcaacata ttgcagtgga gaaattaccc aatatctcat ttccacaaca tgctttgtct 1740

tctacccctt tcgaagtaga atcaaagtca gacatagtca gatcttcttc cggatcggct 1800 Page 30

37324PCT_CRF_sequencelisting 19 Apr 2022

ccgccccaga ctttgatccc accgattcaa gaaaaagtaa taacttctca aatacagcca 1860

ccaataactc ccgtcgttcc cactgaagaa atccaaactc ttccaaaaat agaggagccc 1920

aggttcaaag atcttccaaa ttttgaaaat gcatgcaaag aggtttcctc tattttaatc 1980

aagaagacta tatctccttt gattgctccc atagtgaaca atcagctaga agagtacaac 2040 2022202534

cggcgacaaa cggttttaag ggatcaggag agacaaaatc aaagaagaca acttttgatt 2100

tcatcccttc aggaagaatt gtactctgct tttatacgag aacaagtgta tattcaagtg 2160

gttgatactc aagccaaaga gtgctttaac aagaatctga aacggcgaat atttcagaaa 2220

ttcatcgggg gtttaattac attgaaaaac aaacaaatga ataagagaag aaaacttgat 2280

gaaattcaag tcttcaagaa taaggttgtt tcctcaagtc aacttcggta ttcagtttca 2340

agaagtcaaa cggaggacaa ttcaacgtca aactcgagtg acgaggaagc atcagctgtt 2400

cagatgaata ttactctttc accatctgtg gatccacttt ggtcacccat agatattaag 2460

tttatattag actccaattt aaagttgttt gaggataaca aggataaata ctggaatttc 2520

atgtttgcga ttgccgattg gactattcta ccaagcaaat ggcttcgtta caaattccaa 2580

cttcaaaacc ccagtctcat aaatactgtt gaatcctcaa attacaaagc caaattacgg 2640

gctctaccca gtgacaaact tcttacaagg gaatacatgg agcactgtcg atttttggta 2700

tttcaagtcg gaaaggttga tgaatcatca aacctgaaag aatctttgtt cagagactca 2760

cagtttatta accgattaat gaaatatgcc aagaagtact cgcaatacca gattggagta 2820

cttgtcttat attatcatga ggatgactct tttgataaac agaaaattat tgatcttttg 2880

ttattagaac aatacacaaa taagttagtc aactcactcg agatagttga catgaacaaa 2940

ctcacaaatg atgaactgat aaaagcattg accacgctag tccacaacta taaggataaa 3000

ggtatcaaca aatcggtacc aacatcttcc accaaaggac acaccactag cattatggaa 3060

caggatatga cagtatacag ctacagcacg tccaattcca gggatgctaa gcttaattat 3120

attttgaagc aagcctaccc ccgcaggggg tttcacttga aacaatga 3168

<210> 24 <211> 1401 <212> DNA <213> Pichia pastoris Page 31

37324PCT_CRF_sequencelisting 19 Apr 2022

<400> 24 atgtcagaat ggccctcagc tttggaaaat tttgtaagtc attgtttcca gcgtgccaac 60

attgagagct ttccacccgg caaaaaaaaa gaactccaaa aacagttgac gcaaatcatc 120

aatttagcaa ttcttgaaaa caaacttaat tctaataact ggtccaaaca aaagctacca 180

atatttggag aagcaagaga gttagaattg gagcagaaaa tgggaaatgt ttatccaatt 240 2022202534

actgtttcta gtcgaagaag tgacttgatg catcaagagg cagttcaacc atctgagcct 300

ttagttccct ccgaaagcca acaaaagaaa aagtctagag aattgcgatt taagatcact 360

aaaaaaagtt ctgtatcacc cgcaaataaa atacaagttg cttgtgactt gaattgtaaa 420

cttgtgggaa ctaacacctc tatcgagaaa gattattata gacttacatc tcatccggat 480

ccttccatgg taagaccttt gcctatttta aagaaatcgt tgcagcatct ttacgccaaa 540

tatcaaagtc tagaacgttt caaagctctc agcaaggcag agtacagcta ttttttgaat 600

caactgaaat ccctaaggca agacctcaca gtgcaagaca ttcagaatca gttcactgtt 660

aaagtttacg aatttaatac tcaattggcg attcaaaatg aagattttgg tgagcttaat 720

caatgtttga ctcagctggc gcaattgtac actgtatcaa ctatgggtca tacttattac 780

tattctgata ctggcaaata caaccaagag cacaactgtt ttcttgccaa ggatctttgt 840

gaggatcgaa accatatcaa tatgttcaaa tttacgagtt atagaatttt atattttctt 900

ctcatagacg ccccctggga attgctaaaa ataaggcagg atttattcaa ccgtggtcaa 960

cagtatgcaa ttcgtcacaa caaatttctt ttgaagtcat tcaagctttc ggatctcata 1020

accgccatgg attatattca tatcaaggac gaatattcat tcctcgtgaa tatggactca 1080

gatgtctgca atttaaggac agtgtttgat gacgaacata tgactttgaa ccaagacgac 1140

tggtttttct ataagatact ctaccataag attttcttac gagaacagct gaaggccctg 1200

ataactataa gcaaatctta tcgacagata tccctctact acttgaaaaa tctactgatg 1260

gatttagtat tcttggaaaa gaataagtta tctcgtttca ttgagaatgg tgaggtattt 1320

aactgcacga gcgcaagatc attactgctt caaatagaga agaagcagct atcaaagata 1380

gatatcaagg gtcaggtatg a 1401

<210> 25 Page 32

37324PCT_CRF_sequencelisting 19 Apr 2022

<211> 1075 <212> DNA <213> Pichia pastoris

<400> 25 atggttgact cagagactat caacaaattc atagaagtaa cgggagcctc tgccttccaa 60

gcaattcagt acctagagga gactgatgac tttgaagcgg cagtcaatga ttattattcc 120 2022202534

tctcaactgg agaatgagaa gggcaagggt aaatcagaac gtccagtcaa tcaaacaaag 180

gcttctgcag ggcccaagat cagaactttc aacgacctaa atagcaactc aaatggggac 240

aacaatcttt tcacaggtgg tgaaaagtcc ggtcttcaag ttgagaaccc agacaaacgt 300

ggggaccctt ttgggttggt caatgatctt ttgaagaaag ctgaggaaac tggccaacaa 360

ccagatacaa ggccccatga agaagctcct gctagacaat ttgttggaac tggccacaag 420

ctgggcagta cggacagtcc ctccgaagtt agtgtctgac cctgcctcaa gaataagaag 480

agctcagaaa gtcagccgac agataacatt ttggaaggac ggattccaag ttggagacgg 540

agatttatac agatatgatg accctgcaaa cgcaagatat ctagccgact tgaacgctgg 600

aagggcacca ctggctcttc tagatgtcga gattgggcaa gaggtagatg tcacagtgca 660

taaaaagata gaaaaaaatt tcactcctcc taagaaagcc cgagttggct ttcaaggtaa 720

aggtcagaga ttagggtctc cagtaccggg cgacataaag ctcagtcaat ctcctgaggt 780

gcaacaagaa acacaagagg aagctgagga ggaaaagcaa aaggaggagg ccgagcagct 840

gggaactggg gattctcccg ttcagattag actcgccaat ggtcagagaa ttgttcatag 900

attcaattct actgattctg ttgctcaatt atatgcattt gtcaatgaac atagtccctc 960

cgccagagaa tttgtgcttt ctctagcttt cccggtgaaa cctattgaga acaatgagga 1020

cacactcaag gatgctggac tcataaacgc tgttgttgtc caaagatgga aataa 1075

<210> 26 <211> 897 <212> DNA <213> Pichia pastoris

<400> 26 atgggcgtga tacttccaga cgatggtaag caatcgggag gccaaccaaa tagaagggct 60

aaagtcctga gccgattttt accaccagaa catcaaagac cttcaatcgg cctcttcctg 120

Page 33

37324PCT_CRF_sequencelisting 19 Apr 2022

ggacctttta ctccagcagc tgataatgag attgccctgt ggacttgcat tggcgctcag 180

ctctttagtg ggctggcatt gcttagaatg agccgaagat ttgttttttc gcccgatcaa 240

tctgtaagaa ggtttctctt taagactttt cataatgtgg taggtgcagc cctgatattt 300

gggagcggat tagaagggac taggatgctt ctacctgagg atccttggaa agaagaagct 360

agaaaagcaa gaatattggc ccaattgaaa ggtgagcccg ttagttggtg gtatggaccc 420 2022202534

aagagtttta ttccttctgg aaggttagaa tacacaaaac agatgcagtt tcacaacttt 480

gaagtcatgc ataaatcacc cgaaaaaata gcccgagctc tcatgattaa ggacaaactc 540

aaggaggaaa caaataccct ttattcgtcc attcatgaga aagcggaaca acagactatt 600

cgactctcta aagatctaca gaacaacgtt cccctcaaag gggtaacgtc atatgttcct 660

caatttagca cttcaaatac ggacaccaag ttatatttga aaaatgttag cttgaagacc 720

catgccgacc tggaaaaggt ctgggcagaa cacaatcctt gggacatcct ggaagagaaa 780

atttctccaa tttccgtaat tgcactgcca aagtttaacc caattatatc tgaggttgaa 840

cctgacaagc agcaaccatc tacgggtgat atcaaataca ttagtgacag aaaataa 897

<210> 27 <211> 1530 <212> DNA <213> Pichia pastoris

<400> 27 atgaaatatt tgccactcgt tgctaccctg gcctcttcgg ccctcgctgc tggcatcaac 60

ttcgcccaat tactggacca gaagccactg gacattgccg ataatgttaa atgggaattg 120

aagcctgagg tcgactctgc tgctcttcaa agtgcagtca atgagctaga cttgaaaatc 180

gaagccagct atttgtttaa agttgcacat ggttccgtct ttgaatacgg acatcctacc 240

agagtcatcg gttctcctgg tcactggtcc acaatcaacc atgtcctcga cacattacat 300

aacttcaaac actactacga cgttgacgtt cagccatttg aagcctttac cggtatcctt 360

aagtctttct cattgaccat taacggagtt gcaccaaagt ctgcagaagc tttagattta 420

actcctccta ctcctggcgg ttttccagtg accggtccag tcgttttagt tgataattat 480

ggttgtcaag cttctgacta tccattcaac gtgactaacg gaattgcctt aattcaaagg 540

ggttcttgtt cattcggtca aaaatcagaa cttgctggtc tccgtggagc caaagccgct 600 Page 34

37324PCT_CRF_sequencelisting 19 Apr 2022

ctcatttaca acaacgtgcc aggtagtgct aagggaacct taggtgcccc aactcctcat 660

caggtaccat cgttgtcact ttctcaggaa gatggagagg ccgtcaagcg tcagcttctg 720

acttctggaa gcgtaattgc aactgtcgct gtcgattcct acgttaagaa gttcaaaacc 780

aagaatgtga ttgctaccac tcgttacggt aatgatagca acattgtgat gctaggtgca 840 2022202534

cattcagact ctgttgctgc tggaccaggt atcaatgacg atggttctgg taccatctct 900

cttttgaacg tggccaaata cctaactaaa ttcaaagtta ataacaaggt tcgtttcgct 960

tggtgggcag ctgaagaaga aggattactt ggatccgact actacgtttc aaagttaacc 1020

cccaaggaga aatctcagat tcgtttgttt atggactacg atatgatggc ttcccctaac 1080

tacgcctacc aggtctataa tgccactaac agcgagaacc cagttggatc tgaggagctt 1140

aagaatttat acattgactg gtacgttgaa cagggtctga actacactct agttccattt 1200

gatggccgat ccgactatga tggattcatc aagagcggta ttcccggagg tggtattgct 1260

accggagcag aaggtttgaa gaccgaagag gaggctgaac tatttggtgg tgaagctgga 1320

gttgcatatg acccatgtta ccactctctt tgtgacgatt tggccaaccc tgactatgtt 1380

ccatgggttg tcaatactaa attaattgcc cacagtgtcg ccacttatgc aaagagcttg 1440

gacggattcc cattgcgtga ggagcctagc ccattcaaga tgactgccca gtcaaacttc 1500

aagtaccacg gtccaaaact tgtcctttag 1530

<210> 28 <211> 513 <212> DNA <213> Pichia pastoris

<400> 28 atgctcaaac actccttaaa aacagggttg gtctttctca cttggatacc ggtgatttat 60

acggtaaagg aacacctgat atacgttgga aaggtggaag gatcctcaat gtcacccact 120

ttgaatcccg ttaaaggtta ttctgactat gtgattttat ggaagttaaa cttcaaagag 180

tcactcaaag tgggagacgt ggtttttata aggtctcctg tagatccaga gaagttatat 240

gctaaacgta taaaggctgt tcaaggggat accgtggtga ctaggcatcc ataccccaaa 300

gacaaagtgt ccattccaag aaaccatctt tgggtagaag gagacaatat acacagcgtg 360

Page 35

37324PCT_CRF_sequencelisting 19 Apr 2022

gatagtaaca actttggtcc gatatcgttg ggccttgtat taggaagagc aactcacgta 420

atttttcccc tgaacaggat aggtaatatc tctggtgaag ggggtagaga agttagggag 480

gattatttaa gagcggagga cagtccgatg taa 513

<210> 29 <211> 915 2022202534

<212> DNA <213> Pichia pastoris

<400> 29 atggtttctg aaattcagct tagattagct gttattattt atgatatact ctgttcggcg 60

tcttatgttc tagtcatcca tttgagacca accagagccc ttccgcatca acccatagac 120

cgtaacaatc ctctaacgat taaagaaagg tgccagcgag ccagtgtgtt gactgctaca 180

catgtattat tattgcctat tcttttaaaa gtgttgagac tgtcagaaat tgcggaaact 240

acggcgaaac ttggaatagt ggtgggatat cacaaccaga gctggtcttt ctctaacctc 300

caagatgata ttgtcagcat tttcaaagct ttaggtttga ccatgattct cttttctggt 360

cctattgtag attattttta ctattcaaac tcaacagaag taatcaagca agatctggcg 420

tatgtcgtta gcctcgaggg tatgcgtgat ctacttgtgg gacccatcac tgaggaactt 480

ctttatcggt catgttccat ttcattaatg ctagtagcta acgattacgc caacaaattt 540

ctgttcggcc aacactggtt aataatggta tcatcactct acttcggtat agcacatctt 600

catcatgctg ttgaactgta tcattgtaaa agatattcat taactaccat aaccatatca 660

actgccttcc aatggtcata tacaacgtta tttggaatat atgcaagctt tctatacttg 720

cgaacaggat ctgtatggtc agcaatagtt gttcattcat tttgcaacat gatggggttt 780

ccccggttga catttggacg tgatgaagcg agagattgga aagtgggtta ctatgtgttg 840

ctcgctctag gttccgtcct attcaaaaag tttctttact ctctaacaga atctaaccat 900

acgcttcttc tataa 915

<210> 30 <211> 2451 <212> DNA <213> Pichia pastoris

<400> 30 Page 36

37324PCT_CRF_sequencelisting 19 Apr 2022

atgtatcccg aacacaagta tcgggagtat caacggaggg tgcccttatg gcagtactcc 60

ctgttggtga ttgtactgct atacgggtct catttgctta tcagcaccat caacttgata 120

cactataacc acaaaaatta tcatgcacac ccagtcaata gtggtatcgt tcttaatgag 180

tttgctgatg acgattcatt ctctttgaat ggcactctga acttggagaa ctggagaaat 240

ggtacctttt cccctaaatt tcattccatt cagtggaccg aaataggtca ggaagatgac 300 2022202534

cagggatatt acattctctc ttccaattcc tcttacatag taaagtcttt atccgaccca 360

gactttgaat ctgttctatt caacgagtct acaatcactt acaacggtga agaacatcat 420

gtggaagacg tcatagtgtc caataatctt caatatgcat tggtagttac ggataagaga 480

cataattggc gccattcttt ttttgcgaat tactggctgt ataaagtcaa caatcctgaa 540

caggttcagc ctttgtttga tacagatcta tcgttgaatg gtcttattag ccttgtccat 600

tggtctccgg attcttccca agttgcattt gtgttggaaa ataacatata tttgaagcat 660

cttaacaact tttctgattc aaggattgat caactaactt atgatggagg cgaaaacata 720

ttttatggca aaccagattg ggtttatgaa gaagaagtgt ttgaaagcaa ctctgctatg 780

tggtggtctc caaatggaaa gtttttatca atattgcgaa ctaatgacac ccaagtgcct 840

gtctatccta ttccatattt tgttcagtct gatgctgaaa cagctatcga tgaataccct 900

cttctgaaac acataaaata cccaaaggca ggatttccca atccagttgt tgatgtgatt 960

gtatacgatg ttcaacgcca gcacatatct aggttacctg ctggtgatcc tttctacaac 1020

gatgagaaca ttaccaatga ggacagactt atcactgaga tcatctgggt tggtgattca 1080

cggttcctga ccaagattac gaacagggaa agtgacttgt tagcatttta tctggtagac 1140

gctgaggcta acaatagtaa gctggtaaga ttccaagatg ctaagagcac caagtcttgg 1200

tttgaaattg aacacaacac attgtatatt cctaaggata cttcagtggg aagggcacaa 1260

gatggctaca tcgacaccat agatgttaac ggctacaacc atttagccta tttctcacca 1320

ccagacaacc cagaccccaa ggtcattctt acgcgtggtg attgggaagt cgttgacagt 1380

ccatctgcat ttgacttcaa aagaaatttg gtttacttta cagcaaccaa gaaatcctca 1440

atagaaagac atgtttattg tgttgggata gacgggaaac aattcaacaa tgtaactgat 1500

gtttcatcag atggatacta cagtacaagc ttttcccctg gagcaagata tgtattgcta 1560

Page 37

37324PCT_CRF_sequencelisting 19 Apr 2022

tcacaccaag gtccccgtgt accttatcaa aagatgatag atcttgtcaa aggcaccgaa 1620

gaaataatcg aatctaacga agatttgaaa gactccgttg ctttatttga tttacctgat 1680

gtcaagtacg gcgaaatcga gcttgaaaaa ggtgtcaagt caaactacgt tgagatcagg 1740

cctaagaact tcgatgaaag caaaaagtat ccggttttat tttttgtgta tggggggcca 1800

ggttcccaat tggtaacaaa gacattttct aagagtttcc agcatgttgt atcctctgag 1860 2022202534

cttgacgtca ttgttgtcac ggtggatgga agagggactg gatttaaagg tagaaaatat 1920

agatccatag tgcgggacaa cttgggtcat tatgaatccc tggaccaaat cacggcagga 1980

aaaatttggg cagcaaagcc ttacgttgat gagaatagac tggccatttg gggttggtct 2040

tatggaggtt acatgacgct aaaggtttta gaacaggata aaggtgaaac attcaaatat 2100

ggaatgtctg ttgcccctgt gacgaattgg aaattctatg attctatcta cacagaaaga 2160

tacatgcaca ctcctcagga caatccaaac tattataatt cgtcaatcca tgagattgat 2220

aatttgaagg gagtgaagag gttcttgcta atgcacggaa ctggtgacga caatgttcac 2280

ttccaaaata cactcaaagt tctagattta tttgatttac atggtcttga aaactatgat 2340

atccacgtgt tccctgatag tgatcacagt attagatatc acaacggtaa tgttatagtg 2400

tatgataagc tattccattg gattaggcgt gcattcaagg ctggcaaata a 2451

<210> 31 <211> 1866 <212> DNA <213> Pichia pastoris

<400> 31 atgaaaccgt atcaccatgc aaaaagccgc ccaataggca gctacctgta ttttggggtg 60

tttaccgtag cattgacatt tctgacgtgg cttaaatatg acgcagagct gtttgctcag 120

caggttcact cgaaagacat ttatgaccca cagttcaaca ttacgttgcc aattgatggc 180

ccaacattta ccccatcaaa gaactattca attagtgttc aaaatgcagc agtggcgtcc 240

gatatagaac aatgttcaaa attaggtgta tctattctgc agcaaggtgg caatgcggcc 300

gattcagcag tcaccgtggc cctgtgtatc ggaacaatca attcgtattc gtccggtata 360

gggggaggag gattcattgt ctctaagtta attgataatc ctaccgctct gagttttgat 420

tgtcgagaaa tggctccttc taaaagtttc aaagaaatgt tcaactatca tgaggagaag 480 Page 38

37324PCT_CRF_sequencelisting 19 Apr 2022

gccagagtag gtggtttggc tgtcgccatt ccaggagagt taaagggact ctatgaactg 540

tttcagcacc atggttctgg taatgttgag tggaaagatt tgattttgcc cgttgctgag 600

ttggctgagg tgggatggac tgtcgatccg ctgttttcta gtgcattgaa atctattgag 660

caccatattt acgagcattc atatgattgg gcctttgcat tgaatgaaga cggaaaaatt 720 2022202534

aaaaaaagag gtgactggat taatcgtccc atgttggcta ctacgttgag gagaatagct 780

gaaagtggca acgttgatct attctatgac ccagagagcg atatagtaca aagcatggtg 840

aatgctacta gaaagtatgg aggaatcctt gaagcctcag actttgcaaa atatagagtt 900

cgaattgaag aatcgttgac attgcataac tttacatctg acggccttac ggtttatacg 960

tccaatgggg catcctcagg gttggtgctc cttgctgggt tgaagctcat ggacttattc 1020

gaagatttca aggaatttca taatgatttc ggggctgttg agtctcaaag gcttgttgaa 1080

acgatgaagt ggatggcttc agtaagaagc aaccttggag atttgaacat ttactccacc 1140

aacgaaactg aaattgacga tcataggaag aggtacgaca gatacaaatc agatgagtgg 1200

gcaatagaaa ctcatgccaa aattaatgat tcccacacac ttccttcttg gaaagattat 1260

gctccagcct ttctacctaa tgatcctcat ggtacatctc atttcagtat cgttgaccaa 1320

tacggtaatg cggtggctat gacaaccact gttaaccttg gatttggatc taaaatacac 1380

gatcctatat cagggattat tctaaatgat gaaatggacg atttttcagt tccaacatca 1440

tctaatgcat ttggtttgca tccatcaatc tataattggg tagagcctta caaaagacct 1500

ctctcttcat gtgctcctac cgtaattgtt gattctctgg gagtacctca ttttgtcatc 1560

ggggcagcag gagggtccaa gatcactacc acagttttac aagcaattat aagagtttac 1620

cattatcacc tggatctttt agacgtcatt gcatatccac gctttcatca tcaactactt 1680

ccggaagaag ttcttctgga gtttccacga gataataaac taatacgcca tctaaaagaa 1740

agagggcatg atgttagagt ccaagcacca atatccacca tgaatggtat cctacgaaaa 1800

agaggtggaa gcctgatagc agttagtgat cactggagaa agcttggtcg accttggggc 1860

ttttga 1866

<210> 32 <211> 1605 Page 39

37324PCT_CRF_sequencelisting 19 Apr 2022

<212> DNA <213> Pichia pastoris

<400> 32 atgaaatcgg ttatttggag ccttctatct ttgctagcat tgtcgcaggc attgactatt 60

ccattgctgg aagagcttca acagcaaaca ttttttagca agaaaaccgt tcctcaacaa 120

gttgctgaat tggtgggcac ccattactct aaggatgaga taatcagtct atggaaggac 180 2022202534

attgagctgg atgtacccag ggaaaagatc caagaggcct tcgataagtt cgtaaaacaa 240

tcaactgcca cttcccccgt tagaaatgaa tttcccttgt ctcagcaaga ttgggtgaca 300

gtgaccaaca ccaagtttga taattatcaa ttgagggtta aaaaatccca ccctgaaaag 360

ctaaacattg ataaggtaaa gcaatcttcg ggatacctgg atatcattga tcaagataag 420

catcttttct attggttttt tgaatcccga aatgatccgt ccacagaccc aatcatccta 480

tggttgaatg gtggacccgg ctgctcttct attacagggt tgctattcga aaagattggc 540

cccagttaca tcaccaaaga gattaagccg gaacataatc cttattcatg gaacaacaat 600

gctagtgtta tcttccttga gcaaccggtt ggagtaggat tttcttactc ttctaagaaa 660

gtcggtgata ctgcaactgc tgccaaagat acatatgtgt ttttggagct tttcttccaa 720

aagtttcctc agttcctgac ctctaatctg cacattgctg gggaatcgta tgctggccat 780

tatttgccca agattgcttc tgagattgtg tctcacgcag acaagacgtt tgacctttca 840

ggagtcatga tcggtaatgg tcttactgat cctctaattc agtataagta ctatcagcca 900

atggcctgtg gaaaaggtgg ctacaagcag gtcatttcgg acgaggaatg tgatgaattg 960

gatagggtct atccaagatg tgaacgttta acgcgggcat gttatgagtt ccaaaattca 1020

gttacttgtg ttccggcaac actttattgc gaccaaaagc tactgaagcc gtacactgac 1080

actggcttga atgtctatga tattcgtaca atgtgcgatg aagggactga tttgtgttac 1140

aaagaactgg aatacgtgga gaagtacatg aaccagcctg aagtgcagga agccgtgggc 1200

tctgaagtca gttcttacaa aggttgtgac gatgatgtct tcttaagatt tttgtactct 1260

ggcgatggat ctaagccttt ccaccagtat atcacggatg ttctcaatgc aagtattccg 1320

gttctgattt acgcaggtga taaagattat atctgtaatt ggctaggaaa ccaagcttgg 1380

gtcaatgagc tagaatggaa cttgtctgag gaattccagg caactccgat tcgaccgtgg 1440

Page 40

37324PCT_CRF_sequencelisting 19 Apr 2022

ttcactttgg acaataacga ttatgcagga aacgtacaaa cttatggaaa cttttccttt 1500

ctaagagtat ttgatgctgg tcacatggtt ccttacaatc aaccagtcaa cgcacttgac 1560

atggttgtca gatggacaca cggtgatttc tcatttggtt attaa 1605

<210> 33 <211> 2520 2022202534

<212> DNA <213> Pichia pastoris

<400> 33 atgactcaat tagatgtcga atcattgatt caagaactca cactaaatga aaaggttcaa 60

cttctgtccg gatcagactt ttggcacacc accccagtta gacgtctagg aattccaaag 120

atgagattat ctgacggtcc taacggcgtc cgaggaacca agtttttcaa tggagttcca 180

accgcatgtt ttccttgtgg tactggatta ggtgccactt tcgataaaga acttctaaaa 240

gaagctggct ccttgatggc agacgaagct aaagcaaaag ctgcctcggt agttttgggt 300

cctacagcta acattgctcg aggccccaac ggaggaagag gcttcgaatc ttttggagag 360

gatccagtgg ttaatggatt atctagtgct gcaatgatta atggattgca aggtaaatat 420

attgcggcta ccatgaaaca ttatgtttgt aacgatttag agatggatcg taattgcatt 480

gatgcacagg tgtctcacag agctctaaga gaagtgtacc ttcttccatt ccaaattgcg 540

gtaagagatg caaatcctcg cgctatcatg actgcttata ataaagcaaa cggtgaacat 600

gtatctcagt caaagtttct tctagatgag gttttgagaa aagaatgggg ctgggatggt 660

ttgttaatgt ccgattggtt cggtgtgtac gatgcaaagt cttctatcac taatggtctt 720

gacctggaaa tgcctggtcc acctcagtgc agagtccatt cggcaaccga tcatgccatc 780

aattctgggg agatacacat aaatgatgtc gatgagcggg tgcgaagcct cttaagttta 840

attaactatt gtcaccagag tggcgtcact gaggaggatc cggagacatc cgataacaac 900

accccagaga ccatcgaaaa actcagaaaa atcagtagag aatcaatcgt cttgctgaag 960

gatgatgaca ggaacagaag tatccttcct ctgaagaagt cagataaaat tgccgtgatt 1020

ggaaacaatg ctaagcaggc tgcatattgc ggaggaggtt ctgcttctgt tctctcgtac 1080

catactacaa ctcctttcga ctctatcaaa tcacgattgg aagattcaaa cactccagct 1140

tacaccatcg gtgctgatgc ttacaagaac cttccgcctt tgggccctca gatgacagac 1200 Page 41

37324PCT_CRF_sequencelisting 19 Apr 2022

agcgatggaa aaccggggtt cgacgccaaa ttttttgttg gctcgcctac atctaaagat 1260

agaaagctga ttgatcactt tcagttgacc aattcacaag tcttcctggt tgactactat 1320

aatgaacaga tccctgaaaa caaagagttt tacgtagacg ttgaagggca attcattcct 1380

gaggaagatg gaacctataa ctttggcttg accgtattcg gaacgggaag attattcgtg 1440 2022202534

gatgataagc tggtttccga tagtagccaa aaccagaccc ctggagattc cttttttgga 1500

ctagcagctc aagaggttat cgggtccatt catttggtca agggtaaagc atataaaata 1560

aaggttcttt atggatccag tgtcaccaga acatatgaaa ttgcagccag tgttgctttt 1620

gaaggaggag catttacttt tggtgcagca aaacaaagaa atgaagatga agaaattgct 1680

agagctgtgg aaattgctaa ggcaaatgat aaagtggtgt tgtgcatagg tctaaatcaa 1740

gactttgaaa gtgagggatt cgacaggccg gatatcaaaa ttcctggagc aaccaacaag 1800

atggtaagtg ctgttttgaa ggctaaccct aacactgtga tcgtcaacca aacaggaacc 1860

ccagtcgaga tgccatgggc cagtgacgct ccagtgatct tgcaggcttg gtttgggggg 1920

tctgaggcag ggaccgctat agctgatgta ctattcggtg actacaaccc tagcggaaaa 1980

ctaacggtta cttttccctt gagatttgag gataaccctg catatctcaa cttccaatcc 2040

aataagcaag catgttggta tggggaagac gtttatgtgg gctacagata ttacgagacc 2100

atagacaggc ctgtgttatt cccatttggc cacggattgt cattcaccga atttgatttt 2160

accgacatgt ttgtcaggct tgaagaagaa aaccttgaag ttgaggttgt agtcagaaac 2220

acaggaaagt atgatggtgc tgaagttgtg cagttgtacg tagcaccagt atccccatcc 2280

ctgaaaaggc ccatcaaaga actcaaggaa tatgctaaga ttttcttagc cagtggtgag 2340

gcaaaaacag ttcacctgag cgttcctatt aagtatgcca cttcgttctt tgacgaatat 2400

cagaagaaat ggtgctccga gaaaggagag tacacaatct tactgggatc cagctcagca 2460

gatattaaag tttcgcaatc tattacttta gaaaaaacaa ctttttggaa aggtttatag 2520

<210> 34 <211> 5004 <212> DNA <213> Pichia pastoris

<400> 34 Page 42

37324PCT_CRF_sequencelisting 19 Apr 2022

atgttcctca aaagtctcct tagttttgcg tctatcctaa cgctttgcaa ggcctgggat 60

ctggaagatg tacaagatgc accaaagatc aaaggtaatg aagtacccgg tcgctatatc 120

attgagtatg aagaagcttc cacttcagca tttgctaccc aactgagagc tgggggatat 180

gactttaaca tccaatacga ctactcaact ggttcccttt tcaacggagc atctgttcaa 240

atcagcaacg ataacaaaac cactttccag gatttgcaaa gtttgcgtgc agtcaaaaat 300 2022202534

gtttacccag ctactctcat tacattagat gaaacatttg agcttgctga cacgaagcca 360

tggaaccctc atggaattac cggtgtcgat tctttgcatg agcaaggata tactggtagt 420

ggtgttgtta ttgcagttat cgatactggt gttgactata cacaccctgc tctgggtggt 480

ggtatcggag ataatttccc tatcaaagct ggttatgatt tgtcttccgg tgatggtgtc 540

atcacgaatg atcctatgga ttgtgacggt catggtacct ttgtatcctc catcattgtt 600

gcaaataaca aagatatggt tggtgttgca ccagatgctc agattgtcat gtacaaagtg 660

ttcccctgtt ctgatagtac ttcgactgac atagttatgg cgggtatgca aaaggcctat 720

gatgatggtc acaagattat ttcgctatca ctgggatctg actcggggtt ttccagtact 780

ccagcttcct taatggccag caggattgct caagacagag ttgttttggt ggctgctggt 840

aactctggag aacttggtcc attctatgcc tcctcccctg cttctgggaa acaagtcatt 900

tcagttggat ctgttcaaaa cgaacaatgg acaacctttc cagtaacctt tacctcttca 960

aacggtgaat caagggtttt tccttacctc gcttacaatg gtgcacagat tggatttgat 1020

gccgagcttg aggttgattt taccgaagaa agaggatgcg tctatgaacc agagatctcc 1080

gcagataatg cgaataaagc tattttgtta agaaggggcg tcggctgtgt tgaaaacttg 1140

gaattcaatt tattgtctgt ggctggttac aaggcttact tcttgtacaa ctcattttca 1200

agaccatgga gtctcttgaa tatttctcca ctgattgagc tagacaacgc ttactctctt 1260

gttgaagagg aagttggaat atgggtgaaa acccaaatcg acgccggtaa caccgtcaag 1320

ttaaaggtga gcacgagtga ccaaatgttg ccatctgata aagagtattt gggagttgga 1380

aagatggatt attactcctc tcaaggacct gcttatgagc ttgaattttt cccaacgata 1440

tccgctccag gtggagacag ttggggcgct tggcccggtg ggcaatacgg tgttgcctca 1500

ggaacaagtt ttgcttgccc ctatgttgca ggtcttacag ctctttatga atcgcagttt 1560

Page 43

37324PCT_CRF_sequencelisting 19 Apr 2022

ggaattcaag atccccagga ctatgtgaga aaattagtct ccacagctac cgatcttcaa 1620

ttatttgact ggaacgcagt gaaacttgag acctctatga atgctccact tattcaacag 1680

ggagctggtc tagtgaacgc tcttggtttg tttgagacta agactgtgat cgtgtctgct 1740

ccttatttgg agctcaatga caccatcaat agagccagtg agtataccat tcaaattaag 1800

aatgagaact ctgagactat tacctatcaa gttgttcacg ttccgggaac tactgtctac 1860 2022202534

tctagatcag cttctgggaa catcccatac ctggtcaatc aagattttgc accttacggt 1920

gatagtgatg ctgcgacagt tgctctatcc acagaagagt tggttttggg accaggagaa 1980

gttggtgaag tcactgtgat cttctctaca gaagaaattg atcaagaaac tgctccaatt 2040

attcagggta agattacatt ttatggtgat gtcataccga ttgctgttcc ttatatggga 2100

gttgaagttg atattcattc ctgggagcct ctcattgaga ggcctttatc agtgagaatg 2160

tatttggatg atggttcctt agcatatgtt gatgatgatc ctgattatga gttcaatgtg 2220

tatgactggg attctcctag attttatttt aacctgagat atgcaaccaa agaagtatcg 2280

attgacttgg tgcaccctga ttatagcatt gagaacgact acgaatggcc tttagtttcc 2340

ggacacaaca actattatgg tcccgtggga tacgactacg attatacctc gggtcaagcc 2400

tttttgcctc gttactttca acaacgtatt aacgaacttg gatatctttc tttttccaga 2460

tttgctaact tttctgtagt tcctgctggt gaatacaaag ctctatttag agttttgcta 2520

ccatatggag acttttggaa caaagaagac tggcaattgt ttgaatcccc agtgtttaac 2580

gtcctcgctc caccgaatga agaaaacact actgaagagc caactgagga atccagcgag 2640

gagcctaccg aagagtcaac gtctgagtca actgaagagc cctcttctga gtcaactgag 2700

aaatctagcg aggtgccaac tgaagaaatt actgaagatg caacatccac aattgatgat 2760

gatgaagcat ccaccgaaag ctctactgaa gaaccaagtg ctcagcccac cggtccttac 2820

tctgatttga ctgtcggtga ggccattacc gacgttagtg tcaccagttt gaggacaact 2880

gaagcatttg gatacacttc cgactggttg gttgtgtctt tcactttcaa cactactgac 2940

agagatatta ctctcccacc ttacgctgtt gtacaagtaa ctatcccaaa tgaacttcaa 3000

ttcattgctc atccagaata cgccccatac cttgagccct cattgcaagt tttctacact 3060

aagaatgaaa gattaattat gactagtcag ttcaactacg acaccagagt catcgacttc 3120

Page 44

37324PCT_CRF_sequencelisting 19 Apr 2022

aagtttgaca atcgagacca agtaataact caagtggagg gagttgttta tttcacgatg 3180

aaactagaac aagatttcat ttctgcattg gccccaggtg aatacgattt tgaatttcat 3240

acatccgttg attcttatgc ttcgaccttt gactttattc cattgattag atccgagcca 3300

atcaaattga tagcaggtgc accagacgaa gttgaatggt ttattgatat tccaagtgca 3360

tacagcgatt tggcaacgat agatattagt tctgatatcg atactaatga taatttgcag 3420 2022202534

cagtacttct atgattgctc aaagctcaag tacactattg gaaaagagtt tgatcagtgg 3480

ggtaatttta cagctggatc agatggtaac caatacagca ataccaccga tgggtatgtt 3540

ccaattactg attctaccgg ctctccagta gctgaagttc aatgtttaat ggaaagtatc 3600

tcattgagtt tcacaaatac tcttgctgag gatgaagtat tgagagttgt tcttcactct 3660

tctgcgttta gacgtggttc attcaccatg gccaacgtgg taaacgttga cattacagct 3720

ggtggattgg caaaaagaga actcttctct tatatattgg atgaaaatta ctatgctagt 3780

actggatctg aggggttggc atttgacgta tttgaagttg ctgatcaggt cgaggagcca 3840

actgaggagt caacctcaga ggaatctact gaacaggaaa cttccaccga ggaacctacc 3900

gaggaatcaa ctgaacctac tgaggaatct acccaggaac ctactgaaga gcccaccgac 3960

gagcctactt ctgagtcaac tgaggaacct tctgaggagc caacttctga cgatctctca 4020

attgacccaa ctgctgtacc taccgatgaa cctactgaag agccaactga ggagcctact 4080

tctgagtcaa ctgaggaacc ttctgaggag ccaacttctg acgatctctc aattgaccca 4140

actgctgtac ctaccgatga acctactgaa gagccaactg aggagccgac ctctgagact 4200

accgatgatc catcgatagc acctactgct gtgccaactt ccgacacatc ttctggacaa 4260

tcggtggtta ctcaaaacac tacagtcact cagactacca tcacttcagt ctgtaatgtt 4320

tgtgctgaga cccctgtaac aatcacttac actgcaccag ttgtgactaa gccagtttct 4380

tacaccaccg ttacttcagt ttgccatgta tgtgcagaga caccaatcac agttaccttg 4440

acgttgccat gtgaaaccga agacgtgaca aagactgccg gccctaagac tgtcacttac 4500

accgaagttt gcaactcctg tgctgacaag cctatcactt acacctacat cgctccagag 4560

tacactcaag gtgccgaacg tacaacagtt acatcggttt gcaacgtttg tgctgagaca 4620

cctgtaacgc taacatacac tgcgccgaaa gccagtcgtc atacagttcc ttcacaatat 4680

Page 45

37324PCT_CRF_sequencelisting 19 Apr 2022

tcaagtgccg gagagctcat ttcatccaag gggatcacga ttcctactgt tcctgcccgt 4740

ccaactggta cttatagtaa gtctgttgac actagccaac gtacactcgc taccattaca 4800

aaatcttcag atgagtctaa cactgttacc actactcaag ccacacaagt tttgagcggt 4860

gaatccagtg gaattcaagc tgcttcaaac agcacgagca tctcagctcc aactgtcact 4920

acagctggga acgagaactc tggatctaga ttttcgtttg ctggactatt cacagttctg 4980 2022202534

cctcttatct tgttcgttat ataa 5004

<210> 35 <211> 1335 <212> DNA <213> Pichia pastoris

<400> 35 atgcagtttg cttccttact gcttctcttg tatattttct tggggcaaat ttatcctact 60

gaagcagcaa aatattttgt tcgtctgaag aagcctcaca cactagacct cttgttcaaa 120

caggatgaag cagatgcatc tgctgagaac cgaatctctc ttcatggttt aagggaccga 180

atcaaaaaaa agatctcttt tggaacgttc gaaggttttg ttggtgaatt cacaacagaa 240

cttgtagaaa aactaaaaaa gaattcgttg attgcagaca taactcctga cattatcgtc 300

tcatcttgcg atatcgaatt gcagtccccc gctcctgatc acctggctag gttatccaaa 360

gaaggtgccg taagagcaca agatcgtctt cttggaccgg aatttttcta cgatggtgac 420

tggactggag aaggcgtcaa tgtatacgtg atagacacgg gtatcagggt aaatctagat 480

gaatttgagg gcagagcatc atttggtgct gattttacag gcactgggaa agatgactct 540

gttggtcatg gaacccacgt agctggtctt attggctcca aaacttttgg agtggccaaa 600

aatatcaact tgatatccgt aaaagctctc tctggtaatg ggagcggttc gctttcagag 660

gtcctacagg cgattgaatt cgcagtcaag catatgaaag ccagtcgtaa gccaggtgtt 720

gctaacttgt ctctaggtgc accaaaaaat tcaatccttg aaaaagcgat tgaagaggca 780

ttcaagaacg gtttagtcat agtagcagca gctggcaatg ccttcgtgga tgcctgtaac 840

acatcccctg caaactctcc atatgcaatc accgttggag ctataggtga tcacaacgat 900

gaaataacta gattttccaa ctggggagcc tgtgtcgatc tttttgcagg aggggacaca 960

attgtaagtg taggacttct caatggagtc gctgtccgca tgtctggaac ttcgatgtct 1020 Page 46

37324PCT_CRF_sequencelisting 19 Apr 2022

gctccaatag tcgcaggctt agccggaata ttacttgacc agggtgtggc cccagaagat 1080

gtaaaaggta agttaataga gctctcagat gaagggaaga tcaacgataa tactggaatt 1140

ctaaagccgg gaactccaaa ccgaatagcc aacaatggaa ttcgaaaaag tgattatgaa 1200

gatcaaaaag aaaatgacaa tgatgaagac gatgaagacg gggaagacaa tctagaagac 1260 2022202534

attgaagagg acgaggatta ttgggatgaa gagagaaggt atagggaata tgcggtatct 1320

agtttagtct tctaa 1335

<210> 36 <211> 546 <212> DNA <213> Pichia pastoris

<400> 36 atgttcaaca ttatccaacg gatacagagt ttgagcaatt tttatttaac ggtttccatt 60

ctattatgta ttgttacaac agttgtctca attattagta tgttcttgga tgaaacgtcc 120

agtattcctg cccaattaag caatgttgta atatcaacaa atttaaagta tagcagatcg 180

tttggttcag tcggtggtag acctaaagaa aactccaaga ttttatttga tcttgatatg 240

gatctggctc cattattcaa ttggaatact aaacaactgt ttgtacaatt ggtagcagag 300

taccctacct ctgttgccga tgatggtgcg aaggtgacct attgggatag cataattact 360

gagaaaaagt acgcaagagt gcatgtcaat aagcagaggg gaaaatactc agtttgggac 420

gtgtcggact cctttcaagg ccgcaatgct acggttaaac tgaaatggaa cttacagccc 480

tatgtcggct ttctattctt tggacaaact aagggagaga ttgaggtggc ctatcctgca 540

acataa 546

<210> 37 <211> 870 <212> DNA <213> Pichia pastoris

<400> 37 atgagtgtca tagtgcatcc tcttgcacta ttgacaataa tcgacgagtt ccagagacga 60

ggtcgcaaca acgattccat aatattcggt gggttacttg gtaaacatga tgaatccacc 120

aaccaaatat ctgttgttaa cagctttgtg ataccattga tcgataatca gtttttgaat 180 Page 47

37324PCT_CRF_sequencelisting 19 Apr 2022

aaagagtact tgcaggacat gctactcaaa ttttctatca ttaattccaa ctttcgattc 240

gtaggttact atcacgttca atctttaaac ggtaccgaaa ctcaacagta tgacttgaac 300

gctattaacc tagtatgcca agatgataat aggccttcgt cctttgtcca ttggatagta 360

acagatccaa aagagttcaa atcattctcg atgtattact tggatgattc aatggttcaa 420 2022202534

ctcgtcaatt ccaatattca acattacatt tctaaaccat tgccctatga atttaaaaac 480

cttctgtctg agaaaattgc tatcgacaca atcctcaagc aatccaggct agaaaaagac 540

ttatccacca aaaactcact gaagaaatta aacaatagtt atatcgacat tcattcctca 600

ctgaacgttc tctataaatc agtcaatagg cttattcgtt acctcaaaaa atgctcaaaa 660

tcagaagttt caattgacta tgacacagtt caggaaatga atactgtaat actgaaaatt 720

gaaaggctta aattgatacc ccaagtcaag gaggagtttg acttagtgac tctttcacta 780

ctggtagaca atcttgatca gatggatcat cttttgtatc tccggaaaca agtggaacag 840

tacaaaatat ctgaatcaat gtatagttag 870

<210> 38 <211> 1167 <212> DNA <213> Pichia pastoris

<400> 38 atgaaatttc actcgattgt cttcacattt tcactcgttt tgagttcact ggcgttgtcg 60

ataccatggg tgtctgacca catggtccag catctttttg ccgacccttc aatcagtaaa 120

ggtcctgatg tagatctcgt tgggctacat aagcatttgg tcagcatcaa atctctttcg 180

ggctatgaac aagaagtagt atcgtggttg gccgattatc tagccagtag gggtcttact 240

gtggagttga acaaggtcga ggacgaaact gaacgttaca atttgtatgc ttatttggga 300

accacccgca acactaaggt tgtgctaact tctcacttag acacagttcc cccttatctt 360

ccctacaaag ttgaggaagg tggctatatc tttggcagag gaagctgtga tgctaaggga 420

tcagttgcgg cacaagtgat tgccttccta aatctcttgg aagagggctc catcaaagaa 480

ggtgatgtca gtcttttgta cgtcgttggt gaagagattg gaggtgatgg aatgcgcaca 540

gctagcaaga ccttgggtgc taaatgggac actgccattt ttggagaacc taccgagaac 600

Page 48

37324PCT_CRF_sequencelisting 19 Apr 2022

aagcttgcca ttggacacaa gggaattgca ctgtttgacc tgaagattac aggaaaatcc 660

tgtcattctg gataccctga gctgggaatt gatgccgacg ctatgttggt ccagattttg 720

cacaagttgc tttttgagac ttcttggcct gtcagtgatt tgctgggaaa ctccacagtc 780

aacgcgggac agatcaacgg aggagtagct gctaatgtta tttcttcgga agcacatgcc 840

aaggttttaa tccgcgtggc taaagacatt gacgctgtag agaagctgat ctacgaggcc 900 2022202534

attgccccct tcgaggagta tacagacatt acctttcact ccaaagaaga tgctactttc 960

ttggattaca aggttgaagg gttcgagaac tacattgcag cctacagtac cgatgtacca 1020

ttcctagtga cgggctccaa tttgaccaga tatttgtacg gaccaggaag catcatggtg 1080

gctcatgggc ctgatgaaat ggtcaaggtt tcagacctgc aggatagtgt tgacggatac 1140

aagcgattag tctccgtctc actttag 1167

<210> 39 <211> 1776 <212> DNA <213> Pichia pastoris

<400> 39 atgccagaga aaaagaaaca aaaaaaagag tcgacatctc cattcaaggg taacctagtt 60

gggatctcat tggtagctgt ggcattgttt gccatctacc agtacctcta cccaagctcg 120

ttttcctctc agcctgaaac cccagcccca gttttcgatc tgagcagtga attagaagca 180

ttgtgtcccg tgtaccctgc agtcagatct tccgacttcg aaaaggatcg ccccatctta 240

gagagaattc tgaacgatcc ctcatttaga atcgcttctg ctcaaaaact gagtaaggct 300

gttcagatcg atacccaagt gttcgacgaa caattggacg tggctcaaga ccctgaagtt 360

tggaccaaat tcgtcaagtt ccatgaatat ttggaggcaa ctttccccac cgtttactcc 420

caattgaagg tcgacaaaat caacacctat ggcttggttt tcacttggga aggctcagac 480

cctagtctga aaccactcat gttcttggct caccaagacg tggttccagt ccagaaagat 540

actcttcagg attggtcata tccccctttc gaaggacgta tcgccgatga cagagtttgg 600

ggacgtggat cagctgattg caagagttta ctgattgcat tactggaaac cgtagaattg 660

ctggtagatg aagggtactc accaaagaga ggtgtcatcc tcgcatttgg attcgacgaa 720

gaagcttcag gtacctacgg tgctcacaat atctccaagt ttttgcttga gaaatatggg 780 Page 49

37324PCT_CRF_sequencelisting 19 Apr 2022

ccagatagta ttgccctcat tttggatgaa ggtgaggctg tcagttacgt ggacaagaaa 840

caaactaccc tcgttgcaaa gattgctacg caggaaaagg gttaccttga cctagaggtc 900

gcattgacca ctgtaggagg ccattcttct gtccccccta agcacactgc aattggcctt 960

atttccaagt tggtcacaca tatcgaagat catccattgg acccagaaat tagtaccaga 1020 2022202534

aatcctctgg tacagttttc gaactgtctt ggtgcagctg gggctttgag agatgacttc 1080

aagactgctc ttgttgcata cagcaaggat ccgtcgaaca acattgtcaa acaaggtgtg 1140

attaaaggta tttccaagat tgcatttttc ttcggttctt tgattaccac aacacaagcc 1200

accgatctta ttttcggtgg agagaagatc aatgctttgc ctgaaagtgc tagagtagtt 1260

atcaaccata gagtggacgt tgagcgtgat tcagcccaaa tcatagacag attgattcac 1320

ttccacgttg ttcctattgc caaggagcac ggtttcaagg tcacttacag tgactatggt 1380

agtgacaaag ttgaaactgt ctacgagcca gaaggagttg cctcattggg agaattccac 1440

gtttctcctt tctccagagt ctgggagcct gctccagaat ctccatccga cgacaatgtc 1500

tggtccatca tttctggtac cactcgtacg atatttgagg agtttgtgga cccctcggct 1560

aaacttattg caagtccata catgatgcct ggtaacaccg acactcgaca ctactggccg 1620

ctgacaaaga atatctatag atacgttcca ggtattgtag atatttacaa ggctaagata 1680

cactcggtag atgaatctac cgaggttgat gcccacttgc aagttatagc tttctaccac 1740

gagttcatca aggttgccag cgaatgggag ctttga 1776

<210> 40 <211> 1275 <212> DNA <213> Pichia pastoris

<400> 40 atgaaatcct ctaaagaact atacaaggag gctctcaact atgaatactc ttccgcggtt 60

tctttcaagg cctgggttcg aagtgctcaa atcattttgc gacatgcccg gcagtttgct 120

gaacaaagat acatcagtga gtgctataag ttgtctgttc gttttgtaga cttgattgtg 180

aacaagatgg ccacgcataa agagctcaag caattgaaga aaataaatgc accagtatat 240

ctcacctatt tggatttggc tacgaagaaa gtcccagatg tcatcaagga atgtgaggcc 300

Page 50

37324PCT_CRF_sequencelisting 19 Apr 2022

ttgaagacaa ttttggatga tgagtaccaa agctacctca aactgcaaca attgaaacga 360

cagaagcaga aagaccaatt gatccatcat cagaatcagg ctcaaacgca taaattacgt 420

agatcttcat caatattgaa agatcatatc aacgctgttg atgaaagagc gctgttgaaa 480

caactacagc agttgacata ccatgatcgt gaattcgcaa ccgcaataac ggagatgcca 540

aattatccag agatccccca gctgagtatt tcaacgaatc agaacactag atcagaggca 600 2022202534

cccccacttc caccaagagt atcgcaggaa cagtcattag caccagtatc actagattca 660

tcacaggcag atttacaaca caaaactgtt aacttcaccg aagctgggca accattacga 720

acagtattta tttcagatag actccaatct gagttcctta gactagcgga accaaacacg 780

atacaaaagc tagagacttg tggcatcctt tgtggaaagc tcgtcagaaa tgcattcttc 840

atcacccatt tggttatacc agatcaagag tcgacaccaa acacatgtaa tacaagaaat 900

gaggaaaagt tattcgacac tatagatcag cttgatttat ttgtccttgg atggatacat 960

acccacccaa cacaatcatg cttcctgtct tccatagact tacatacaca gaattcgtac 1020

cagatcatgt taagcgaagc aattgccatt gtgtgtgcac cagcacctca gttttctcat 1080

cattcttttg gatgttttcg gctaacccat cctccgggaa ttccaaccat tacacaatgc 1140

actaggacgg gatttcatcc tcatgaggaa cccaatctgt atgtgacttg taatcgaaag 1200

aacatgggcg acgtgcaagg cggacacgtt gtgatcaaga atcatttacc gtttgaaaag 1260

cttgatctaa gataa 1275

<210> 41 <211> 1347 <212> DNA <213> Pichia pastoris

<400> 41 atgactagtt ctgtagataa agtgagtcag aaggtcgctg acgtaaaact gggctcctcc 60

aagtcaacaa agaataacaa gagcaaaggt aaaggaaaat ccaacaagaa tcaagtggtt 120

gaggatgatg atgaggatga ttttgaaaag gccttggagc ttgcaatgca attagatgca 180

caaaaactag ctcagaaaaa agctgatgat gtgcctcttg ttgaagaaga agagaaaaaa 240

gttgaggaaa agattgaaca gcaatatgac cccatttcca ctttttaccc tgatggaaac 300

tatccccaag gagaagttgt ggattacaaa gatgacaact tgtaccgtac tactgatgaa 360 Page 51

37324PCT_CRF_sequencelisting 19 Apr 2022

gaaaagcgag ctttggatcg agagaagaat aacaagtgga atgaatttcg taaaggtgct 420

gaaattcata ggagagttcg aaaactggca aaggatgaga tcaaaccggg aatgtcaatg 480

atcgagatcg ccgaactaat cgaaaacgca gttcgtggat atagtggtga agacggactc 540

aagggtggta tgggatttcc ttgtggtctt tctttgaacc attgtgctgc gcactattct 600 2022202534

cctaatgcta acgacaaact tgtcttaaat tatgaagacg tcatgaaagt agattttggt 660

gtccatgtga acggtcacat tatcgatagt gcattcacgt taacattcga tgacaaatat 720

gatgatctgt tgaaagctgt caaggatgct accaatactg gtattcgtga agcaggtatt 780

gatgtgagat tgaccgacat tggtgaagcc atccaagaag taatggagtc ctacgaagtt 840

actttagacg gagaaacata ccaagttaaa cctatcaaga atctttgtgg ccataacatc 900

ggccagtata gaattcatgg tggtaagtct gttcccatag tgaagaattt tgacaacacc 960

aagatggagg aaggtgaaac ctttgcaatt gaaacctttg gcagtacagg aaggggtcat 1020

gtgataggac aaggtgaatg ctctcactac gccaagaatc cagatgcccc cgccaatgct 1080

atctccagca ttcgtgtgaa ccgtgctaaa caattgctaa agactatcga tgagaacttt 1140

ggtactcttc cattctgtcg tcgctacata gatcgtcttg gagaagaaaa gtacttattg 1200

gcattgaacc agttggttaa atctggagtt gttagcgatt atccaccctt ggtagatgtc 1260

aaggggtcat acactgccca atacgagcac accatccttt tgagacctaa tgttaaggaa 1320

gttgtatccc gcggtgaaga ctactag 1347

<210> 42 <211> 1119 <212> DNA <213> Pichia pastoris

<400> 42 atgattcaca gctgtgctag tgctgagtgc tcaaaagcga ctgaatctac cttaaaatgt 60

cccttgtgtc taaaacaagg tcagatccaa tatttttgta accaaaaatg tttcaagaat 120

ggatggaaga tccacaaagc ggttcacgcc aaagatggtg atatagatgg ttcgtacaac 180

ccctttccca actttgccta caccggtgag ctcagaccag catatccctt gtctgtgaga 240

cgagaggttc cagagaacat tactctccca gattatgctc ttgatggagt accagtctca 300

Page 52

37324PCT_CRF_sequencelisting 19 Apr 2022

gaaatcaaaa ataacagaat gaacaagatc aatttggtaa cggagccaga agacctggcc 360

aagctaaaaa atgtttgccg tttagcacga gaggttctag atgctgcggc tgcatctatc 420

aaaccaggag ttaccactga tgagatagat gaaatcgttc atagtgaaac aatcaagaga 480

gaagcatacc cctccccttt aaattacttc aattttccca aatctgtttg cacatccgtt 540

aatgaagtca tctgccacgg tatacctgat cgtagaccgc tccaggatgg tgacatcgtg 600 2022202534

aacctggatg ttacccttta taaagatgga tttcatgcag atctgaatga aacgtactat 660

gttggagaga aggccaagac taacaaagat ctggtcaacc tcgtcgagac aaccagagaa 720

gctcttgctg aagctatccg tttagtgaaa cccggcatgc cgttccgtca aattggtact 780

gttatcgaaa actatgtgac tgaaagaggc tgtgaaactg ttcgttctta cactggtcat 840

ggtatcaata ctttgttcca cactgaacca accattccgc attacgctcg taacaaagct 900

gttggagtag ccaaaccagg agtggtattc actatcgaac caatgttgac tctgggcact 960

catcgtgacg tggtttggcc cgacaactgg accgccgtta ccgctgatgg aggaccaagt 1020

gcccaatttg aacataccct tttggttacg gaagatggtg tggagattct cactggcaga 1080

acggaaactt cgccaggcgg tgccatctca agactataa 1119

<210> 43 <211> 1605 <212> DNA <213> Pichia pastoris

<400> 43 atgctctata agaccacctt gtcaatagca cacacgagtg tgatattgtt gtcattgata 60

accgccataa gttgctttga gttgcatctt cctcagaagg tttctcatat agtagacagt 120

ttacaatata cttgcggcca atttttgcaa aagcagcaga tctttgcact ctataacaag 180

caaaatttca ccgaaatagt gaaccagaat atcaagggaa tagaggagag agttttgtct 240

gagttgcttg aagaaagatt agagaatgaa tcccagaatg attattatac cgccaattct 300

caaaattggc ctatcgactt ggatcagtac tcagaatcat ttgtaataag gatcacatct 360

gaagatgagt ttatcaagta cttgatcttc aaggaagcta aagctttgca tatttccata 420

tgggagcaat ctgttggttt gatagatttg aaggttgacc gtgatcagat gcaccgccta 480

ctttacaacg tggagtcacg catactggaa cgaagaacga gaagtgttga cagtccagtt 540 Page 53

37324PCT_CRF_sequencelisting 19 Apr 2022

tctgaatata aagtacaatt gatgattgga gatcttccac agcgaatcta cgaaacatat 600

ccttcgacaa aagtgacatc tttgcaagcc ctaggagagt tcccttcttt ccagaaccta 660

agtaatgctt tttttgagga ttttagaacg ctggaaacta tatacgactg gttcgaagaa 720

atacagaagg aatttcctaa gctagtgtcg atcaactgga ttgggcaaac ttatgaaggt 780 2022202534

cgtgatctga aggctcttca cgttagaggg aagcactctg gcaacaaaac agtagtcgtt 840

acaggtggaa tgcatgcgcg tgaatggata tcagtaacca gtgcatgcta tgccgttcac 900

aaactgctcc aaaactatgc tgacggacac cacaaggaag cgaaatacct ggacaagttg 960

gactttttgt ttgttccagt tttgaatcct gatggatacg aatatagctt taacgaagac 1020

aggttgtgga ggaagaacag acaagaaact tatatgcccc gatgttttgg tatagacatt 1080

gaccattcat ttgattatca tttcgtgaaa tcagaagact taccctgtgg agaggaatat 1140

tcgggtgagt cccctttcga aagtatagaa agtgaagtgt ggaataattt cctgaacaga 1200

accaaagaag aacataagat ctacggctat atcgacttac actcgtattc gcaaacggtg 1260

ctgtatccct atgcgtactc atgcgaaatc ttaccaaggg acgaggaaaa cctgattgag 1320

ctaggttacg gtattgcaag ggccataaga aagagtacag ggaaaaaata tcaagtgttg 1380

aaggcatgcg aagacaggga tgcagatcta ttgcctgatt tgggaggagg aaccgcttta 1440

gattatatgt accacaaccg tgcatactgg gcgtttcaga tcaaattgag ggattccggt 1500

aatcatggct ttctccttcc caaaaagttt atatacccag ttggaacaga ggtttatgcc 1560

tcaattcagt acttttgttc ttttgtgctg aatttagaag gctaa 1605

<210> 44 <211> 1191 <212> DNA <213> Pichia pastoris

<400> 44 atgaaattga ccataacatt agcccataac gatcaaatct tggacattga tgtgtccagt 60

gaaatgctac tatctgacct caaagtcctg ttggagttgg aaacttccgt acttaaaaac 120

gaccaacaat tattttacaa taacaacctg ctcactggag atgactcgcc actggaagat 180

ttaggactca aagataatga actcataatt ctgagcaaag tcgaagcaca tagtgatgtc 240

Page 54

37324PCT_CRF_sequencelisting 19 Apr 2022

aattcacact tgaactctgt tagagaacag ttgatacaaa acccgctata ccaggccagt 300

ttacctccaa gtcttagaga taagctcgac gaccctcaag gcttcaaaga agaagtggaa 360

aaactaatcc aattggggca gtttggacaa tacgggcctt cccgtacttc cgtccaacag 420

gaattagaca gactacaaag agatcctgac aatccacaaa atcagaaacg aattatggag 480

ctcattaacg aacaagctat agaggaaaat atgaatactg cttttgaaat ctcacctgaa 540 2022202534

tctttcgttt ccgtgaatat gctctatata aatgtggaaa ttaatggtgt ccattgtaaa 600

gcattcgtcg atagtggagc ccaaacgacc ataatgtccc ctaaactcgc agagaaatgc 660

aaccttgcga atctaattga taaaaggttc cgaggagtcg cacagggtgt aggaagttct 720

gaaatcattg gtcgtatcca ttctgctccc ataaaaatcg aagatattat tgttccctgc 780

tcattcactg ttttggatac caaggttgac cttctattcg gacttgatat gttgagaaga 840

catcagtgtg tgattgacct taagaacaac tgtttacaaa ttgcagacag aaagacagaa 900

tttttaggag aagcagacat cccaaaggaa ttctttaacc aaccaatgga agctccatcc 960

acagctcctg tcccaaaacc tgtacaacct cctcaacaac tcggtcagcg gccggctgga 1020

agccctccct ccacaattca aagaccagca gtacaaccgc cacctgtgga tatacctcca 1080

gaaaaaatcc agcagttgat caaccttgga ttcggagaag aggagtcgaa agaagcactt 1140

attagatcta gaggaaatgt ggaagttgca gcggctttgt tattcaacta g 1191

<210> 45 <211> 1553 <212> DNA <213> Pichia pastoris

<400> 45 atgccaaacc ttccttctag cttgaacaag atgactgctc aagccgtgaa atacgcaaac 60

ggtatgtcat ctgccctctc ccgtgtttga gactctatcc actaacttta gattttatca 120

ccttcctgaa caattcacct actccatacc atgctgtcga ctccgtaaag tccaaattgg 180

tagagtcggg gtttaacgag ctcagtgaga gagttaattg ggccggaaaa gtcaagaaga 240

atggcgctta ctttgtgact cgtaacaatt cgtccattat agccttcact gttggcgggc 300

actggcagcc aggtaacgga gtgtcaattg ttggagccca tactgattcc ccaaccttga 360

gaatcaaacc catatcccat tcgactaagg agggatttaa ccaagttgga attgaaactt 420 Page 55

37324PCT_CRF_sequencelisting 19 Apr 2022

atggtggagg cttgtggcat acgtggtttg acagagattt aggagtagct ggacgagtgt 480

ttattgaaga agaagaatct ggtaacattg tgtccaagtt agtcaagatc gataaaccag 540

tattgagaat ccccacacta gccatacacc ttaccaaaga gagagctaag tttgagttta 600

ataaggaaac tcaattccat ccaatctcat cgcttgaaaa ctcctctgaa aaggagaaaa 660 2022202534

acaaagatga ggaacatgac gcttgtgcag gagaagattt gactacggag gagtttaagt 720

caattcaatc tgttgtggag agacacaaca aacaattgct tgatctggtg gctgcagatc 780

ttgattgctc tatatcccag atagtggact ttgaattgat tcttttcgac cacaacaaac 840

cagtactcgg aggtttgaat gaagaatttg tgttctcagg aagattggac aacctaactt 900

cttgtttctg tgccactgaa gcgcttataa atgccagtaa agataccaac aggttagatc 960

tggatactaa tattcaactg atctctctgt ttgaccacga agagattgga tcagtttctg 1020

ctcaaggagc tgattcttca tttctacctg acatacttca gcgtataaca agactaactg 1080

gtaatgaggt tagcaccgat ctggaaggac aaccaaattc tttcttttta gagtcaatgg 1140

ccaaatcttt cctactatct tcagatatgg cacatggtgt gcatcccaac tatggggaag 1200

tctatgagaa gctaaatagg ccaagaatca acgagggacc agtgatcaaa ataaacgcta 1260

atcaaaggta cagcaccaat tccccaggta ttgttttgct caagaagatt ggtgagttgg 1320

gaaaggtccc cttgcaattg tttgttgtta gaaacgactc tccctgtggg tcaacaattg 1380

gtccaatgtt gagtgctaaa cttggacttc gaacgctgga cctcgggaac ccccagctct 1440

ccatgcattc tatcagagaa actggaggtg ctcgtgacgt taaaaagttg gtcgatcttt 1500

tcgaaagcta ttttgagaat tattacacct tggagcctaa gattaaggta taa 1553

<210> 46 <211> 1413 <212> DNA <213> Pichia pastoris

<400> 46 atgaacaaag gtccgaaaga attggagggc cgcaagtatc cagcaagagc ccatgcactg 60

acggtcaaaa atcactttat ccaaaagaag gctgacattt caagtcgttc tgcaatcttt 120

attagtggcg aagatctcaa gttgtatcct tactgtgacc aaacagctcc tctcagacag 180

Page 56

37324PCT_CRF_sequencelisting 19 Apr 2022

aatcgttatt tcttttatct gtcaggttgt aatatccctg gatcccatgt cctttttgac 240

ttggacgccg aattgttaat tctggtgcta ccagaaattg attgggatga tgtcatgtgg 300

agtgggatgc ctctttcgat tgaagatgcc tacaagacgt ttgatgtgga caaggtggta 360

tatcttaaag atttgcaagg ctttttgtcg tcgtttggaa aaatatatac aactgacatc 420

aatgatgaaa attctaagtt tggcaatcta ctaacagaga aagatcctga cttgttctgg 480 2022202534

gctctggatg aatccagatt gatcaaagac gactatgaac tcactctaat gagacatgcg 540

tcaaaaattt ctgacaattc ccattacgct gtcatgtcgg ctcttccaat tgaaactgac 600

gaaggccata ttcacgctga gtttgtttat cattcgttaa gacagggatc taaatttcaa 660

agttatgacc cgatttgttg cagtggacca aactgtagta cccttcatta tgttaagaat 720

gacgattcta tggagaataa acacaccgtt ctaatcgatg ctggtgcaga atggaacaac 780

tatgctagtg acgttacaag atgttttccc atcaatggag attggacgaa agagcatctt 840

gagatctata atgctgtttt ggatatgcag gaccaagtta tgaagaagat taagcctgaa 900

gcccattggg atgagctaca ccttttggca catcgtgttc tcattaagca ttttttgagc 960

ctcggcatat ttcataacgg aacagaggat gagatatttg agagtggagt ctcagtatca 1020

ttctttcctc atgggctggg tcacctttta ggaatggata ctcatgatgt tggtgggcac 1080

cccaactatg atgatccaaa ccctctattg agatacctaa gattgagaag agtgttgaaa 1140

gaaaatatgg tagttacgaa cgaacctgga atctacttct ctccctatct tgttgaattg 1200

ggactgaagg atgataataa ggcaaaatat gtcaacaagg atgtactgga aaagtattgg 1260

tatgtcggag gtgtgagaat tgaagacgat attcttgtta cgaaagatgg gtatgaaaac 1320

ttcaccaaga ttactagcga ccccgaagaa atttccaaaa tcgttaaaaa ggggttggag 1380

aagggtaaag acgggttcca taatgttgta tga 1413

<210> 47 <211> 2612 <212> DNA <213> Pichia pastoris

<400> 47 atgacatctc ggacagctga gaacccgttc gatatagagc ttcaagagaa tctaagtcca 60

cgttcttcca attcgtccat attggaaaac attaatgagt atgctagaag acatcgcaat 120 Page 57

37324PCT_CRF_sequencelisting 19 Apr 2022

gattcgcttt cccaagaatg tgataatgaa gatgagaacg aaaatctcaa ttatactgat 180

aacttggcca agttttcaaa gtctggagta tcaagaaaga gctgtatgct aatatttggt 240

atttgctttg ttatctggct gtttctcttt gaccttgtat gcgagggaca atcgattttc 300

caatttgaac gagtacgttc cagattcaaa cagccacgga actgcttctg ccaccacgtc 360 2022202534

taatcgttga accaaaacag actgaattac ctgaaagcaa agattctaac actgattatc 420

aaaaaggagc taaattgagc cttagcggct ggagatcagg tctgtacaat gtctatccaa 480

aactgatctc tcgtggtgaa gatgacatat actatgaaca cagttttcat cgtatagatg 540

aaaagaggat tacagactct caacacggtc gaactgtatt taactatgag aaaattgaag 600

taaatggaat cacgtataca gtgtcatttg tcaccatttc tccttacgat tctgccaaat 660

tcttagtcgc atgcgactat gaaaaacact ggagacattc tacgtttgca aaatatttca 720

tatatgataa ggaaagcgac caagaggata gctttgtacc tgtctacgat gacaaggcat 780

tgagcttcgt tgaatggtcg ccctcaggtg atcatgtagt attcgttttt gaaaacaatg 840

tatacctcaa acaactctca actttagagg ttaagcaggt aacttttgat ggtgatgaga 900

gtatttacaa tggtaagcct gactggatct atgaagagga agttttaagt agcgacagag 960

ccatatggtg gaatgacgat ggatcgtact ttacgttctt gagacttgat gacagcaatg 1020

tcccaacctt caacttgcag catttttttg aagaaacagg ctctgtgtcg aaatatccgg 1080

tcattgatcg attgaaatat ccaaaaccag gatttgacaa ccccctggtt tctttgttta 1140

gttacaacgt tgccaagcaa aagttagaaa agctaaatat tggagcagca gtttctttgg 1200

gagaagactt cgtgctttac agtttaaaat ggatagacaa ttcttttttc ttgtcgaagt 1260

tcacagaccg cacttcgaaa aaaatggaag ttactctagt ggacattgaa gccaattctg 1320

cttcggtggt gagaaaacat gatgcaactg agtataacgg ctggttcact ggagaatttt 1380

ctgtttatcc tgtcgttgga gataccattg gttacattga tgtaatctat tatgaggact 1440

acgatcactt ggcttattat ccagactgca catccgataa gtatattgtg cttacagatg 1500

gttcatggaa tgttgttgga cctggagttt tagaagtgct tgaagataga gtctacttta 1560

tcggcaccaa agaatcatca atggaacatc acttgtatta tacatcatta acgggaccca 1620

aggttaaggc tgttatggat atcaaagaac ctgggtactt tgatgtaaac attaagggaa 1680 Page 58

37324PCT_CRF_sequencelisting 19 Apr 2022

aatatgcttt actatcttac agaggcccca aactcccata ccagaaattt attgatcttt 1740

ctgaccctag tacaacaagt cttgatgaca ttttatcgtc taatagagga attgtcgagg 1800

ttagtttagc aactcacagc gttcctgttt ctacctatac taatgtaaca cttgaggacg 1860

gcgtcacact gaacatgatt gaagtgttgc ctgccaattt taatcctagc aagaagtacc 1920 2022202534

cactgttggt caacatttat ggtggaccgg gctcccagaa gttagatgtg cagttcaaca 1980

ttgggtttga gcatattatt tcttcgtcac tggatgcaat agtgctttac atagatccga 2040

gaggtactgg aggtaaaagc tgggctttta aatcttacgc tacagagaaa ataggctact 2100

gggaaccacg agacatcact gcagtagttt ccaagtggat ttcagatcac tcatttgtga 2160

atcctgacaa aactgcgata tgggggtggt cttacggtgg gttcactacg cttaagacat 2220

tggaatatga ttctggagag gttttcaaat atggtatggc tgttgctcca gtaactaatt 2280

ggcttttgta tgactccatc tacactgaaa gatacatgaa ccttccaaag gacaatgttg 2340

aaggctacag tgaacacagc gtcattaaga aggtttccaa ttttaagaat gtaaaccgat 2400

tcttggtttg tcacgggact actgatgata acgtgcattt tcagaacaca ctaaccttac 2460

tggaccagtt caatattaat ggtgttgtga attacgatct tcaggtgtat cccgacagtg 2520

aacatagcat tgcccatcac aacgcaaata aagtgatcta cgagaggtta ttcaagtggt 2580

tagagcgggc atttaacgat agatttttgt aa 2612

<210> 48 <211> 2127 <212> DNA <213> Pichia pastoris

<400> 48 atgacctgcc aaagtgtaga agagctggat gctattgttg aatcaaagct tagggaggtt 60

gataataaag tttcgaacgg aaatgttgac ttcatcaaac aatatctgat tcaggcgatg 120

aactattatg acaagtatag atctgaaatc aaaaaaattg gacccacaga aaagaaccct 180

aaatactatt gttttcaaga ggcagcgtat gttaactaca aagcttccca agctttacta 240

agagagagaa tacccaagct gcctggcttt ggaggatata aatctgcgta ttcaaaaatc 300

tatcgtgaac tgatagaaat ggtagagggg caagaacatg agattgccca gataaaaagc 360

Page 59

37324PCT_CRF_sequencelisting 19 Apr 2022

ggcttaagga aaaacttttg tgatgataca ttagttcttc gactgagaag tttaaaatca 420

ccatctgcta ctcagcccaa aagtttaccg gattctacac ccacttcaca atttaaacca 480

aaaccttcaa agccttttag tatcacaatc aatgaggaat acatttcggt tgaccaattg 540

tcacgccttc ttaaaacgaa cccgaatgac atactcctca ttgatctacg gtctcgtcaa 600

gagtacgacg tgtatcacat tgaagatggc tccggggtgg acatgtcaat atgtatagaa 660 2022202534

ccaatgagta tcagaaacgg atacacagca gaggatcttt atcaactttc aatggccgtc 720

aatccagatt atgaaaggag attgttcaag aatcggtctc agtatgaact gttggtatgt 780

tatggtaatt atgacaacga ggctactgtt caaatgttca tgactatcat gaataaagat 840

acttccctca agaggcggag cgtctatttg aaatccggaa ttaagggctg gaatcaggat 900

ctgagttttc aagattcgaa accgaatggg tacttaacta gtacgactga ctacttcagt 960

aacactccga aacacacaat tacgcccaaa tcatcaaaat caagttcaaa acctacttta 1020

aaaactactg tcaactctgg gcctgcccac actgttggga tcaataatct aggaaataca 1080

tgttacatga attgcatact tcaatgccta ttagaaagtg ataagtttgt ttcatttttt 1140

ttacaaggcg attataagaa acatatcaat attaatagcc gattaggctc gagaggtata 1200

ttggctacag gatttcattt gttagtgcta ttaatatcca gatcatctgg taaaacagtg 1260

actccttctt catttgccaa agatgtttca acagtgaata agaattttaa gttaggagag 1320

caacaggatt gttttgaatt tttagatttt ctcctggata gtttacatga agacctgaat 1380

gaatgtggga atgaaccacc aatcgcagaa ctcacacctg aagaggaaaa gcttagggaa 1440

gctttaccta tcaggattgc ttcgaccatt gaatgggaaa ggtatttaaa aaacaatttt 1500

agcatagtag aagatgtgtt tcaagggcag tacttctcca gattggaatg tacagtctgt 1560

aaaagcactt caactactta taactcattc agttcactgt ccttgccaat cccattagat 1620

cgacaaaatg tcacactaga tgactgtttc caggcttttt gttctgtaga agaattgaac 1680

ggagatgaca gatggcattg tccaagctgt aaaaaaaagc aggtcgcttt taagaaactt 1740

ggtatctcta gactaccaag tgttctgatc gttcacttta aaaggtttca ggtcaagtgg 1800

gaaacaggtc atataatcaa gatagacaag tttatcagtt atccgttcaa gctatcaatg 1860

gacaaatatt ggcccaaagc tcaatcagaa gaagaactaa gaaacttgga gaagctacca 1920

Page 60

37324PCT_CRF_sequencelisting 19 Apr 2022

tcgagaaatc agaatccccc tttcaattat cgattgacag gggtggctaa tcattttggg 1980

accagaacat catctggtca ctacacatca tatgttcaaa aaggtggcca atggtattac 2040

tttgacgata gtgctgtgac tagcaatgtt gatcgtcata aaatcgtaaa tgggaacgcc 2100

tatgttttat tttatcgacg tagttag 2127 2022202534

<210> 49 <211> 669 <212> DNA <213> Pichia pastoris

<400> 49 atggaagccg tgaatttaca aattgaatgg attagacagg tgcctccagt tactgtggct 60

cttgtagcat ccatgtcaat gacctatttt ttgcaacgca tagatgtatt atcctcaaat 120

atgttcgtgt ttgaaagaca tcgtgtgttt aatgagatgg cctattctcg tttgatacta 180

agtttcttct tcagcgccca ttcgtttgtt ggattctttt ggacattgta cacattattt 240

cagaattcac aggcactcga gctgacctat gaaaactcaa tcgattacct ctactcattg 300

gtgataatag caggtttgat cgtggcatgg gcctcatact tggggggtcc gttcatgctg 360

ggatgggttc tagctgacgt cttgagaacc atatggtgca aacagaatcc caacgaaaga 420

atgtctattt tggggctagt ttccttcaag gcaggatact ttccatttgt aatacttgcc 480

atttcatggc tagaaggaag ttcaagaaat cttctattaa tgctaattag ccaaactgtc 540

agtcaggctt atatttttgg acaccatatg atgcccgaac tacacgggat cgatctgttt 600

ctgcctatat ggaaattcca gtgtttcaga cgtcagagac aaccaccaat tcatcagcat 660

caagactaa 669

<210> 50 <211> 927 <212> DNA <213> Pichia pastoris

<400> 50 atgtcaaagg tggtggtatt cctaaatgga ttattggcaa taacctttac gtttgaactt 60

ctctctgttt taagcgtgcc aatcaccaag catatccaac tttgttctta tcaaggatat 120

aagtttggcg tgtttggata ttgcaccgag aataatatct gcacaacgat aggaatcggt 180

Page 61

37324PCT_CRF_sequencelisting 19 Apr 2022

tatcatcgaa attcaataga cgaattgaga ggcttttcat taccaagtaa tgcaagaagc 240

tctatatcaa gcttgttggt ggttcatttg attggctgtg tttgcacctt tattttatgg 300

gttctaagtc tcatgttgaa tatggataga tttcacagat cattatggtt cttattaacg 360

tgtctagtat ggacttgtgc tttctttttt tttacattat tctccttcct ggtagacgtg 420

ttactatttg tgccacacgt tgcgtttgga ggttggttga tgttggtaag tactgtattt 480 2022202534

ttggcattta caggaaccat tttttgcatc atgcgaagaa ctgtcagctc aagaaaaact 540

catttgaaga actacaacgg gggaagtaca agtttgatgc ggctgcagac gtatatctcc 600

aatagctcta gaggaagctc tgtaaccaat gatgaatacg tctggtttca agaaactcca 660

ttacaagacc tctacccccc agacaatccc aattacgacg acatctacgg aacgactgaa 720

cacgaactaa cccgcttgga cacaatatct cttgaaaggc caagaatagg ccttatcaca 780

aacgaaaatg ccagcggcga tggtggggta gtttccccac cacagaatga cagtacactt 840

ctggaatctt cgggcagaat taggaatggg ccactgggag accgaagtga atttcccaac 900

ggatcaacaa gcgaactttc tgcataa 927

<210> 51 <211> 714 <212> DNA <213> Pichia pastoris

<400> 51 atgaaataca gtgaccaatt aatagaagag tacaaagaat tatggttaac agcgacatct 60

aatgagctta ctagagaatg gtgccaggga actctccacc tgagcaaatt atacgtttac 120

ttgacacaag acttaaagta ttttggggat ggatttcgac ttttaggcaa aaccatttcg 180

ttatgtcgcc gtaggcaatc gcttgtgtca ttaggcaaac atgtggggat gctcagtaat 240

agtgagaaca cgtacttcgt ggattgtatt aacgatctta ctgaacagtt attaagagat 300

gggatgtaca atgctgaaga attagaagaa atcagtggtt taacgttacc tgccgtggaa 360

aggtaccttt tattcatgag atcgatggta gagtcttcta caataactta tgcagaaatg 420

attactgtga tgtttgtaat ggaacaagtc tatctggatt ggtcaaataa tggactgaga 480

agtaaacctg acaacttgca ttggtggttc aatgaatgga ttgatataca tagtggggag 540

aactttgaaa gctggtgcca gtttttaaag gatgaggtag accgctgtat acaggagttg 600 Page 62

37324PCT_CRF_sequencelisting 19 Apr 2022

aaggatgcta atagagatga tctcgtggcg agggttgagg agatttttag agaaacatta 660

gaacttgaag tcgaattctt taaaagttgt tacgatatca cggacgatga atga 714

<210> 52 <211> 357 <212> DNA 2022202534

<213> Pichia pastoris

<400> 52 atgcactcga aatttaggtg ggtatgtgtc gatactcaat tctgcacaca ccaccaaaat 60

ctgtcgcctt tctcttatat ctccaacccg agtccaatgt cattttctta ccttgaaggc 120

aacatcgatt ttaaaggaca ggaacttgca aacaggatca ctaaaaaact aatcacattt 180

ggtgcaatta ttagttttct ggtaggattt ttgagtgaca acatcttata cactgtatac 240

actttcgcag cttttggttt attgactgct tctttggtta ttcccccttt tagcttctac 300

aaaaagaacc ctgtaacatg gttaccaaag aaatccaaaa tagagattca gcattga 357

<210> 53 <211> 3423 <212> DNA <213> Pichia pastoris

<400> 53 atgacagact ctgttaactc tgatgattct gatctggaaa tcatagaggt gactgagcct 60

actccaaaag tggacctttt ggcccccaat ccagcattta attttactgc ccccataagc 120

aacagtaacg gcacaactcc aataaggaga aaacttgatg accaatccaa ctccaattct 180

tttgccagac tggaatcgtt acgggaatca tcagtgaaac cacaagctag tacgttcaat 240

agtagtaggt tcatccccca agccgaccaa ttttccaata atcagaataa tgaacttgat 300

aacaacaatg gattcgccga ctggatttct aagtcccaac ctgaatttcc ctttccactt 360

aatgatggac caaaaaagtc cagcaatcaa cctacaaact caaattttga agagatcatc 420

gatttaactg aagatatcga gataaataca tctgtccccg catctacatc atcttctacc 480

ccagttccct ccagcacaca gaatcagagc catcatatag ccaacaacaa cacagcacaa 540

gatgcgcata tcttccaagg gaaacgacct ctccaatcat attcagatga tgaagacgaa 600

gatttgcaaa ttgtaggatc caatattgtt cagcagcctc taggaattat gccaggaact 660 Page 63

37324PCT_CRF_sequencelisting 19 Apr 2022

ttcaacgccc ctgcaaacat actccatttt gacggttcaa accagaatga acaagccaga 720

tggctggact tgcggataaa agatttgtta gataatcttc acaatcttcg agttcatgct 780

cagtcgaata ttatggagat caataggttc atttccactt tggggcattt aaacagagaa 840

gtttcagagc tcaatctaag atatcaatct atcgtgaaca atcctcaggc gaccgctaat 900 2022202534

aatcaaggat acctcactca gcttttgaac aggattcagg agcttactaa tgaaaaagcg 960

cacatattta gagagatgga tacatccaag ataaaacagc aggagattca cagaagaatc 1020

catgctctct cgtcaacaat tgacaaactg aaaaaagatc gtgaacttat ctttcgaaat 1080

gctcaaaatg cttttcacgg tgatatgaag aatgaagttt tggaaggcca gtctttcatg 1140

gatgcaattc atagggcaaa tagcttgggt tatgcttcaa atatttattc tcgttctgat 1200

gaagacgctg gaagcttaca acggcttctt gaaaatatcc agcccgatat ggaggacaaa 1260

gacgatgatg aattggctaa aactccgaag gagttcaata ttcaactgct gaagcatcag 1320

agagttgggt tagattggct acttcggatg gagaagtcaa ccaacaaagg aggcatttta 1380

gcagatgcca tgggcctggg aaaaaccatc caggctatta gtattattta cgcaaacaaa 1440

tggaaaacac aagaagaagc cgaagaggag gcaaaacttg aagagaaggt tagatccgaa 1500

aagtctacat cagaaacgaa tggagaggtc agcaaaacgt caacggcaaa gtcggaaaag 1560

aaacccatcc aaggagacga aggatatttc aaaactacgt taataatagc accagtttct 1620

cttctacatc agtgggagtc tgaaatcttg ttaaagacga aaccagaata caggctaaaa 1680

gttttcattt atcacaagca aaaaatgtcc tcgtttgaag agctccaaca gtatgatata 1740

gtattaacat cgtatggaac tctgtcttct caaatgaaga agcattttga agaggcaatt 1800

aaggaggcag acctacagcc caactcttca tccataccag cagaagactc tggaggcata 1860

tctttcaagt caccattttt tgcaaaagaa acaaagtttc ttcgagtcat tctagacgaa 1920

gcccataaga tcaaaggaaa aaatacaatc acttcgaagg cagtcgcttt ggtgaagtct 1980

aaatacagat ggtgtttaac gggcacaccg ctacaaaata aaattgaaga actatggcct 2040

ctacttcgat tcttgagaat taagccatat tatgatgaaa agcgatttag aactggcata 2100

gtattaccta taaagagttc catgtcaggc aaatatgatt ccacagacaa gaagattgct 2160

atgaggaaac ttcatgccct acttaaagca atcttgttga aacgaaacaa agattcgaag 2220 Page 64

37324PCT_CRF_sequencelisting 19 Apr 2022

attgatggag agcccattct caagttaccc aagaagcata tcattgacac attcatagaa 2280

atggaagcaa aagagttaga cttttacaag gatctggaag gacagacagc caaaaaagcc 2340

gaaaagatgc taaacgctgg aaagggacaa ggaaatcatt attctggtat tcttatcttg 2400

ctattgagac tgagacaaac ttgttgccac catttcctcg tgaagttatc tgagatgaag 2460 2022202534

caagaagcca aattgaaaca ggaagttgct accaagatgc cacaattggc cacacaacta 2520

tctcctgctg tggtaaggag aattaacatt gaagcagagg ccggatttac gtgtcctata 2580

tgtttggata acatcataaa tgagaatgct tgtatattat acaaatgtgg acatgttgtt 2640

tgtcaagatt gcaaagacga tttcttcacc aattatcaag agaatgaaac tgatgacggt 2700

cttagagtgt ccaaatgtgt gacctgtcgt ttgcctgtca acgaaagcaa tgtaatcagt 2760

ttcccagtct acgacaagat tgtgaaccag catatttcag tgatggatat agttaaaagt 2820

gagtctccag tgttgtcaaa aattgaaatg attcaacaac tgatccggga gaacaaaggc 2880

gtcttcgaat cgtctgccaa gatcgataaa gcagtggaaa tgatacaaga gttactgaga 2940

gacaatccag gggagaagat catagttttt agtcaattca caactctctt cgatgtcata 3000

gaggtaatac tcaaagagaa caacattaaa ttcattagat atgacgggtc aatgtctctt 3060

agcaatagag atgctgccat tcaagagttt tatgagagta cggagaaaaa cgtaatgctt 3120

ctttctttga aagcagggaa cgtggggttg acattgactt gcgcctcccg tgtcataata 3180

atggacccat tttggaaccc atatgtggaa gaccaggcca tggatagagc ccatagaatt 3240

ggccagttaa gagaagtttt cgtctatcga atgttgatca agaacaccgt cgaagataga 3300

attttgacca ttcaaaatac gaaaagagaa atagttgaaa acgctctgga taaccagagt 3360

ttgaatacga tatccaagct tggcaggaac gagttggctt tcttatttgg tatcggcaat 3420

tga 3423

<210> 54 <211> 1080 <212> DNA <213> Pichia pastoris

<400> 54 atggagtgta aaaaagtcaa agatcgccta gtcacggaat acttaaagat tgaatgtagt 60

Page 65

37324PCT_CRF_sequencelisting 19 Apr 2022

cgacttaacc gaaggatacg ctccctgaaa aatccaaaag ttgagcaagc cctactgcaa 120

ttcaagaact cacgtttggc tcacatgaga aaggctcatc tggatggaat aagaaaccca 180

cagtatacgg atgacgccat ctttcaggca ttggaaacca tggatttgga ccacatattt 240

gagaaggcag gtagtcttta caactcacag caacaagatg aatcaaaaaa agattccctg 300

gatgaaacag atttcaccgt ggtggcgttg ctagattggt tcaagaatga cttcttcaaa 360 2022202534

tgggtaaaca agccaccttg tcctgtttgc catagtgaag atgaaagccg cataagaatg 420

gtcggatctg caaggcccac tagtgaagaa ttgtcgtacg gagcaggggt cgtagaggtg 480

tttaattgtg accattgtag ctgtgcaatc agatttccaa gatataacga ccctaagaag 540

ctcctgagaa ctagagctgg acgatgtggg gaatggaata actgttttct gttgtgtcta 600

aaagccttgg gtctgaaagc tagatgtgtg aggaatgtgg aagatcatgt atggagtgaa 660

tactactcgg aacatctcaa gcggtgggtc catctggata gttgcgagaa tgcctttgat 720

caaccagaac tatactgcaa aggttggggg aaaaagatga gctattgttt tgcttttgat 780

gacactctca tagaagatgt gagtgccaag tacattactc aaggtagact gcctaaaatg 840

ctagacgacg aaaccatcag aatatgcttg tattttttca accaggaagc tcttaagatg 900

gtgagtgaaa atccagaggc attctactcc gctttggtta agtatcacag atgtctgtct 960

gcgaatagaa aagagagcgg gtcaaaatca cgagccgtga atgctagttt gacttcattg 1020

ttaccacgac aatctggtag cgcatcctgg acgtctgaga gaggcgaaaa cggactttag 1080

<210> 55 <211> 819 <212> DNA <213> Pichia pastoris

<400> 55 atgcctataa aggggcggtt caccaaaaag aagccaaaaa ggaaagatga gccaaatcga 60

ccgtccccca cccagttcat caaaaaaata gcctcattga aaaagcagac caggagagat 120

gaggccctgg atgtgctaca cgaactagca gttgttgtgt cacctttgat gaaagagaac 180

ggtttcactg ttggattatt atgcgaaatg ttcccgaaga atgcctcttt attggggctg 240

aatgtgaata tgggttcaaa gatcatgatc cgattgagac ctagccacaa catgaacttg 300

tttttgccaa aaagagagat catcggtaca atgctccatg agttaaccca taatcgcttt 360 Page 66

37324PCT_CRF_sequencelisting 19 Apr 2022

tcggcccatg atgtaaggtt ttatgacttt cttgagggtc tcaagagcag gttttttgag 420

attcaggtga aaggatcttt acaaactaca gggtatgtta actttagtga agttctatct 480

ggtaatgcgg cgagagggca actgattcaa aaggaaaaag agaaaggaca aagattgggt 540

ggtaataagc atgcaaaacc tatgagagtc ctaatcttgg aggcggccga gaagagaatg 600 2022202534

atagactcta aatggtgcgg aggagctagc aatgaagtag gccttccaaa aattgaagat 660

ctaatggacg atgaagaagc tcaacactct gaactaaagg aagagaatac aaagaaggtc 720

agaaaaattg ttcaacctag caaaaagaaa attgtagatt tggaaaacct accgaatggc 780

aagtccatta ttattgatct aactaatgac gatgactaa 819

<210> 56 <211> 1719 <212> DNA <213> Pichia pastoris

<400> 56 atggaacaca attgtctgaa agtcaatgaa ttggcgctcc agttggctca atcactgcag 60

aacagcaaag tcagcacagc tgatcctcta aagaagagga caagcagcta cagaggcctg 120

agtagcgagc ctataatcac agaggaagaa ccaacaatca agggcgacta taatagattt 180

tacagtcagt cttcagataa gcaagtattg gacaataaac catggttgca ggatggaaac 240

tatttcaaga ctgtatacat ttcaacgata gcactactga agatgatgtc tcatgcccgg 300

tccggtggtt caattgagat tatgggcatg ctgacaggta aggtgtttgc caacacatta 360

gtcgtaatgg attgctactt acttccggtt gaaggtacag agacacgagt gaatgctcaa 420

gcggaaggat atgagttcat ggtctcttat ttggataact taaaggaaat caagcataac 480

gagaatatca taggatggta tcactctcat cctggttatg ggtgctggtt gagtggaatt 540

gatgttgcca ctcagaattt aaaccaaaag tttcaagatc cctacctggc gatagtgatt 600

gatcctgaaa gatcagtcag acaaggattt gttgagattg gagcattcag aacgtttgct 660

gagccagccg ttggaagatc gtcgtcgtca gtttcctctg caagtggtgc aggaattagt 720

gatgttgcgt tttcttccgg tagaaacagt gcatctggaa tgtcctcagt tctgagtgca 780

agtaatatta gcattgccga agagctaagc aaacaatcga tcacccaaaa tgtttttgac 840

Page 67

37324PCT_CRF_sequencelisting 19 Apr 2022

agaactacta caaagattcc caagggcaaa atgactgatt ttggagctca ttcaggaaaa 900

tattactcgc tagaggttaa ggttttcaga tctccactgg aggagaaact actggatacg 960

tttggttcta aaacctggat taaaggttta acgaactact ccaacgttgt taatgccgag 1020

gaaactcaag tggagttaat gcataaaata atggaagcca cggagaactt acggaaggaa 1080

tctccttcta aattgccatc tttggtgatg gggaacctga tttattcagg tgcctctcaa 1140 2022202534

ggaacaacag ggaaccgcaa gcgctcaatg tccaaatctt ctatttattc gggtttacaa 1200

gcttcatcgg gtatacccag ttctaggtat cctacgaagg gaaaaaatat gagtggatct 1260

caattcaatg atgacccgct agcaagatca ctggataaaa taccgccaga tagtccagat 1320

caacagtacg atggcgcatt atccattcaa caaccgaaaa gagcatataa tacacatact 1380

tctagagcag gtgggttggc cagcgttctg tcctctggga gtatggatcc tcaaagttac 1440

tccatggtag gacgaatgag tctaactaat caatcgccgg ggacagctct gagaggccta 1500

aatacacctc ccaacaaacg accgcagaga aaccctggtc atacaagctc aggtcaagga 1560

ggaacgcctg gaggagtcag tcggtccaaa gagaaaatta acaagccaat aggtataagc 1620

atgattagca aggatttcaa ggttgtcatc tcacaacagg tcaaccagat gctacgtcgt 1680

cacgtccaga atgacctttt tggatccaat agtccctaa 1719

<210> 57 <211> 2181 <212> DNA <213> Pichia pastoris

<400> 57 atggatcatg cccaacgatt gctagaacta agtttttaca atcaaagtct gggcaaatca 60

gtgatagcaa agaaatacag aatagaatcc tctcgatatt tgaatgaaca actggacaag 120

tccttgacaa gagataatga tctgattgga ttatgccgta tagcattaga caacaagttg 180

accatatcag ataagattat atggatgagc tctcaagttg aagacaactt ctttccgcca 240

gtttttcaag gcttgaagac gtatattgat agcgacgaga tttatcaaga gaaactttta 300

agcgtaccag cggattttga accaatagtt gaatggaaga gttgcacaga gttgcccaat 360

gaatggtcaa acaatggtgt ggacaattta tttcaggatt ctttagatga ctgttcgttt 420

gtagcttcat ttctatcctg caacaatatt ggtatccctc tcatggataa agtcattccc 480 Page 68

37324PCT_CRF_sequencelisting 19 Apr 2022

cacaaaaact cgttcaaata tgcggttaga ctgactttca atggttgcga aaggttggtg 540

tttattgata gccgtttgcc tttgcttagg aatacttcca agactttacg agtgtcaagt 600

ttttctaaca aagatctctt atggcctagc atcatcgaaa aagctttcct gaaaatgtgt 660

gatgatgggt acaagttttc aggatcaaat tcagccattg caaactatgc tttgactggc 720 2022202534

tggatccctg aagtcattaa aacttcttca tgtacaatag cagatattag ccgattgcat 780

gaggattttc ggaacggaaa cgtagtacta tgcttgggaa cgggcaatct gaccgagcga 840

gaatgcaaac agtatggatt gatccccaat catgactatg ctgtcactaa actatcattt 900

acgaatgatt cagaatacaa gtttgacatt cgtaatccgt ggactaaagg gcagaaagca 960

gtgacaatta cagatctttc aacctttgaa gttatctacg caaacagaaa tcctataatg 1020

ttttcgcaca tgaaccagct aagcggtatc tgtcaaagtc aggttaatga agagttcata 1080

gatctaattc ttaaccattc gcagtatacc ctaggcaatg acggtaattc tacaattgat 1140

gtgattcttt tctttgaaag acattcgtta agaaagaaaa tcagtgcaga gtctcgtatt 1200

gagattttcc aatcagaagg cgaaagacta atctccagaa gaaataaagc aagcaaggaa 1260

tgtgtttcta ataataccaa ctttcatttc ataacaatcg aactgaaacc gttagaaaag 1320

gtaactgtgg taatagatat cggcgagtct tcgattcgaa gccatccatt tactctaaag 1380

gcttttgcca atgattcaac tataactttg aacaaagcac tttctagacc tggttgtttc 1440

aagcaaatgg acctagagct aacgccctta aactctggtg ggaattggga taattatgct 1500

tattacaaaa atccacaact catagtcact cttcacggag attcaacgga tgaagctcca 1560

tttgaatctg ctgttttcag caaaagtgat aagaccctat ttacgtatac agtgttttgg 1620

aaaagtgacg atccagactt tcctttcatc actgacgcaa gcaagaacaa gctcgtaagc 1680

acagacaata agtataaata cagatcatgt acaagatcaa gagttgtttc ttgcgacaaa 1740

agctatttgt tcgtgctgag ctcctacgaa cctgatgcaa ttgagtcttt caaagtattt 1800

tttcaatgtt cccacgattt ttctatagag tgggctgaga cgtcgcttgg gcttttcaca 1860

aaggaagaaa ctttctcctg gaaggaccaa ttagtcaagg agttcattat tcaagtctat 1920

aacccttcaa agttgaaagt tcacgcagta aacaccaaca acaaacgcag atcaaaacta 1980

aattgctctc tctcattcca aaacacatta atcagctctt tgcaagacta cacagacaat 2040 Page 69

37324PCT_CRF_sequencelisting 19 Apr 2022

ctctatggat gctttattag cgggaacttg gagattcccg gcaagtatct attacaagtt 2100

cataaaaaca ttatatctaa cgaagaatgt ttggtcgaaa ttggatctag ttcgtcattt 2160

gagttatggg aacatcatta a 2181

<210> 58 2022202534

<211> 1137 <212> DNA <213> Pichia pastoris

<400> 58 atgttgaaaa ctcgatttca ttccagaaag ggttttgtaa tctacagtgg agatgatgaa 60

gagagtgacg aagagagtaa acaatggatg tttcccgagt cgacctttgt aaccaatggg 120

tttgaccaat tgttcaaggt gagaaatgtc aataccatta atgacgacga tgacggctac 180

caatcgttcg atcaaccgga ttgggcgcaa gatttaaccg cagatactca gtatcttgct 240

ttaggtgacg aaggggagaa tcatcgttca caacaagaga taggcaacag gaaaagagcc 300

aacaaaaagc aaaagaagcc aactaaagca aagacaaaac gtcaacaaag acgcacagcc 360

aaaaatgatc aatccacgga acgatctgcc atttcacaac cttctaactt aagtacactg 420

aactccttac tcaaatctgt tcggtctgaa ctttccaatt ctgatgggag tccccacaca 480

ttctacgatg tatctctcta tgaagaagat ctgaacaacc tagctgatga cgaatggttg 540

aacgataata acgtctcgtt tatctacgag tacattgaaa gattttacat tacccgttgt 600

ttgagcgaca agcttcaatt ttcatcaaag aagatggtca attctcaaat aatactcctc 660

cgaccttcta tggttttttt gctggcacat tcaactccaa aagatatcca ggattttctc 720

ccaccgttgg ataagtctgg ctttatattc cttcctctga acgacaatga tgatctggaa 780

atggctgaag gtggatccca ttggtgtctt ttagttgtag ctgttcacga taacaaatgt 840

ttcctctatg actcattaga gaatgccaat ctcacagagt ctgttgcgct tgtgtctaag 900

ctgtccactc tgctaaacag gcgaatacaa ctcgttgaaa atacacattg tcctcaacaa 960

ctcaatggca gtgattgtgg agtaatcaca acccaaatta cagcactact ggtatcccga 1020

ctgctttgtg ttttgccggg acatcctata aatttggatc ttcaaaatgt agctatcaac 1080

gcaataagcg ggagaatctt catgttaaaa ctcctccaac atgttctgaa caattaa 1137

Page 70

37324PCT_CRF_sequencelisting 19 Apr 2022

<210> 59 <211> 408 <212> DNA <213> Pichia pastoris

<400> 59 atggcaccac cagtccctgt atatacgaga gatgaagtca agatgcaatt tccacagtac 60 2022202534

atgatgaaat ttttgccttc aaactgtgag ctgtactcca tcatccagaa ccaatgtacc 120

ttctctgctg acgagataat atgtgtgccc ttcaagaggg tgtttgccaa atgccggagg 180

ggaaaccaag aagccaagag gaacataata ccagagaatg gaggactgaa tttaactgga 240

aagaaactaa tcccaagaga atacacagtc attgaagtta cggactccct aacgaacaag 300

tacgacaata gtagcctcat ggacagattt tttgaggcag aaagagattt aatgataagg 360

tttcaagaat atgaggaacg gaacagtaag gaaggagaaa taaagtag 408

<210> 60 <211> 1449 <212> DNA <213> Pichia pastoris

<400> 60 atgctcagac agtttgctgg aagggagttc aagcgtcggt tttctacggg aatcaagacg 60

atgccaacaa agcttaccaa actgccaaat ggtattcgtg tcgtaacgga cgaagctccg 120

ggccatttta gtgccatggg cattttcgtt gatgctggtt caagatatga gagccagttt 180

ccagaattaa ccggccactc tcacatcatc gatagacttg cattcaaatc aacatccaaa 240

ttcgatggga aatctatggt agaaaacacc aatcatttag gtggcaactt tatgtgtgcc 300

tcttcaagag agtcattgat ataccaggct tcagtgttca acaaagatgt ggacaagatg 360

gctgaaatcc tcagttctac agtcaaagaa cctttattta ctgaggagga agtttctaat 420

cagatagcaa cagcagatta tgagttggat gagttatggc tgcaacctga cctaattctt 480

cccgaattgt ctcaacaggt agcttatgga tcaaaaaatt tgggttcccc gctgctctgt 540

ccgaaggagt ctttagcaaa catctcaaga gaatcccttt tgaagtatcg tgaaatattt 600

tttagacctg agaacttggt cgttgctatg ttgggagttc cccacgagaa ggccttggaa 660

cttgttgata aaaatttagg cgatatgaaa tctgtcggtt ccagtccagt ggtcaaagaa 720

Page 71

37324PCT_CRF_sequencelisting 19 Apr 2022

cctgctaaat atacaggagg agaactttct ttgcctccag ttcctcctat gggtgggctt 780

cccgagtttc atcacatata tcttacattt gaaggtgtcc ccgtggactc tgacgatgtc 840

tactcactgg ctactttgca gatgctcgtc ggtggtggtg gatctttctc tgctggtggt 900

ccaggaaaag gaatgtatgc cagagcatac acgcgagttc tgaatcagta cggttttatt 960

gaaagttgca attcatatat acacaatttc tcagactcgg ggctgtttgg tctctcaatt 1020 2022202534

tcaagcattc cgcaggcaaa taaagttgtt gcagaactct taggtcatga actgagctgc 1080

ttgttttctg aaaatccggg caaaggtgct cttaccaatg ccgaagtaaa ccgtgccaaa 1140

aatcagctac ggtcttcttt gttgatgaac ttggagagca agatggttca attagaagaa 1200

ctaggaagac acattcaagt ttatggcaga aaagttgatg tcacagagat gtgtgataaa 1260

atcagcaaag ttacaaagga agatctagtt gcaattgcaa agaaagtctt gaccggaagc 1320

aacccgacta tagttgttca aggtgacaga gaatcttatg gagacattga gggtactttg 1380

gcatcttttg gagttggttt agatgccgct tccaaagctt caaagaaaaa aacgagaggt 1440

tggttctaa 1449

<210> 61 <211> 390 <212> DNA <213> Pichia pastoris

<400> 61 atggcaatta tcaagttcaa cgcaggcaaa gtcaagattg acgaggaaac caagctttgt 60

acacccttgg caacaagagg agaaataatc gtccaattgt cggctgaggg cgaagagttt 120

tatgatttca aatgggtccc tactgagaac acagctggtg aaggtaacca gtcagagaca 180

ttcttggtca ttccgggcga tgtgacgtgg aaacacgtca aaagttgtaa agatggtaga 240

gttttcaaat tgacattttt gagtagtggg gcaaagagtt tgttctggat gcaagatgat 300

aatggaaacg aggatgaccc atcagagttg acaaccaaag ataaggaaat tagtgaaaaa 360

attaccaagt tgttcgacga agaagagtga 390

<210> 62 <211> 2184 <212> DNA <213> Pichia pastoris Page 72

37324PCT_CRF_sequencelisting 19 Apr 2022

<400> 62 atgaaacact tggctgtcca taagtacaag gtaggagcca tcgcagctgg cttggttgtc 60

tcctataaaa tctttgccta ccgcgctgcg tcttcctcct cctcaaacgt catcaacttg 120

accaatatgg caaaaactcc aatcacttta aaaccccctc aggctccact ccgctgggac 180

catactccag agcagatcct tgccgaaact gataagtata tatctaccag tcaagaggtt 240 2022202534

gacgattggg tggcaaacag ctttgccact gccaatgtgg acaccatcaa gaaaatagcc 300

gccgctgaga atgaacaata cttgccactg tgtcaattga gtttttatca acatatctcg 360

gataaccagg acgttcgtaa tgccagtact gttagtgagg agaaaattga taagttctcc 420

atcgaatcca accttagaga agatgtgttc aaaacagtga acaaagtgtt caaacaggtt 480

caagaagatt cggaactcca aaagaccttg gacccagaat ttaggcgttt actagaaaaa 540

ttgaacctag gttacgtgag atctggttta gatttatccc aggagaagag agaccaagtc 600

aagagtttga aacaagaact atcaaccatt tcaatcaagt ttaataagaa cttgggagag 660

gaaactgaac acatttggtt caccactgag gagttaaaag gtgttccaga atcagttgtt 720

gagcagtttg aaactaagaa tgagaatgat gttacttacc acaagatgac atacaagtat 780

cctgacctgt tcccggtact aaaatatgcc gttaatccag ctacgagaca aagagctttt 840

gtcggggatc aaaacaagat acctgaaaat tcaggattac ttgtgaaagc cgtcaatttg 900

agaaacgaac ttgcaaaagt tttgggttat gatacctatg ctgactatat cctggaagtg 960

aagatggcca agaactccaa gaatgttttt gaatttcttg atgatgtaag ggaaaaactc 1020

agacctctcg gagagaagga actgcaaaga atgttgactc tcaaggctaa cgacccaaat 1080

gctgttgata aggaaaatta ctacgtctgg gatcatcgtt actatgataa caagcttctt 1140

gaatctgaat acaaagtgga tgagcaaaag ctggctgaat actttccaat ggagtccacc 1200

attgaaaaaa tgcttgccat ttacgagcac ttgttcaatt tgcagtttca acaagttgac 1260

gattcggaga aacaagtttg gcatccagat gtaaaacaat tctccgtttg gaaaatcgat 1320

aaccctgatt ctcctgaatt tgtgggctgg atctattttg atttgcatcc aagagaagga 1380

aaatacggtc acgctgctaa ttttggaatc ggtcctagtt acatcaaaga agatgggagt 1440

aaaaattatc ctgtcactgc tttggtttgc aacttttcta aaccatcaaa ggataagcca 1500

Page 73

37324PCT_CRF_sequencelisting 19 Apr 2022

tccctattga agcacaatga agtcactaca ttcttccatg agctaggaca tggtatccat 1560

gatttaattg ggcaaactag gtatgctcgt ttccatggta cttcagttgc tcgtgatttc 1620

gttgaatgtc cttcacagat tctagagtac tggacctgga ctagagatca actcaagtct 1680

ctttcccaac attacaagac aggagaagcc ctctccgatg aactcattga ttcgctagtc 1740

aagtccaagc atgtcaatgg cgccattttc aatcttaggc agttacactt tggtctcttt 1800 2022202534

gacatgaaac tacatactgc caaagagcct gaatctttag atgtgacaag gttgtggaac 1860

gaattacgtg aggaagtcgc tctggttaag aatggtgacc aaattacgaa aggatacggt 1920

tcatttggac acctaatggg cggttatgct gctggttact acggatacct gtattctcaa 1980

gtgtttgcca gtgacattta ttacaccttt ttcaaagctg atccaatgag tacagctcaa 2040

ggtatcaagt accgtgatat cattcttgcc agaggtggat caagagagga gctagataat 2100

ctcaaggaat tacttggaag agagcctaca tctgatgcct ttatgactga gcttggagta 2160

gaaaatggtg cgtccaagtt gtaa 2184

<210> 63 <211> 2766 <212> DNA <213> Pichia pastoris

<400> 63 atgcgttttt tggtctcatc ctttcggccc ttcagacata caatttcgtc gcatatctca 60

atgggccagg ctctgtctgc cattcgtgta tttcataaaa attctcactc acgtacccaa 120

ggtttaaggc gccactctca ctactgttgc caccgcaaga tagatatgag tacttctact 180

aaacttccag agcgtcaatt gctaccagcc aatgttaggc ctaccaaata tgatttgaca 240

ttggagccct tattttctac cttcaagttt aacggagaag agactataca tttagatgtt 300

caggaggact ccagttctat tacgctacac gctctagaca tcgatctcca agattcacta 360

ttgataactt caaacaagtc taagactccc ccgcttcatg tgacaagcaa tgatgatgac 420

caatcgctca cttttcaatt caaagagggt actctagtaa agggagataa ggtgcagctg 480

cagttgaaat ttgttggtga attgaatgat aagatggccg gtttttaccg ctcttcatat 540

gaagagaatg gagaaactaa atatttggca actacccaga tggagccaac agattgtcgt 600

cgtgctttcc cttcctttga tgagccatcg ctaaaagccg tattcaacat tgccctcatt 660 Page 74

37324PCT_CRF_sequencelisting 19 Apr 2022

gctgatcaga aacttacttg tctctcaaac atggacgtga aagaggaaca atctctcgga 720

gatagaagga agaaggtgat attcaatccc actccactaa tttctactta cctaattgct 780

tttattgttg gtgatttaaa atatattgaa gccgactata actatcgcat tcctgtcaga 840

gtttatgcca cccctggttt agagaagcag ggtcgttttt ctgtcgagct tgctgctaaa 900 2022202534

acattagaat tctttgagca acagtttgat attgattatc ctcttccaaa gatggacatg 960

gtggcgattc atgatttcag tgcaggagct atggaaaact ttgggcttgt tacctataga 1020

gttgttgatt tgctgtacga tgaaaaaaat tcaaatttgg ctactaagca acgtgttgca 1080

gaagttgtcc aacacgaatt ggcgcatcag tggtttggta atcttgtcac aatggagtgg 1140

tgggagggcc tttggctgaa tgaaggcttt gctacatgga tgtcttggta ctcttgtgac 1200

aagtttttcc ctgattggaa agtatgggaa caatatgtta cagattcttt acaacaggct 1260

ctggctctgg acgctctacg tgcttctcac cctattgaag ttcctgtgaa aagggccgac 1320

gagatcaatc aaatttttga cgcaatttcc tattctaaag gatcctcctt gctaaaaatg 1380

atctccaaat ggctcggaga ggatgtgttc attaagggag tctccagtta tttaaaaaag 1440

cacaggtatg gtaatacgaa aaccaccgat ttgtgggaat cgctttctga ggtgtctgga 1500

aaagatgtgg tcaaagttat gagtatctgg actggtaaaa ttggatttcc aatcatctca 1560

gtaactgaaa atgcaaaccg tatcactttt actcagaaca gatatttaac tactggtgat 1620

gtaactcctg aagaggatac gacgatttat cctgtttttt tgggactcaa aacagaaagc 1680

tcaactgatg agtcgctggt ccttgactca aggtcaatgt cagtagatat ccagaattct 1740

gactttttca aagttaatgc tgaacaagcc ggtatttaca ggaccaatta tgcaccagag 1800

agatggatca aacttggaaa gcaacctcac cttctaagtg tagaagaccg tgctggtttg 1860

gttgcggatg cgggcgctct ggctagttct ggtcactcat ctacaaggaa ctttttgaac 1920

cttgtaaatt catggaaaga tgagtctagc tttgttgtct gggacgaaat aacttcccgt 1980

gttgcagctt taaaagcagc ttggttattt gaatcccaat ctgacattga cgccctgaat 2040

gctttcgtaa gagaccttat ttctacgaag atcaaaagta tcggatggtc attcaatgat 2100

aatgaaccat tccttgaaca aagactaaag agccttctat atgctactgc tgctggtgca 2160

aaagtaccag gagtagttaa atcagcattg ataaactttc aaaaatacgt tgctggtgat 2220 Page 75

37324PCT_CRF_sequencelisting 19 Apr 2022

aagactgcca ttcaccctaa cataaaggca gttacgtttc aaactgttgc ggcccaagga 2280

tctgaaaagg aatgggatca gttactcgac atctacaaga accctgtatc tattgatgag 2340

aaaattattg ctcttaggtc tctcggaagg tttgaagatc ccatcttgat cgcaaagacc 2400

ctggcactgt tatttgatgg ttccgtaagg tcacaagata tttacgtacc aatgcaaggc 2460 2022202534

cttcgtgcga ctaagatagg agtagagtca cttttcaagt ggttgactct taattgggac 2520

aagatttata aattgcttcc acctggtctg tcaatgcttg gttctgtggt tactatcagt 2580

acttctgggt tcacttcctt ggatgatcaa aagcgtgtca aagatttctt tgcatcaaag 2640

gataccaaag gcttcgacca gggtttggcc caggcgttag acaccatcca atccaaggca 2700

agttgggtac aacgtgactc taggaatgta tccgattggc tacgtgagca gggatacaaa 2760

aaatag 2766

<210> 64 <211> 1803 <212> DNA <213> Pichia pastoris

<400> 64 atgataagga tatccttgct gaaaagagca ctgtttccct acgggcgact accaatgcat 60

aatggtaggt ggtattcaga cataggtggc ggaaattcaa ggaatcggaa cgaacagaaa 120

ccaaaattgc ctgtaccaac tagtaatgaa gttaaggaca atgagtcaaa cccggacttc 180

tttattaaaa acggctttag atcagctgat attgcagaga catcctttgt gaaagacaag 240

ggtgctacag tcgaagagga acgtaataca tcggacagtt cacacgaatc tcctcaactt 300

aattttaagg aaaccaacga cgaaacgaat tcaacgatcc aaccaccagt ggcaaaatta 360

cccaccccaa agcaattgaa acaatacctg gataggttca tcgtgggaca agagaagtgc 420

aagaagataa tgtcggtcgc agtttacact cattatgttc gaataaataa ccaggctcag 480

aaacggaatc agaaggtcga ttcctctgaa gaaaatgttg agaatgggtt tccaaatgtt 540

actaaagaat ttgaggacga aaatgaccca gattatgttc cggatttgga gaaatcaaat 600

gttcttttgc tgggaccgtc tggatcaggc aagaccctga ttgctaagac tctcgctaaa 660

tgtctgcagg ttccatttat aattcaagat tgtacctcct tgacccaggc tggttatgtt 720

Page 76

37324PCT_CRF_sequencelisting 19 Apr 2022

ggcgaggata ttgagagctg tattgaaaag ttgctaattg attcagacta cgatattgaa 780

aggtgtgaaa agggaattat tgtgctggat gaaatagaca agttggccaa gccctctgtc 840

tatacaggaa ccaaagatat tgcaggagag ggtgttcaac aaggcctttt aaaactggtt 900

gaaggtacta cagttacggt tcaatgcaag aggagcaatg ctcctgatca taatcagttc 960

ggattgaatg gcaaagctac aaatcaggac aaggaaaatt atatcgttga cactacaaat 1020 2022202534

atcttatttt taaccctggg agcgtttgtg aacctagata agattgttgc ttataggctg 1080

aagcagaact ctattggatt cgatactgat gagtcgaaag atatttctga aacagactca 1140

gtttccgaca aatctacatt agaatatgtt acacttccag atggatcaaa agtttcagct 1200

ctggaacttg tgtcttctac ggatctacag aattatgggt tgattccaga actgatcggc 1260

aggcttccga ttgtatcttc actttctcct ttaacagttg atgatcttgt ggctgtcctg 1320

actgagccca ggaactcgat actaaagcaa tatgtgcatt tctttgacac tgtcaatgtc 1380

aaacttgcta tcacttccaa ggcaatcaga aggatagccg agatctcgat caagaatggt 1440

acaggtgcaa gaggtctcag agccattttg gagaaactgc tactcaatgc caagtatgat 1500

tgccctggta gtagtatttc atttgtgtta gttgatacag atgttataag taagtctatc 1560

gatgagaata aggaaacggg ggaattcgtc ttcaaagatg gtgagccaaa gtattactcg 1620

cgtggagaat tattttcctt tttcaatgag ttatcaaaag aagacgaaaa actcaagaca 1680

tcaattgaaa agatgtgcca aataccactt tccaagaatc gcatagttta ctccgaagag 1740

gagcaggcaa ggttggattc ttctaaacct ctcgccgtga agcactatga acctttcatt 1800

tga 1803

<210> 65 <211> 2322 <212> DNA <213> Pichia pastoris

<400> 65 atgagcttca acctgctaag tgttccttta cgaacgtcaa agccgatacc gttaggcgaa 60

agcctaaaag agcttatcaa caatcagtac taccagacat ctgctgcgtt caaatcggat 120

atcgaagaga tcgaccaact aagaaatgat gtcctatcaa tagaaccaaa caatgatgga 180

cttgcattgc tcaagagata ctatgtacag ttagccagca ttagccaaaa actccctgat 240 Page 77

37324PCT_CRF_sequencelisting 19 Apr 2022

tattttatgg agtatccctg gtttggaaca ttaggatacc aagtaactgg ccccgtagct 300

ctaaaatccc tctatttcga aagaatcaat atagcgtaca acatcgcagc gacgtattca 360

atcataggtt taaacgagcc cagagctaca ggagaaggct tgaaaaaatc atgcatttat 420

tttcagtata gtagtggggc attcgaaagt gtactgaagc tagtggagca aaaaccgaaa 480 2022202534

gagctgacac ttcccattga tcttagtgtt aacattatga aaaccctggc taaactcatg 540

ctggctcagg cccaggaatg tttttggcaa aaggctgttt ctaacacttt aaaagataac 600

gttattgcaa ggttggcctt tcaagtatct caattttacg atgaagctct gtctatggct 660

tacaagtgcg atattttaaa gtctgaatgg atagaacata tgagttgcaa gaagctgcat 720

tttaaggctg cggcccaatt tagacttgct tgtgtggcag tcgctgcttc tagacatgga 780

gaggaaatag caagattaag gattgcaaat accatttgcg aaacagcatc tagagaagcc 840

aagtatcacc ttccctctgt atcttccgat ttggagagtc tttcgaagat aatcaaagac 900

tctttaagaa gaagtgaacg tgataatgat ctaatatatc tgcaggaagt tcctaatgaa 960

tcagatcttc ctccaattgt tgcagcatct atggttgaac ctaagccaat agttgagtta 1020

aattcagctg aatgtgcgaa agatacaaag aaatacggca aaatcctttt ccatgatctt 1080

atgccatact tagtgattga aattgcacag gcatttagag agaggcagga ttcttatgtt 1140

gtaaagcata tcaaggagcc catggagatg ctgacaaaga ttcttcacac aatccttgct 1200

gaaaatggac ttccggcgtt gatagatacc atacaaaggc ctcaaagatt gccaaccaac 1260

atccttgaac attgtcaaat actcaatgaa aggggtggca tggacaaact taaggtattt 1320

ttcgaagata tcagcaagct aagacacaaa agtgagcaag ttctccaaaa ctgtgtcgaa 1380

ttgctacaaa tggaagagtc cgaaaatgag gaaatgagaa ggaagcatgg atcacagagg 1440

tggaattttg ctgactctag ggaggcatca gcagatgtca ggaaaagtgt acaggcacta 1500

gagggctatt tgaaacaggc ccatgatggt gatcaagtga tctggaatga cttcgaacaa 1560

ttgaagccac tactaagcat gatgagtgct cctaattcaa ctaaattact ggaagaattt 1620

gtaccaaatt caaaattcgt cagacttcct ccagaattga accgaatcgt taacgaatta 1680

agagctgatg ttaatcaggt caaaaagctc gcatcgcaaa gggaaacttt tattaataca 1740

gttaaagtaa aaagcaccga cctgtccata ttgcccttgg tagtttccca ttataagaaa 1800 Page 78

37324PCT_CRF_sequencelisting 19 Apr 2022

ttacaacaaa acaacattaa tacgatcacg acggaattgt tcgaagaagt gttcagacga 1860

caggttagca acttcgattc tgatatcaga tttgttcaaa aacacaggga caaccaaatc 1920

gagttagaga agcatattaa atctttggtc caacaattca atcagcttag agggaatata 1980

gatgcctcgc aagaacgcca aaatgcactt cagttgttgg acgatgccta taacggatac 2040 2022202534

cttgatttgg taaacaacct cacacaggga cttagttttt acaatgattt cactggaaag 2100

gcaaatgatg tctatttgag atgtcaagaa ttctacaact ttcgtaaaca agaagccatg 2160

aagctggagc aggaaatata tgctgtattt gaacaaggta aatctcctca gaaaaaacaa 2220

ctagaagatc aggtttcaga tcaaccaaaa agtgaagtca agtcttcaaa gggttattct 2280

aatgagctgt ggaaccccga cgttggaatt aaatttggct ag 2322

<210> 66 <211> 960 <212> DNA <213> Pichia pastoris

<400> 66 atggtggcct ctcttcacat tgtcaatccg aatttggcct ccgctttcag tttgcctccc 60

aggtcaaaca ctttgagcgt ttccatacac gcttcggctt tgttacagat cctggaatca 120

agttacttcg accagaataa gaatggtcgt atcataggaa ccctcctagg ttctaggtct 180

gaagagacaa cggaggttca agtcaaagac tctttcatag tttcccacac ggaggacgga 240

gacgagttta ccattgattc ttctcaacgt gaatttgtcg ccatccacaa gaagtctagc 300

ccaagagact cagtcgtagg atggttttcc attaactcta aggtcgacag ctttatcgga 360

ctggtccatg actttttctc aaagggtcca gatagcacac acccgtaccc tgccatatat 420

ttgagtatcc agttatgtga cgagagcgga tccttcgtag agccagtttt caaggcgtac 480

gttgcctccc cagtgggatg ttatggagct ctggcaagtc acttagacct tgaaaaagct 540

ggctcttttg tcttctctga agtcccaacc aaggtcatat actctgctaa cgaaaaaagt 600

ctgctggctc atttcaagaa caacgttgtg gaacccaaag ttccaatacc acaaaacgac 660

acaaatcaac taatttcaca actcaacaaa ctcgacgttt ccattgacca gttaatagac 720

tacgttgaca aagtcatttc aggatctctg gatagaaatg atgtgaagaa tgatgagatt 780

Page 79

37324PCT_CRF_sequencelisting 19 Apr 2022

ggccgtttcc tgttgaccaa cttagtttcc cttccaactt ctccttcaaa ggaagagctt 840

tcatcttcca taagctctca tatccaggac tcactgatga tcgactactt ggcctccgcc 900

gtgaaaactc aattagatgt tagctccaaa ttaatgaacc tggtacaaga tgataaatag 960

<210> 67 <211> 599 2022202534

<212> PRT <213> Pichia pastoris

<400> 67 Met Leu Lys Asp Gln Phe Leu Leu Trp Val Ala Leu Ile Ala Ser Val 1 5 10 15

Pro Val Ser Gly Val Met Ala Ala Pro Ser Glu Ser Gly His Asn Thr 20 25 30

Val Glu Lys Arg Asp Ala Lys Asn Val Val Gly Val Gln Gln Leu Asp 35 40 45

Phe Ser Val Leu Arg Gly Asp Ser Phe Glu Ser Ala Ser Ser Glu Asn 50 55 60

Val Pro Arg Leu Val Arg Arg Asp Asp Thr Leu Glu Ala Glu Leu Ile 65 70 75 80

Asn Gln Gln Ser Phe Tyr Leu Ser Arg Leu Lys Val Gly Ser His Gln 85 90 95

Ala Asp Ile Gly Ile Leu Val Asp Thr Gly Ser Ser Asp Leu Trp Val 100 105 110

Met Asp Ser Val Asn Pro Tyr Cys Ser Ser Arg Ser Arg Val Lys Arg 115 120 125

Asp Ile His Asp Glu Lys Ile Ala Glu Trp Asp Pro Ile Asn Leu Lys 130 135 140

Lys Asn Glu Thr Ser Gln Asn Lys Asn Phe Trp Asp Trp Leu Val Gly 145 150 155 160

Page 80

37324PCT_CRF_sequencelisting 19 Apr 2022

Thr Ser Thr Ser Ser Pro Ser Thr Ala Thr Ala Thr Gly Ser Gly Ser 165 170 175

Gly Ser Gly Ser Gly Ser Gly Ser Gly Ser Ala Ala Thr Ala Val Ser 180 185 190 2022202534

Val Ser Ser Ala Gln Ala Thr Leu Asp Cys Ser Thr Tyr Gly Thr Phe 195 200 205

Asp His Ala Asp Ser Ser Thr Phe His Asp Asn Asn Thr Asp Phe Phe 210 215 220

Ile Ser Tyr Ala Asp Thr Thr Phe Ala Ser Gly Ile Trp Gly Tyr Asp 225 230 235 240

Asp Val Ile Ile Asp Gly Ile Glu Val Lys Glu Leu Ser Phe Ala Val 245 250 255

Ala Asp Met Thr Asn Ser Ser Ile Gly Val Leu Gly Ile Gly Leu Lys 260 265 270

Gly Leu Glu Ser Thr Tyr Ala Ser Ala Ser Ser Val Ser Glu Met Tyr 275 280 285

Gln Tyr Asp Asn Leu Pro Ala Lys Met Val Thr Asp Gly Leu Ile Asn 290 295 300

Lys Asn Ala Tyr Ser Leu Tyr Leu Asn Ser Lys Asp Ala Ser Ser Gly 305 310 315 320

Ser Ile Leu Phe Gly Gly Val Asp His Glu Lys Tyr Ser Gly Gln Leu 325 330 335

Leu Thr Val Pro Val Ile Asn Thr Leu Ala Ser Ser Gly Tyr Arg Glu 340 345 350

Ala Ile Arg Leu Gln Ile Thr Leu Asn Gly Ile Asp Val Lys Lys Gly 355 360 365

Page 81

37324PCT_CRF_sequencelisting 19 Apr 2022

Ser Asp Gln Gly Thr Leu Leu Gln Gly Arg Phe Ala Ala Leu Leu Asp 370 375 380

Ser Gly Ala Thr Leu Thr Tyr Ala Pro Ser Ser Val Leu Asn Ser Ile 385 390 395 400 2022202534

Gly Arg Asn Leu Gly Gly Ser Tyr Asp Ser Ser Arg Gln Ala Tyr Thr 405 410 415

Ile Arg Cys Val Ser Ala Ser Asp Thr Thr Ser Leu Val Phe Asn Phe 420 425 430

Gly Gly Ala Thr Val Glu Val Ser Leu Tyr Asp Leu Gln Ile Ala Thr 435 440 445

Tyr Tyr Thr Gly Gly Ser Ala Thr Gln Cys Leu Ile Gly Ile Phe Ser 450 455 460

Ser Gly Ser Asp Glu Phe Val Leu Gly Asp Thr Phe Leu Arg Ser Ala 465 470 475 480

Tyr Val Val Tyr Asp Leu Asp Gly Leu Glu Val Ser Leu Ala Gln Ala 485 490 495

Asn Phe Asn Glu Thr Asp Ser Asp Val Glu Ala Ile Thr Ser Ser Val 500 505 510

Pro Ser Ala Thr Arg Ala Ser Gly Tyr Ser Ser Thr Trp Ser Gly Ser 515 520 525

Ala Ser Gly Thr Val Tyr Thr Ser Val Gln Met Glu Ser Gly Ala Ala 530 535 540

Ser Ser Ser Asn Ser Ser Gly Ser Asn Met Gly Ser Ser Ser Ser Ser 545 550 555 560

Ser Ser Ser Ser Ser Ser Thr Ser Ser Gly Asp Glu Glu Gly Gly Ser 565 570 575

Page 82

37324PCT_CRF_sequencelisting 19 Apr 2022

Ser Ala Asn Arg Val Pro Phe Ser Tyr Leu Ser Leu Cys Leu Val Val 580 585 590

Ile Leu Gly Val Cys Ile Val 595 2022202534

<210> 68 <211> 562 <212> PRT <213> Pichia pastoris

<400> 68 Met Ile Ile Asn His Leu Val Leu Thr Ala Leu Ser Ile Ala Leu Ala 1 5 10 15

Asn Asp Tyr Glu Ser Leu Asp Leu Arg His Ile Gly Val Leu Tyr Thr 20 25 30

Ala Glu Ile Gln Ile Gly Ser Asp Glu Thr Glu Ile Glu Val Ile Val 35 40 45

Asp Thr Gly Ser Ala Asp Leu Trp Val Ile Asp Ser Asp Ala Ala Val 50 55 60

Cys Glu Leu Ser Tyr Asp Glu Ile Glu Ala Asn Ser Phe Ser Ser Ala 65 70 75 80

Ser Ala Lys Phe Met Asp Lys Ile Ala Pro Pro Ser Gln Glu Leu Leu 85 90 95

Asp Gly Leu Ser Glu Phe Gly Phe Ala Leu Asp Gly Glu Ile Ser Gln 100 105 110

Tyr Leu Ala Asp Lys Ser Gly Arg Val Ser Lys Arg Glu Glu Asn Gln 115 120 125

Gln Asp Phe Asn Ile Asn Arg Asp Glu Pro Val Cys Glu Gln Phe Gly 130 135 140

Ser Phe Asp Ser Ser Ser Ser Asp Thr Phe Gln Ser Asn Asn Ser Ala Page 83

37324PCT_CRF_sequencelisting 19 Apr 2022

145 150 155 160

Phe Gly Ile Ala Tyr Leu Asp Gly Thr Thr Ala Asn Gly Thr Trp Val 165 170 175

Arg Asp Thr Val Arg Ile Gly Asp Phe Ala Ile Ser Gln Gln Ser Phe 180 185 190 2022202534

Ala Leu Val Asn Ile Thr Asp Asn Tyr Met Gly Ile Leu Gly Leu Gly 195 200 205

Pro Ala Thr Gln Gln Thr Thr Asn Ser Asn Pro Ile Ala Ala Asn Arg 210 215 220

Phe Thr Tyr Asp Gly Val Val Asp Ser Leu Arg Ser Gln Gly Phe Ile 225 230 235 240

Asn Ser Ala Ser Phe Ser Val Tyr Leu Ser Pro Asp Glu Asp Asn Glu 245 250 255

His Asp Glu Phe Ser Asp Gly Glu Ile Leu Phe Gly Ala Ile Asp Arg 260 265 270

Ala Lys Ile Asp Gly Pro Phe Arg Leu Phe Pro Tyr Val Asn Pro Tyr 275 280 285

Lys Pro Val Tyr Pro Asp Gln Tyr Thr Ser Tyr Val Thr Val Ser Thr 290 295 300

Ile Ala Val Ser Ser Ser Asp Glu Thr Leu Ile Ile Glu Arg Arg Pro 305 310 315 320

Arg Leu Ala Leu Ile Asp Thr Gly Ala Thr Phe Ser Tyr Leu Pro Thr 325 330 335

Tyr Pro Leu Ile Arg Leu Ala Phe Ser Ile His Gly Gly Phe Glu Tyr 340 345 350

Val Ser Gln Leu Gly Leu Phe Val Ile Arg Thr Ser Ser Leu Ser Val Page 84

37324PCT_CRF_sequencelisting 19 Apr 2022

355 360 365

Ala Arg Asn Lys Val Ile Glu Phe Lys Phe Gly Glu Asp Val Val Ile 370 375 380

Gln Ser Pro Val Ser Asp His Leu Leu Asp Val Ser Gly Leu Phe Thr 385 390 395 400 2022202534

Asp Gly Gln Gln Tyr Ser Ala Leu Thr Val Arg Glu Ser Leu Asp Gly 405 410 415

Leu Ser Ile Leu Gly Asp Thr Phe Ile Lys Ser Ala Tyr Leu Phe Phe 420 425 430

Asp Asn Glu Asn Ser Gln Leu Gly Ile Gly Gln Ile Asn Val Thr Asp 435 440 445

Asp Glu Asp Ile Glu Val Val Gly Asp Phe Thr Ile Glu Arg Asp Pro 450 455 460

Ala Tyr Ser Ser Thr Trp Ser Ser Asp Leu Pro His Glu Thr Pro Thr 465 470 475 480

Arg Ala Leu Ser Thr Ala Ser Gly Gly Gly Leu Gly Thr Gly Ile Asn 485 490 495

Thr Ala Thr Ser Arg Ala Ser Ser Arg Ser Thr Ser Gly Ser Thr Ser 500 505 510

Arg Thr Ser Ser Thr Ser Gly Ser Ala Ser Gly Thr Ser Ser Gly Ala 515 520 525

Ser Ser Ala Thr Gln Asn Asp Glu Thr Ser Thr Asp Leu Gly Ala Pro 530 535 540

Ala Ala Ser Leu Ser Ala Thr Pro Cys Leu Phe Ala Ile Leu Leu Leu 545 550 555 560

Met Leu Page 85

37324PCT_CRF_sequencelisting 19 Apr 2022

<210> 69 <211> 207 <212> PRT <213> Pichia pastoris

<400> 69 2022202534

Met Val Ala Ser His Val Asn Asn Ala Ser Ala Ser Arg Ser Asn Thr 1 5 10 15

Ser Val Ser His Ala Ser Ala Ser Ser Tyr Asp Asn Lys Asn Gly Arg 20 25 30

Gly Thr Gly Ser Arg Ser Thr Thr Val Val Lys Asp Ser Val Ser His 35 40 45

Thr Asp Gly Asp Thr Asp Ser Ser Arg Val Ala His Lys Lys Ser Ser 50 55 60

Arg Asp Ser Val Val Gly Trp Ser Asn Ser Lys Val Asp Ser Gly Val 65 70 75 80

His Asp Ser Lys Gly Asp Ser Thr His Tyr Ala Tyr Ser Cys Asp Ser 85 90 95

Gly Ser Val Val Lys Ala Tyr Val Ala Ser Val Gly Cys Tyr Gly Ala 100 105 110

Ala Ser His Asp Lys Ala Gly Ser Val Ser Val Thr Lys Val Tyr Ser 115 120 125

Ala Asn Lys Ser Ala His Lys Asn Asn Val Val Lys Val Asn Asp Thr 130 135 140

Asn Ser Asn Lys Asp Val Ser Asp Asp Tyr Val Asp Lys Val Ser Gly 145 150 155 160

Ser Asp Arg Asn Asp Val Lys Asn Asp Gly Arg Thr Asn Val Ser Thr 165 170 175

Page 86

37324PCT_CRF_sequencelisting 19 Apr 2022

Ser Ser Lys Ser Ser Ser Ser Ser His Asp Ser Met Asp Tyr Ala Ser 180 185 190

Ala Val Lys Thr Asp Val Ser Ser Lys Met Asn Val Asp Asp Lys 195 200 205 2022202534

<210> 70 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 70 acctattgtt taccttcctg 20

<210> 71 <211> 40 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 71 gaattctctc acttaatctt tagctcccat gctcatcttg 40

<210> 72 <211> 40 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 72 gcggccgcaa gaagttgatt gtttatttgt aggcggtgcc 40

<210> 73 <211> 20 <212> DNA <213> Artificial Sequence Page 87

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 73 gggctatccg ccttatcttg 20 2022202534

<210> 74 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 74 aataacttca tgactgcatt 20

<210> 75 <211> 40 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 75 gaattctctc acttaatctt agtttaaata atatggagat 40

<210> 76 <211> 40 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 76 gcggccgcaa gaagttgatt attggagaaa aggaatacac 40

<210> 77 <211> 20 <212> DNA <213> Artificial Sequence Page 88

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 77 ggcatctccg tctggtgcag 20 2022202534

<210> 78 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 78 caaggttcga aactgcagct 20

<210> 79 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 79 ctcacttaat cttctgtact ctgaagagag agcaaaccaa tggcaa 46

<210> 80 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 80 agaagttgat tgagactttc aacgagggtc ctttggcaat cattggt 47

<210> 81 <211> 20 <212> DNA <213> Artificial Sequence Page 89

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 81 accccaggac caggtatttc 20 2022202534

<210> 82 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 82 tactacaggc tggctgttcc 20

<210> 83 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 83 ctcacttaat cttctgtact ctgaagaagt ccaactgttg aacgcc 46

<210> 84 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 84 agaagttgat tgagactttc aacgagggtc cccttcagct accttt 46

<210> 85 <211> 20 <212> DNA <213> Artificial Sequence Page 90

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 85 tccctgctaa gccctaatcg 20 2022202534

<210> 86 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 86 aagttgtatg gccgtcctca 20

<210> 87 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 87 ctcacttaat cttctgtact ctgaagtgag tcttggttgt gtcggt 46

<210> 88 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 88 agaagttgat tgagactttc aacgaggcct cctgtttgat cggttc 46

<210> 89 <211> 20 <212> DNA <213> Artificial Sequence Page 91

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 89 gtgccatggt gacgttacag 20 2022202534

<210> 90 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 90 cggagttata ggggacgctt 20

<210> 91 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 91 ctcacttaat cttctgtact ctgaagcgtc acatcatagc cgttctc 47

<210> 92 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 92 agaagttgat tgagactttc aacgagcgtc aaaagtggtc gtggac 46

<210> 93 <211> 20 <212> DNA <213> Artificial Sequence Page 92

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 93 tggcccagtt acacggaata 20 2022202534

<210> 94 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 94 gtcgatcgtt ggtgtgtgac 20

<210> 95 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 95 ctcacttaat cttctgtact ctgaaggagc cgactttgac atcgac 46

<210> 96 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 96 agaagttgat tgagactttc aacgagagcg aagagactgg ttccaa 46

<210> 97 <211> 20 <212> DNA <213> Artificial Sequence Page 93

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 97 agctgttcta accgtcctca 20 2022202534

<210> 98 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 98 cttggaatat ctgtgggcgc 20

<210> 99 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 99 ctcacttaat cttctgtact ctgaagtcat gaccagcagt tgttca 46

<210> 100 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 100 agaagttgat tgagactttc aacgagatgc tgcaggaagg aacact 46

<210> 101 <211> 20 <212> DNA <213> Artificial Sequence Page 94

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 101 caaactctgc acctccaagc 20 2022202534

<210> 102 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 102 ctctgattgc acgagaaggc 20

<210> 103 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 103 ctcacttaat cttctgtact ctgaagtgaa aggcgattgg agttgc 46

<210> 104 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 104 agaagttgat tgagactttc aacgagctgg ctctgcttct ggtact 46

<210> 105 <211> 20 <212> DNA <213> Artificial Sequence Page 95

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 105 gatgttgagg cgggcataag 20 2022202534

<210> 106 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 106 tttcaacggg gttctacgga 20

<210> 107 <211> 48 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 107 ctcacttaat cttctgtact ctgaaggtgg tagtatgtgt gttggtgt 48

<210> 108 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 108 agaagttgat tgagactttc aacgagctgc gctttcaagt actgca 46

<210> 109 <211> 20 <212> DNA <213> Artificial Sequence Page 96

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 109 tgtcttcctc gtcttcctcg 20 2022202534

<210> 110 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 110 cgggcaataa tcagtggagc 20

<210> 111 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 111 ctcacttaat cttctgtact ctgaagcgtt ggaggtaatg catggg 46

<210> 112 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 112 agaagttgat tgagactttc aacgagggcg gaccgtgtat tagaga 46

<210> 113 <211> 20 <212> DNA <213> Artificial Sequence Page 97

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 113 tcagagaagc cagtggaagg 20 2022202534

<210> 114 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 114 ttcctcggcc tctttatgct 20

<210> 115 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 115 ctcacttaat cttctgtact ctgaagcaac gtggctaact ccttgg 46

<210> 116 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 116 agaagttgat tgagactttc aacgaggttg tcgacggcat tgaaga 46

<210> 117 <211> 20 <212> DNA <213> Artificial Sequence Page 98

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 117 tcggttcaaa gcccctaagt 20 2022202534

<210> 118 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 118 aggtgtgaaa tgcgctgatc 20

<210> 119 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 119 ctcacttaat cttctgtact ctgaagaaac caacaacgcc tggtac 46

<210> 120 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 120 agaagttgat tgagactttc aacgagtcac aggctgaagg atcgaa 46

<210> 121 <211> 20 <212> DNA <213> Artificial Sequence Page 99

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 121 ccatggtgtg ttttccggtt 20 2022202534

<210> 122 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 122 tgagggacaa agtaatgggg t 21

<210> 123 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 123 ctcacttaat cttctgtact ctgaagaccg aagtcatggt tggaaa 46

<210> 124 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 124 agaagttgat tgagactttc aacgagctac cgcagacaac ccattc 46

<210> 125 <211> 20 <212> DNA <213> Artificial Sequence Page 100

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 125 cgctccctca tcgagtactt 20 2022202534

<210> 126 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 126 cagacatcgt ggaaactgcc 20

<210> 127 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 127 ctcacttaat cttctgtact ctgaagtatc tgcttcgatc cctgca 46

<210> 128 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 128 agaagttgat tgagactttc aacgagttct cccgtccagt tagcag 46

<210> 129 <211> 20 <212> DNA <213> Artificial Sequence Page 101

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 129 atttcagaag ctccgcatcc 20 2022202534

<210> 130 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 130 acaaaagcac gcgattgaga 20

<210> 131 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 131 ctcacttaat cttctgtact ctgaagacac tcacggttgt ttgcaa 46

<210> 132 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 132 agaagttgat tgagactttc aacgagaacc ccaacaagcg gctata 46

<210> 133 <211> 20 <212> DNA <213> Artificial Sequence Page 102

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 133 acccggatct gctagtgaag 20 2022202534

<210> 134 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 134 cgtatgctcg tgtgactgtg 20

<210> 135 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 135 ctcacttaat cttctgtact ctgaagttcc tatgcctggc gatgat 46

<210> 136 <211> 49 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 136 agaagttgat tgagactttc aacgagaggg agtcttgtat agttgagca 49

<210> 137 <211> 20 <212> DNA <213> Artificial Sequence Page 103

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 137 agcaggggta ttttcacgga 20 2022202534

<210> 138 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 138 agcatgattg tgttgggtgg 20

<210> 139 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 139 ctcacttaat cttctgtact ctgaagaatc cgatactgta gccccg 46

<210> 140 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 140 agaagttgat tgagactttc aacgaggcaa agaaaactgg ccacac 46

<210> 141 <211> 20 <212> DNA <213> Artificial Sequence Page 104

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 141 ggaaggccct attcacgact 20 2022202534

<210> 142 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 142 caccatttcc ctgctgtgtc 20

<210> 143 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 143 ctcacttaat cttctgtact ctgaagtcaa taccgaagac tccgca 46

<210> 144 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 144 agaagttgat tgagactttc aacgagggga ggtattcagg aggcat 46

<210> 145 <211> 21 <212> DNA <213> Artificial Sequence Page 105

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 145 gctcgatcag atattgtccg c 21 2022202534

<210> 146 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 146 agcagctctc caatcagtgt 20

<210> 147 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 147 ctcacttaat cttctgtact ctgaagctgg aattgtgatc ccgctg 46

<210> 148 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 148 agaagttgat tgagactttc aacgagtttt gaagcaagcc tacccc 46

<210> 149 <211> 20 <212> DNA <213> Artificial Sequence Page 106

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 149 caggatccag ccgctaaaac 20 2022202534

<210> 150 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 150 tgaacaagca gccacatcac 20

<210> 151 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 151 ctcacttaat cttctgtact ctgaagtgag ggccattctg acatact 47

<210> 152 <211> 48 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 152 agaagttgat tgagactttc aacgaggtga ggtatttaac tgcacgag 48

<210> 153 <211> 20 <212> DNA <213> Artificial Sequence Page 107

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 153 tcgcctacat agtctgcaca 20 2022202534

<210> 154 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 154 acctcatgcc atgtctgtca 20

<210> 155 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 155 ctcacttaat cttctgtact ctgaagttga ctgccgcttc aaagtc 46

<210> 156 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 156 agaagttgat tgagactttc aacgagccgc cagagaattt gtgctt 46

<210> 157 <211> 20 <212> DNA <213> Artificial Sequence Page 108

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 157 tagaggtgaa cgtttggcct 20 2022202534

<210> 158 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 158 aatccatcac ctccacccag 20

<210> 159 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 159 ctcacttaat cttctgtact ctgaaggctg ctggagtaaa aggtcc 46

<210> 160 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 160 agaagttgat tgagactttc aacgagcaag cagcaaccat ctacgg 46

<210> 161 <211> 20 <212> DNA <213> Artificial Sequence Page 109

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 161 aacctcatcc actgtcagca 20 2022202534

<210> 162 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 162 ggaagacaaa gttcgctccg 20

<210> 163 <211> 48 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 163 ctcacttaat cttctgtact ctgaagtcat agttgagagc ctccttgt 48

<210> 164 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 164 agaagttgat tgagactttc aacgagacaa tgcactagga cgggat 46

<210> 165 <211> 20 <212> DNA <213> Artificial Sequence Page 110

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 165 cttgaatcag gcgacgtacc 20 2022202534

<210> 166 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 166 cccagctctc tttcactcca 20

<210> 167 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 167 ctcacttaat cttctgtact ctgaagttga agagcagcag agtcga 46

<210> 168 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 168 agaagttgat tgagactttc aacgagttaa ttgcccacag tgtcgc 46

<210> 169 <211> 20 <212> DNA <213> Artificial Sequence Page 111

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 169 accttccaca gtcgacgaat 20 2022202534

<210> 170 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 170 acaaacagtc aaatgcacgg a 21

<210> 171 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 171 ctcacttaat cttctgtact ctgaagtcct tccacctttc caacgt 46

<210> 172 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 172 agaagttgat tgagactttc aacgaggggg tagagaagtt agggagg 47

<210> 173 <211> 20 <212> DNA <213> Artificial Sequence Page 112

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 173 ggaactacaa ctggaggcct 20 2022202534

<210> 174 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 174 tagtgccggt tccatggatt 20

<210> 175 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 175 ctcacttaat cttctgtact ctgaagggtc tatgggttga tgcgga 46

<210> 176 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 176 agaagttgat tgagactttc aacgagatgt gttgctcgct ctaggt 46

<210> 177 <211> 20 <212> DNA <213> Artificial Sequence Page 113

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 177 cgacaaacac accaaggtcc 20 2022202534

<210> 178 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 178 gttgttggag tgagcgatgg 20

<210> 179 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 179 ctcacttaat cttctgtact ctgaagcctc cgttgatact cccgat 46

<210> 180 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 180 agaagttgat tgagactttc aacgagtgca ttcaaggctg gcaaat 46

<210> 181 <211> 20 <212> DNA <213> Artificial Sequence Page 114

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 181 gcatatggag tggtgtgcag 20 2022202534

<210> 182 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 182 cgggtagcat tgaacgtacg 20

<210> 183 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 183 ctcacttaat cttctgtact ctgaagatgc tacggtaaac acccca 46

<210> 184 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 184 agaagttgat tgagactttc aacgagactg gagaaagctt ggtcga 46

<210> 185 <211> 20 <212> DNA <213> Artificial Sequence Page 115

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 185 aggcaccaga agaaagagct 20 2022202534

<210> 186 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 186 ggacacgttt ggagcttctt 20

<210> 187 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 187 ctcacttaat cttctgtact ctgaaggccc accaattcag caactt 46

<210> 188 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 188 agaagttgat tgagactttc aacgaggatg ctggtcacat ggttcc 46

<210> 189 <211> 20 <212> DNA <213> Artificial Sequence Page 116

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 189 aaccgccaat agtttcagcc 20 2022202534

<210> 190 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 190 ggatgagaaa gcggcttctg 20

<210> 191 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 191 ctcacttaat cttctgtact ctgaaggtgc caaaagtctg atccgg 46

<210> 192 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 192 agaagttgat tgagactttc aacgagtgcc acttcgttct ttgacg 46

<210> 193 <211> 20 <212> DNA <213> Artificial Sequence Page 117

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 193 acggatcagt gatggcgtat 20 2022202534

<210> 194 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 194 atgggatctg gacgacgttt 20

<210> 195 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 195 ctcacttaat cttctgtact ctgaagagct ggatcacaaa cattcgg 47

<210> 196 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 196 agaagttgat tgagactttc aacgagcttt gagtgttggt ccctgc 46

<210> 197 <211> 20 <212> DNA <213> Artificial Sequence Page 118

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 197 cggctaccaa gtcagacctt 20 2022202534

<210> 198 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 198 gttgcccatt acgtcctgtg 20

<210> 199 <211> 49 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 199 ctcacttaat cttctgtact ctgaagcctt tgatctttgg tgcatcttg 49

<210> 200 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 200 agaagttgat tgagactttc aacgagcact acagctggga acgaga 46

<210> 201 <211> 20 <212> DNA <213> Artificial Sequence Page 119

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 201 acgggttgga aaagttgagc 20 2022202534

<210> 202 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 202 agtggggttg gagattggag 20

<210> 203 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 203 ctcacttaat cttctgtact ctgaagacga ttccagcata gcctgt 46

<210> 204 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 204 agaagttgat tgagactttc aacgagctgg tagccgcaaa acttca 46

<210> 205 <211> 20 <212> DNA <213> Artificial Sequence Page 120

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 205 gcgttgaatc ctcctcgttc 20 2022202534

<210> 206 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 206 ctgtggggtc tgaacatcct 20

<210> 207 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 207 ctcacttaat cttctgtact ctgaagagct gctagggttc attgagt 47

<210> 208 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 208 agaagttgat tgagactttc aacgagctcc cttgggtacg tcaact 46

<210> 209 <211> 20 <212> DNA <213> Artificial Sequence Page 121

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 209 tggcagtctt cacatgtcct 20 2022202534

<210> 210 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 210 agctggtcaa gtctggtacc 20

<210> 211 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 211 ctcacttaat cttctgtact ctgaaggagg tctagtgtgt gaggct 46

<210> 212 <211> 49 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 212 agaagttgat tgagactttc aacgagagaa ggtataggga atatgcggt 49

<210> 213 <211> 20 <212> DNA <213> Artificial Sequence Page 122

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 213 tagccacaac cctgatgacg 20 2022202534

<210> 214 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 214 tacactggga cgcagatgtt 20

<210> 215 <211> 48 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 215 ctcacttaat cttctgtact ctgaagtgct caaactctgt atccgttg 48

<210> 216 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 216 agaagttgat tgagactttc aacgagcttt caaggccgca atgcta 46

<210> 217 <211> 20 <212> DNA <213> Artificial Sequence Page 123

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 217 cttcctttgc agttggtggt 20 2022202534

<210> 218 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 218 gggtctttgg ctttggtgag 20

<210> 219 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 219 ctcacttaat cttctgtact ctgaagcgtc tctggaactc gtcgat 46

<210> 220 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 220 agaagttgat tgagactttc aacgagcccc aagtcaagga ggagtt 46

<210> 221 <211> 20 <212> DNA <213> Artificial Sequence Page 124

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 221 gagtccaatc acggccaatc 20 2022202534

<210> 222 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 222 tgcttcttcg gacagatcgt 20

<210> 223 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 223 ctcacttaat cttctgtact ctgaagtact gattgaaggg tcggca 46

<210> 224 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 224 agaagttgat tgagactttc aacgagttgt acggaccagg aagcat 46

<210> 225 <211> 20 <212> DNA <213> Artificial Sequence Page 125

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 225 ttcctctgcc tcttccttgg 20 2022202534

<210> 226 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 226 agcatgcaaa cacgaggtac 20

<210> 227 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 227 ctcacttaat cttctgtact ctgaagagag gaaaacgagc ttgggt 46

<210> 228 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 228 agaagttgat tgagactttc aacgagatca aggttgccag cgaatg 46

<210> 229 <211> 20 <212> DNA <213> Artificial Sequence Page 126

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 229 accctacaga accgcaatga 20 2022202534

<210> 230 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 230 acagcccaaa tagagacgca 20

<210> 231 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 231 ctcacttaat cttctgtact ctgaagagga gcccagtttt acgtca 46

<210> 232 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 232 agaagttgat tgagactttc aacgagtatc ccgcggtgaa gactac 46

<210> 233 <211> 20 <212> DNA <213> Artificial Sequence Page 127

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 233 gtgttgctaa gcctgtggac 20 2022202534

<210> 234 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 234 tcctcctttc gacgcttctt 20

<210> 235 <211> 49 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 235 ctcacttaat cttctgtact ctgaagacag ctgtgaatca tgaagtttt 49

<210> 236 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 236 agaagttgat tgagactttc aacgagattc tcactggcag aacgga 46

<210> 237 <211> 20 <212> DNA <213> Artificial Sequence Page 128

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 237 ttttcacgtt gaggccactg 20 2022202534

<210> 238 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 238 agctccgcag taacaggaat 20

<210> 239 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 239 ctcacttaat cttctgtact ctgaagtcaa agcaacttat ggcggt 46

<210> 240 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 240 agaagttgat tgagactttc aacgagctct tcgcagcacc agaaag 46

<210> 241 <211> 20 <212> DNA <213> Artificial Sequence Page 129

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 241 tcgttgttgc tggtgttctg 20 2022202534

<210> 242 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 242 agtttgaagg cacgttggtc 20

<210> 243 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 243 ctcacttaat cttctgtact ctgaagactc caacaggact ttgaggt 47

<210> 244 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 244 agaagttgat tgagactttc aacgagaaat gtggaagttg cagcgg 46

<210> 245 <211> 20 <212> DNA <213> Artificial Sequence Page 130

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 245 aggttgatcg ccgtcttgta 20 2022202534

<210> 246 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 246 tcttcatgag gtggtaggcg 20

<210> 247 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 247 ctcacttaat cttctgtact ctgaagagag ggcagatgac ataccg 46

<210> 248 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 248 agaagttgat tgagactttc aacgaggaga aactggaggt gctcgt 46

<210> 249 <211> 20 <212> DNA <213> Artificial Sequence Page 131

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 249 caaggcattc agttgaccgt 20 2022202534

<210> 250 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 250 accaacgagc cttacagaca 20

<210> 251 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 251 ctcacttaat cttctgtact ctgaagtttt gaccgtcagt gcatgg 46

<210> 252 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 252 agaagttgat tgagactttc aacgaggtcg gaggtgtgag aattga 46

<210> 253 <211> 20 <212> DNA <213> Artificial Sequence Page 132

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 253 tgggaactat gtggctcctc 20 2022202534

<210> 254 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 254 cgagctatca gtactcccgg 20

<210> 255 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 255 ctcacttaat cttctgtact ctgaagggtt ctcagctgtc cgagat 46

<210> 256 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 256 agaagttgat tgagactttc aacgagtagc attgcccatc acaacg 46

<210> 257 <211> 21 <212> DNA <213> Artificial Sequence Page 133

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 257 gtgggaagac tattgatgcg a 21 2022202534

<210> 258 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 258 gggaaatcgc tgaggtgtac 20

<210> 259 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 259 ctcacttaat cttctgtact ctgaagaggt catctggaag ctttgc 46

<210> 260 <211> 49 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 260 agaagttgat tgagactttc aacgagggtg gccaatggta ttactttga 49

<210> 261 <211> 20 <212> DNA <213> Artificial Sequence Page 134

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 261 ataagagccc cgatacaggc 20 2022202534

<210> 262 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 262 cttgacacac tttgctcctg a 21

<210> 263 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 263 ctcacttaat cttctgtact ctgaagagta gctgacctgt tgtgcc 46

<210> 264 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 264 agaagttgat tgagactttc aacgagggac accatatgat gcccga 46

<210> 265 <211> 20 <212> DNA <213> Artificial Sequence Page 135

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 265 cagatcaagt ccaagtccgc 20 2022202534

<210> 266 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 266 agagactttg cgagagtccc 20

<210> 267 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 267 ctcacttaat cttctgtact ctgaagtgca atatccaaac acgcca 46

<210> 268 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 268 agaagttgat tgagactttc aacgagactt ctggaatctt cgggca 46

<210> 269 <211> 20 <212> DNA <213> Artificial Sequence Page 136

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 269 ggatgtttgg gccattgtga 20 2022202534

<210> 270 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 270 caatctctcg cttcatcacg 20

<210> 271 <211> 49 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 271 ctcacttaat cttctgtact ctgaagtcgc tgttaaccat aattctttg 49

<210> 272 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 272 agaagttgat tgagactttc aacgaggcga gggttgagga gatttt 46

<210> 273 <211> 20 <212> DNA <213> Artificial Sequence Page 137

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 273 ggccatggca ctattttgtt 20 2022202534

<210> 274 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 274 acgtacttcc cgcccaataa 20

<210> 275 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 275 ctcacttaat cttctgtact ctgaagccca cctaaatttc gagtgca 47

<210> 276 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 276 agaagttgat tgagactttc aacgagacac tttcgcagct tttggt 46

<210> 277 <211> 20 <212> DNA <213> Artificial Sequence Page 138

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 277 tcctccttgc catgaagagg 20 2022202534

<210> 278 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 278 gcctgatgaa gatgatgccg 20

<210> 279 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 279 ctcacttaat cttctgtact ctgaagaggc tcagtcacct ctatga 46

<210> 280 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 280 agaagttgat tgagactttc aacgagtgat caagaacacc gtcgaag 47

<210> 281 <211> 20 <212> DNA <213> Artificial Sequence Page 139

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 281 tccctttgtt ggtcgtacga 20 2022202534

<210> 282 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 282 tggttcaact tgtagcgcat 20

<210> 283 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 283 ctcacttaat cttctgtact ctgaaggggc ttgctcaact tttgga 46

<210> 284 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 284 agaagttgat tgagactttc aacgagcgac aatctggtag cgcatc 46

<210> 285 <211> 20 <212> DNA <213> Artificial Sequence Page 140

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 285 atgctcgtac aaagacccca 20 2022202534

<210> 286 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 286 tgagatctcc aagtgcagca 20

<210> 287 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 287 ctcacttaat cttctgtact ctgaaggacg gtcgatttgg ctcatc 46

<210> 288 <211> 49 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 288 agaagttgat tgagactttc aacgagtgaa gaagctcaac actctgaac 49

<210> 289 <211> 20 <212> DNA <213> Artificial Sequence Page 141

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 289 tgattgacgg caccctgtat 20 2022202534

<210> 290 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 290 caataattca gctgcgccct 20

<210> 291 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 291 ctcacttaat cttctgtact ctgaagcctc tgtagctgct tgtcct 46

<210> 292 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 292 agaagttgat tgagactttc aacgagagga gtcagtcggt ccaaag 46

<210> 293 <211> 20 <212> DNA <213> Artificial Sequence Page 142

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 293 tgtgggctgg gatgtgtaat 20 2022202534

<210> 294 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 294 agcacggtca agtaaatcgc 20

<210> 295 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 295 ctcacttaat cttctgtact ctgaagtgct atcactgatt tgccca 46

<210> 296 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 296 agaagttgat tgagactttc aacgagggag attcccggca agtatc 46

<210> 297 <211> 20 <212> DNA <213> Artificial Sequence Page 143

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 297 ggctttctga ctacctgggt 20 2022202534

<210> 298 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 298 aaagggaaga agggtgcagt 20

<210> 299 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 299 ctcacttaat cttctgtact ctgaagaagg tcgactcggg aaacat 46

<210> 300 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 300 agaagttgat tgagactttc aacgagtggt atcccgactg ctttgt 46

<210> 301 <211> 20 <212> DNA <213> Artificial Sequence Page 144

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 301 tggaatggct cgagaatggt 20 2022202534

<210> 302 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 302 accaacaggc tgaacactag a 21

<210> 303 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 303 ctcacttaat cttctgtact ctgaagtcgt cagcagagaa ggtaca 46

<210> 304 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 304 agaagttgat tgagactttc aacgagacgg actccctaac gaacaa 46

<210> 305 <211> 20 <212> DNA <213> Artificial Sequence Page 145

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 305 tctgatggtt ggctttgctt 20 2022202534

<210> 306 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 306 cggtttgtgg cccatctatg 20

<210> 307 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 307 ctcacttaat cttctgtact ctgaagaaaa ccgacgcttg aactcc 46

<210> 308 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 308 agaagttgat tgagactttc aacgagaagt cttgaccgga agcaac 46

<210> 309 <211> 20 <212> DNA <213> Artificial Sequence Page 146

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 309 gggccttaac aaacaccaca 20 2022202534

<210> 310 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 310 tagaggcgga aaggaacgag 20

<210> 311 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 311 ctcacttaat cttctgtact ctgaagttgc caagggtgta caaagc 46

<210> 312 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 312 agaagttgat tgagactttc aacgagacca agttgttcga cgaaga 46

<210> 313 <211> 20 <212> DNA <213> Artificial Sequence Page 147

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 313 caacacatac caggcgaagg 20 2022202534

<210> 314 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 314 ccctcctccg ccatcattat 20

<210> 315 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 315 ctcacttaat cttctgtact ctgaagtagg agacaaccaa gccagc 46

<210> 316 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 316 agaagttgat tgagactttc aacgagggag tagaaaatgg tgcgtcc 47

<210> 317 <211> 20 <212> DNA <213> Artificial Sequence Page 148

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 317 aatggctcca aatcacaggc 20 2022202534

<210> 318 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 318 gctttgagga atgcgtgaag a 21

<210> 319 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 319 ctcacttaat cttctgtact ctgaaggtag tgagagtggc gcctta 46

<210> 320 <211> 47 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 320 agaagttgat tgagactttc aacgagtggg tacaacgtga ctctagg 47

<210> 321 <211> 20 <212> DNA <213> Artificial Sequence Page 149

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 321 acactcttaa ggctcgtcgt 20 2022202534

<210> 322 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 322 ctcctccact tcagtatccg t 21

<210> 323 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 323 ctcacttaat cttctgtact ctgaagttcc ttgaatttcc gccacc 46

<210> 324 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 324 agaagttgat tgagactttc aacgaggagc aggcaaggtt ggattc 46

<210> 325 <211> 20 <212> DNA <213> Artificial Sequence Page 150

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 325 ctgggcagca aataacggtt 20 2022202534

<210> 326 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 326 ccaaagttgg ctccgagtag 20

<210> 327 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 327 ctcacttaat cttctgtact ctgaagccta acggtatcgg ctttga 46

<210> 328 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 328 agaagttgat tgagactttc aacgagggca aaatcctttt ccatga 46

<210> 329 <211> 20 <212> DNA <213> Artificial Sequence Page 151

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 329 gaagaaggcc aagtgtgata 20 2022202534

<210> 330 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 330 gacgagacgc tgttcctttc 20

<210> 331 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 331 ctcacttaat cttctgtact ctgaagtgtg aagagaggcc accatt 46

<210> 332 <211> 46 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 332 agaagttgat tgagactttc aacgagtgat cgactacttg gcctcc 46

<210> 333 <211> 20 <212> DNA <213> Artificial Sequence Page 152

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 333 aacaacattc aagctgccgt 20 2022202534

<210> 334 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 334 atcggcaaag atgaagcgac 20

<210> 335 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 335 gctggacact tctgagctca 20

<210> 336 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 336 acttgtcagg acgatacgga 20

<210> 337 <211> 20 <212> DNA <213> Artificial Sequence Page 153

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 337 ccggtctccc tggaaataga 20 2022202534

<210> 338 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 338 gcgaggtcct tgtcaatgag 20

<210> 339 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 339 acaagaactc gggctccttt 20

<210> 340 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 340 ttgcagcgct ccataatgtc 20

<210> 341 <211> 20 <212> DNA <213> Artificial Sequence Page 154

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 341 gctgattctg agaacgctgg 20 2022202534

<210> 342 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 342 gccattcttc ggtgcagtag 20

<210> 343 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 343 tagagttgtc ccaaacggca 20

<210> 344 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 344 cgtggttctc gaggctctat 20

<210> 345 <211> 20 <212> DNA <213> Artificial Sequence Page 155

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 345 ggagttggaa cgtcgtagga 20 2022202534

<210> 346 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 346 agttgtccgt cattagccct 20

<210> 347 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 347 tgttcccttt cggctagaca 20

<210> 348 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 348 acggttgagg gcattacgta 20

<210> 349 <211> 20 <212> DNA <213> Artificial Sequence Page 156

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 349 ttgtcttcca ccccttcgtt 20 2022202534

<210> 350 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 350 ggttggcctt ggacattgtt 20

<210> 351 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 351 tgctcttcgg tactcatgct 20

<210> 352 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 352 tttggccatg ctgagctttt 20

<210> 353 <211> 20 <212> DNA <213> Artificial Sequence Page 157

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 353 aagcccgatc acttgcattt 20 2022202534

<210> 354 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 354 cacctaatgt ttggcacccc 20

<210> 355 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 355 atcccagact gacatcgcaa 20

<210> 356 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 356 ccgccagaaa ttcatgccat 20

<210> 357 <211> 20 <212> DNA <213> Artificial Sequence Page 158

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 357 tcgtttcact gtaccatgca 20 2022202534

<210> 358 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 358 accagtccgc attttcactg 20

<210> 359 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 359 gtggacagct gcaatcgtag 20

<210> 360 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 360 caactgggaa gcctgcattt 20

<210> 361 <211> 20 <212> DNA <213> Artificial Sequence Page 159

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 361 ccttgcatat ccgtttgcca 20 2022202534

<210> 362 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 362 ggaggttcag gagcaggaat 20

<210> 363 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 363 cggtttcatc tgttgcctcc 20

<210> 364 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 364 gtcgcccatg ttctttcgat 20

<210> 365 <211> 20 <212> DNA <213> Artificial Sequence Page 160

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 365 caaacaggct ggaaaccaca 20 2022202534

<210> 366 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 366 aatctccacg ttcagttgcg 20

<210> 367 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 367 tcatcccttg aaaaccccga 20

<210> 368 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 368 ttgtggaggg agattcaggc 20

<210> 369 <211> 20 <212> DNA <213> Artificial Sequence Page 161

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 369 aaggtaagga acgtgcttgc 20 2022202534

<210> 370 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 370 gttctactgt tcacgtgctc t 21

<210> 371 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 371 accggttaga atacatgctg c 21

<210> 372 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 372 cgaaaagaag ctggactccg 20

<210> 373 <211> 20 <212> DNA <213> Artificial Sequence Page 162

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 373 ttccatcgta cgaccagtgt 20 2022202534

<210> 374 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 374 agcgatgagg ccaacagtat 20

<210> 375 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 375 tgtccagccc aaaagactga 20

<210> 376 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 376 ctcctggggc tcgtactaag 20

<210> 377 <211> 20 <212> DNA <213> Artificial Sequence Page 163

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 377 cctcaataac gacggccttg 20 2022202534

<210> 378 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 378 ccttttcctg atcagtgggg 20

<210> 379 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 379 tgttggggaa tgaaacacga 20

<210> 380 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 380 gaaggacgag tagggttgct 20

<210> 381 <211> 20 <212> DNA <213> Artificial Sequence Page 164

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 381 tcctgatctg gctcgtttgt 20 2022202534

<210> 382 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 382 acctccaact cctgaaagca 20

<210> 383 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 383 cctcgagtct gggctttaca 20

<210> 384 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 384 ggagagatgc cagaccaagt 20

<210> 385 <211> 21 <212> DNA <213> Artificial Sequence Page 165

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 385 agcctgttct actgcatacg t 21 2022202534

<210> 386 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 386 ccatttcttg taccctgggc 20

<210> 387 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 387 gcagaaaagg cgcgaatttc 20

<210> 388 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 388 gggaaaggat gtggaccaac 20

<210> 389 <211> 20 <212> DNA <213> Artificial Sequence Page 166

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 389 tggccaagag tgtccaattg 20 2022202534

<210> 390 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 390 taacagatgg cgcacgtaga 20

<210> 391 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 391 ccttgcgttc ccaggtaaag 20

<210> 392 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 392 tgtggtatgg tttggggcta 20

<210> 393 <211> 20 <212> DNA <213> Artificial Sequence Page 167

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 393 actcccgttc ctccatgttc 20 2022202534

<210> 394 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 394 acggtacaaa aggcgtttca 20

<210> 395 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 395 agtcaaactc ggtggtaggt 20

<210> 396 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 396 cggttatcat gtgcctgctc 20

<210> 397 <211> 20 <212> DNA <213> Artificial Sequence Page 168

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 397 atgttgctgc tccgaaatcc 20 2022202534

<210> 398 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 398 gatctgctgg ccttgagagt 20

<210> 399 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 399 ctatgtcctg gtgtttgccg 20

<210> 400 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 400 gccaatgatg atctcgcagg 20

<210> 401 <211> 20 <212> DNA <213> Artificial Sequence Page 169

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 401 gcctttgata tgccgtcgtt 20 2022202534

<210> 402 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 402 tcgagtaatg cttcccacca 20

<210> 403 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 403 agctttcaca acagcgatcg 20

<210> 404 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 404 tgattgcttc tgggttgctg 20

<210> 405 <211> 20 <212> DNA <213> Artificial Sequence Page 170

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 405 caaaaccggc gtaaaatggc 20 2022202534

<210> 406 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 406 ttgtgctgca tctgtgtgag 20

<210> 407 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 407 agcctacaag tggttacagg t 21

<210> 408 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 408 ggaaaccgac cagcctaaag 20

<210> 409 <211> 20 <212> DNA <213> Artificial Sequence Page 171

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 409 agtcgcacca ggttatcaca 20 2022202534

<210> 410 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 410 ggaaagctgc ccagaaactc 20

<210> 411 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 411 tgagaggatt cgttgtggct 20

<210> 412 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 412 ctatgtcgaa gtagcggtgc 20

<210> 413 <211> 20 <212> DNA <213> Artificial Sequence Page 172

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 413 agagtggcac tgctatcgaa 20 2022202534

<210> 414 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 414 cgtacaaact tggcagctgt 20

<210> 415 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 415 gctgtgttgt aaattccggc 20

<210> 416 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 416 acaacccgga agacaactct 20

<210> 417 <211> 20 <212> DNA <213> Artificial Sequence Page 173

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 417 tgtcgttgcc ttcccgatat 20 2022202534

<210> 418 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 418 gaagatggga gagggtgctt 20

<210> 419 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 419 cttgttgacg acggtagcag 20

<210> 420 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 420 ccctagtctc gttcgaaggg 20

<210> 421 <211> 20 <212> DNA <213> Artificial Sequence Page 174

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 421 ggcacagcag gttttcgtat 20 2022202534

<210> 422 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 422 ggagattctg atgctacccc a 21

<210> 423 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 423 tggagccatc agatcaggac 20

<210> 424 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 424 cctgttcttg caagccttca 20

<210> 425 <211> 20 <212> DNA <213> Artificial Sequence Page 175

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 425 taagacatgc gaccaccaga 20 2022202534

<210> 426 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 426 catggccaat gtcgaactgt 20

<210> 427 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 427 agctggctga aaaggtgttg 20

<210> 428 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 428 ctcagtgttg gaaagcaccc 20

<210> 429 <211> 20 <212> DNA <213> Artificial Sequence Page 176

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 429 tagggaatct ttggtggcgt 20 2022202534

<210> 430 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 430 ggaacctaga gcgagcaaca 20

<210> 431 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 431 caggctctat tgtcgacgtg 20

<210> 432 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 432 ggaggtgatg acaatgccac 20

<210> 433 <211> 20 <212> DNA <213> Artificial Sequence Page 177

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 433 ctgtgaagct cctcctacgt 20 2022202534

<210> 434 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 434 ggacactgct ggacaagaga 20

<210> 435 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 435 tactgacgcc gaagagctag 20

<210> 436 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 436 ccgatcgcaa aatagtggca 20

<210> 437 <211> 20 <212> DNA <213> Artificial Sequence Page 178

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 437 gttgtggttg tatgcggtca 20 2022202534

<210> 438 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 438 caataactcc actggtgccg 20

<210> 439 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 439 tcgttatact ccagcgtgct 20

<210> 440 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 440 gggctcaaaa tctggaacca 20

<210> 441 <211> 20 <212> DNA <213> Artificial Sequence Page 179

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 441 caatgcagta ctcaccggtg 20 2022202534

<210> 442 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 442 aagctgacga ccccttagac 20

<210> 443 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 443 ctatcgtgtc tgggctgcta 20

<210> 444 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 444 aaggagattg ccgcaactct 20

<210> 445 <211> 20 <212> DNA <213> Artificial Sequence Page 180

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 445 gtggagtcag agtcgagagg 20 2022202534

<210> 446 <211> 21 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 446 cccagctttt atacggcttg g 21

<210> 447 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 447 cagcaaaagc tcgtgatcca 20

<210> 448 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 448 tgcgggtagt cgattgatgt 20

<210> 449 <211> 21 <212> DNA <213> Artificial Sequence Page 181

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 449 tcacgtatct cagcaacagg a 21 2022202534

<210> 450 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 450 ggacctagga aatacgccca 20

<210> 451 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 451 actccagttc cacaagtcca 20

<210> 452 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 452 actgccaacc gtttactcca 20

<210> 453 <211> 20 <212> DNA <213> Artificial Sequence Page 182

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 453 gcgcggaaga ttaaagtcgt 20 2022202534

<210> 454 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 454 ttggactcga tcgatgaggg 20

<210> 455 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 455 tgatgacttc caagatgcgc 20

<210> 456 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 456 tcacctggag caactgatgt 20

<210> 457 <211> 20 <212> DNA <213> Artificial Sequence Page 183

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 457 gtttggtacg cttgtaggcc 20 2022202534

<210> 458 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 458 gatgagcaag catccattca 20

<210> 459 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 459 aaagacagga gcgtgagcat 20

<210> 460 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 460 ctcaacttcg cttgcccttt 20

<210> 461 <211> 21 <212> DNA <213> Artificial Sequence Page 184

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic primer

<400> 461 tgggaaacag aacgatgaac t 21 2022202534

<210> 462 <211> 2835 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 462 ggtggttacg gtccaggcgc tggtcaacaa ggtccaggaa gtggtggtca acaaggacct 60

ggcggtcaag gaccctacgg tagtggccaa caaggtccag gtggagcagg acagcagggt 120

ccgggaggcc aaggacctta cggaccaggt gctgctgctg ccgccgctgc cgctgccgga 180

ggttacggtc caggagccgg acaacagggt ccaggtggag ctggacaaca aggtccagga 240

tcacaaggtc ctggtggaca aggtccatac ggtcctggtg ctggtcaaca gggaccaggt 300

agtcaaggac ctggttcagg tggtcagcag ggtccaggag gacagggtcc ttacggccct 360

tctgccgctg cagcagcagc cgctgccgca ggaggatacg gacctggtgc tggacaacga 420

tctcaaggac caggaggaca aggtccttat ggacctggcg ctggccaaca aggacctggt 480

tctcagggtc caggttcagg aggccaacaa ggcccaggag gtcaaggacc atacggacca 540

tccgctgcgg cagctgcagc tgctgcaggt ggatatggcc caggagccgg acaacagggt 600

cctggttcac aaggtccagg atctggtggt caacagggac caggcggcca gggaccttat 660

ggtccaggag ccgctgcagc agcagcagct gttggaggtt acggccctgg tgccggtcaa 720

caaggcccag gatctcaggg tcctggatct ggaggacaac aaggtcctgg aggtcagggt 780

ccatacggac cttcagcagc agctgctgct gcagccgctg gtggttatgg acctggtgct 840

ggtcaacaag gaccgggttc tcagggtccg ggttcaggag gtcagcaggg ccctggtgga 900

caaggacctt atggacctag tgcggctgca gcagctgccg ccgcaggtgg ttacggtcca 960

ggcgctggtc aacaaggtcc aggaagtggt ggtcaacaag gacctggcgg tcaaggaccc 1020 Page 185

37324PCT_CRF_sequencelisting 19 Apr 2022

tacggtagtg gccaacaagg tccaggtgga gcaggacagc agggtccggg aggccaagga 1080

ccttacggac caggtgctgc tgctgccgcc gctgccgctg ccggaggtta cggtccagga 1140

gccggacaac agggtccagg tggagctgga caacaaggtc caggatcaca aggtcctggt 1200

ggacaaggtc catacggtcc tggtgctggt caacagggac caggtagtca aggacctggt 1260 2022202534

tcaggtggtc agcagggtcc aggaggacag ggtccttacg gcccttctgc cgctgcagca 1320

gcagccgctg ccgcaggagg atacggacct ggtgctggac aacgatctca aggaccagga 1380

ggacaaggtc cttatggacc tggcgctggc caacaaggac ctggttctca gggtccaggt 1440

tcaggaggcc aacaaggccc aggaggtcaa ggaccatacg gaccatccgc tgcggcagct 1500

gcagctgctg caggtggata tggcccagga gccggacaac agggtcctgg ttcacaaggt 1560

ccaggatctg gtggtcaaca gggaccaggc ggccagggac cttatggtcc aggagccgct 1620

gcagcagcag cagctgttgg aggttacggc cctggtgccg gtcaacaagg cccaggatct 1680

cagggtcctg gatctggagg acaacaaggt cctggaggtc agggtccata cggaccttca 1740

gcagcagctg ctgctgcagc cgctggtggt tatggacctg gtgctggtca acaaggaccg 1800

ggttctcagg gtccgggttc aggaggtcag cagggccctg gtggacaagg accttatgga 1860

cctagtgcgg ctgcagcagc tgccgccgca ggtggttacg gtccaggcgc tggtcaacaa 1920

ggtccaggaa gtggtggtca acaaggacct ggcggtcaag gaccctacgg tagtggccaa 1980

caaggtccag gtggagcagg acagcagggt ccgggaggcc aaggacctta cggaccaggt 2040

gctgctgctg ccgccgctgc cgctgccgga ggttacggtc caggagccgg acaacagggt 2100

ccaggtggag ctggacaaca aggtccagga tcacaaggtc ctggtggaca aggtccatac 2160

ggtcctggtg ctggtcaaca gggaccaggt agtcaaggac ctggttcagg tggtcagcag 2220

ggtccaggag gacagggtcc ttacggccct tctgccgctg cagcagcagc cgctgccgca 2280

ggaggatacg gacctggtgc tggacaacga tctcaaggac caggaggaca aggtccttat 2340

ggacctggcg ctggccaaca aggacctggt tctcagggtc caggttcagg aggccaacaa 2400

ggcccaggag gtcaaggacc atacggacca tccgctgcgg cagctgcagc tgctgcaggt 2460

ggatatggcc caggagccgg acaacagggt cctggttcac aaggtccagg atctggtggt 2520

caacagggac caggcggcca gggaccttat ggtccaggag ccgctgcagc agcagcagct 2580 Page 186

37324PCT_CRF_sequencelisting 19 Apr 2022

gttggaggtt acggccctgg tgccggtcaa caaggcccag gatctcaggg tcctggatct 2640

ggaggacaac aaggtcctgg aggtcagggt ccatacggac cttcagcagc agctgctgct 2700

gcagccgctg gtggttatgg acctggtgct ggtcaacaag gaccgggttc tcagggtccg 2760

ggttcaggag gtcagcaggg ccctggtgga caaggacctt atggacctag tgcggctgca 2820 2022202534

gcagctgccg ccgca 2835

<210> 463 <211> 945 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polypeptide

<400> 463 Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly 1 5 10 15

Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly 20 25 30

Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly 35 40 45

Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro 50 55 60

Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly 65 70 75 80

Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln 85 90 95

Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro 100 105 110

Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala 115 120 125 Page 187

37324PCT_CRF_sequencelisting 19 Apr 2022

Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Arg Ser Gln Gly Pro 130 135 140

Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly 145 150 155 160 2022202534

Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly 165 170 175

Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 180 185 190

Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser 195 200 205

Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala 210 215 220

Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly Gln 225 230 235 240

Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro 245 250 255

Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala 260 265 270

Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln 275 280 285

Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr 290 295 300

Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro 305 310 315 320

Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly 325 330 335 Page 188

37324PCT_CRF_sequencelisting 19 Apr 2022

Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly Pro Gly Gly Ala Gly 340 345 350

Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala 355 360 365 2022202534

Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln 370 375 380

Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly 385 390 395 400

Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser 405 410 415

Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro 420 425 430

Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 435 440 445

Gly Pro Gly Ala Gly Gln Arg Ser Gln Gly Pro Gly Gly Gln Gly Pro 450 455 460

Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly 465 470 475 480

Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser 485 490 495

Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly 500 505 510

Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly 515 520 525

Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala 530 535 540 Page 189

37324PCT_CRF_sequencelisting 19 Apr 2022

Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser 545 550 555 560

Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro 565 570 575 2022202534

Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly 580 585 590

Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly 595 600 605

Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala 610 615 620

Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln 625 630 635 640

Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr 645 650 655

Gly Ser Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly 660 665 670

Gly Gln Gly Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala 675 680 685

Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala 690 695 700

Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr 705 710 715 720

Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser 725 730 735

Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala 740 745 750 Page 190

37324PCT_CRF_sequencelisting 19 Apr 2022

Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly 755 760 765

Gln Arg Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala 770 775 780 2022202534

Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln 785 790 795 800

Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala 805 810 815

Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly 820 825 830

Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly 835 840 845

Pro Tyr Gly Pro Gly Ala Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr 850 855 860

Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser 865 870 875 880

Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala 885 890 895

Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln 900 905 910

Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro 915 920 925

Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala 930 935 940

Ala 945 Page 191

37324PCT_CRF_sequencelisting 19 Apr 2022

<210> 464 <211> 315 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic 2022202534

polypeptide

<400> 464 Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gly Gly 1 5 10 15

Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Ser Gly Gln Gln Gly 20 25 30

Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly 35 40 45

Pro Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro 50 55 60

Gly Ala Gly Gln Gln Gly Pro Gly Gly Ala Gly Gln Gln Gly Pro Gly 65 70 75 80

Ser Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln 85 90 95

Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro 100 105 110

Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala 115 120 125

Ala Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Arg Ser Gln Gly Pro 130 135 140

Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly 145 150 155 160

Page 192

37324PCT_CRF_sequencelisting 19 Apr 2022

Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly 165 170 175

Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 180 185 190

Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser 2022202534

195 200 205

Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr Gly Pro Gly Ala 210 215 220

Ala Ala Ala Ala Ala Ala Val Gly Gly Tyr Gly Pro Gly Ala Gly Gln 225 230 235 240

Gln Gly Pro Gly Ser Gln Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro 245 250 255

Gly Gly Gln Gly Pro Tyr Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala 260 265 270

Ala Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln 275 280 285

Gly Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Gln Gly Pro Tyr 290 295 300

Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 305 310 315

<210> 465 <211> 4324 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 465 ggagttgaat cacatcttac tggatagcga gctttttgac gaagtgaaaa tttctaattt 60

Page 193

37324PCT_CRF_sequencelisting 19 Apr 2022

taaacaagag gaaggggtca aaaacggaga tatcttatac ttggaaaaag agatgacaat 120

cagtgatttc atcaattttg tatctagttg gccttctgtg ttttcgtgga agcagcaacg 180

aggaaaggag ggtatcctag atgattttta caacgaactg aacgactgct ttgagggggg 240

taacatgaaa gtaatatgga actccgtcct agtatttgcc aggaggaagc aaagggttgt 300

ataggcttta gtacttatag aggaaacggg gttacgtgca agcgcgcatg cctgagcttt 360 2022202534

gagggggggg actttcacat ctcttcttct cacacttagc cctaacacag agaataataa 420

aaagcattgc aagatgagtg ttgtcagcaa gcaatacgac atccacgaag gcattatctt 480

tgtaattgaa ttgaccccgg agcttcacgc gccggcttca gaagggaaat ctcagctcca 540

gatcatctta gagaatgtca gtgaggttat ttctgagcta atcattacct tgcccggtac 600

aggaataggg tgttacctta ttaattacga cggtggtcaa aacgacgaaa tttaccccat 660

ttttgagtta caagacctga atttggaaat gatgaaacaa ttgtaccaag tcttggagga 720

ccatgtaagt gggcttaatc ctctcgagaa gcaattccca attgaacaca gtaaaccgtt 780

atcagccact ctgttctttc acttaaggtc tcttttttac atggcgaaga ctcataagcg 840

tactggaaga cattacaact tgaaaaagat tttcttgttc actaataacg ataaacctta 900

caatggaaac tctcagctga gagttccctt gaagaaaacc ctggctgatt acaatgacgt 960

agacattact ttgattccgt ttcttctgaa caagccttca ggtgtcaagt ttgacaagac 1020

ggaatactca gaaattttgt tctatgataa agatgcttgt tcgatgtcaa ttgaggagat 1080

ccgccaacga atttctagac ataaggagat caagcgggtt tacttcacct gtcctttgaa 1140

aatcgcaaat aacttgtgca tttctgtgaa aggttattct atgttttatc atgaaactcc 1200

aaggaagatc aaatttgtcg tcaatgaggg ttcaactttc aaagatgtgg agacaaaatc 1260

tcagtttgtc gatccaacat ccggaaaaga gttttccagt gaacagctga tcaaagcata 1320

tcctctaggt gccgatgctt acattccttt aaactcagag caagtcaaaa caataaatcg 1380

atttaatgat atcatcaata tcccctcttt ggaaattcta ggtttcaggg atatatctaa 1440

ttggttgcca cagtatcagt ttggcaaagc atcgttttta tcccctaata actatggtga 1500

ttttacacat tcgcagagaa catttagttg tcttcagtaa tgtcttgttt cttttgttgc 1560

agtggtgagc cattttgact tcgtgaaagt ttctttagaa tagttgtttc cagaggccaa 1620

Page 194

37324PCT_CRF_sequencelisting 19 Apr 2022

acattccacc cgtagtaaag tgcaagcgta ggaagaccaa gactggcata aatcaggtat 1680

aagtgtcgag cactggcagg tgatcttctg aaagtttcta ctagcagata agatccagta 1740

gtcatgcata tggcaacaat gtaccgtgtg gatctaagaa cgcgtcctac taaccttcgc 1800

attcgttggt ccagtttgtt gttatcgatc aacgtgacaa ggttgtcgat tccgcgtaag 1860

catgcatacc caaggacgcc tgttgcaatt ccaagtgagc cagttccaac aatctttgta 1920 2022202534

atattagagc acttcattgt gttgcgcttg aaagtaaaat gcgaacaaat taagagataa 1980

tctcgaaacc gcgacttcaa acgccaatat gatgtgcggc acacaataag cgttcatatc 2040

cgctgggtga ctttctcgct ttaaaaaatt atccgaaaaa atttttgacg gctagctcag 2100

tcctaggtac gctagcatta aagaggagaa aatggctaaa ctgacctctg ctgttccggt 2160

tctgaccgct cgtgacgttg ctggtgctgt tgagttctgg accgaccgtc tgggtttctc 2220

tcgtgacttc gttgaagacg acttcgctgg tgttgttcgt gacgacgtta ccctgttcat 2280

ctctgctgtt caggaccagg ttgttccgga caacaccctg gcttgggttt gggttcgtgg 2340

tctggacgaa ctgtacgctg aatggtctga agttgtttct accaacttcc gtgacgcttc 2400

tggtccggct atgaccgaaa tcggtgaaca gccgtggggt cgtgagttcg ctctgcgtga 2460

cccggctggt aactgcgttc acttcgttgc tgaagaacag gactaacacg tccgacggcg 2520

gcccacgggt cccaggcctc ggagatccgt cccccttttc ctttgtcgat atcatgtaat 2580

tagttatgtc acgcttacat tcacgccctc cccccacatc cgctctaacc gaaaaggaag 2640

gagttagaca acctgaagtc taggtcccta tttatttttt tatagttatg ttagtattaa 2700

gaacgttatt tatatttcaa atttttcttt tttttctgta cagacgcgtg tacgcatgta 2760

acattatact gaaaaccttg cttgagaagg ttttgggacg ctcgaaggct ttaatttgca 2820

agctgtatta gtttcacttt tcagcaacct ggtcggaaag atccacatca agaatggata 2880

ccaaccccaa gagtatgaaa atccttccct acaatggcac ttcaaaatgt tacgtgacga 2940

ttaccttcaa ttggaacacg atatcgacat cagtgacccc cttgagaaac aaaagtacat 3000

aaacagcctc gatgagacaa aaaccaagat catgaaacta cgggactatg tcaaggaaac 3060

tgccgatgat gacgaccctt cacggcttgc caacactctc aaagagctca accaagagct 3120

gaacaaaatt tccaactttg atatcatcgc caataagaag ccaaagaccc ccacgacagt 3180

Page 195

37324PCT_CRF_sequencelisting 19 Apr 2022

agaccctgtt cctactgatg atgacatcat caacgcctgg aaggcaggaa ctctgaacgg 3240

tttcaaggtg gatcaattac gaaaatacgt aaggtcacga aacaactttc tggagacggc 3300

ctccaaaaag gcagatctca tcgccaacat tgacaagtac tttcagcaga agttcaaaga 3360

gactaaggcc tgattcgtgt tccttacttt ttcctcgcaa cgtgtttttt tcccaccaca 3420

ttgcctatgt tgtaatgcaa tgcagatgct ggcccagttt ttgacgattc tcgaaaattg 3480 2022202534

gcattttcgt cgatgccatt ggccaaactg aaaattcaag acaaaataga ttggatttta 3540

tctgcaacgt cttccaccta cacaaccact ctacaaactt cagacaaaca tgtttataaa 3600

agcagctact agatccaaaa tgacaagttc gttattctct actacgtttg ttgtggcatt 3660

tggattggtg gctagcaaca acctcttgcc atgtcctgtt gaccactcta tgaataacga 3720

gactccgcaa gaattgaaac cattgcaggc tgaatcttct actagaaagt tgaactcttc 3780

cgcttaagtc aaataaaact actgacacag atgatgcaca gaaacaacgg atcacgctct 3840

tgactgatta gtcccgtcat tttggttctc attttcttca cagtcaccta tcaatgtatg 3900

atcacctgga aggatttccc tacgatactt caaatctttt acttgataat attactcatt 3960

atggctcagg aatgcagact gcctgattca agacgctgct cttcttattt aacacttgta 4020

cactaacccc atggaagcca gggaagggaa taaccatctc tctggtaata aatcggtctt 4080

tatttatgca tagaaaagga atctattata tttcgttcat ttggcactct gctaactgta 4140

gattaacggg tctcgtaaat tcaaaatctt cttccgatca aaccggggtg aaatattact 4200

tctcgtgcat agctaatttt caaataaccg tcctaaaatg aacggtcatt tacctggact 4260

ctcttgccaa atgggcaaca aaacataaag ctgatcagaa cgtaactagt ctctcggaat 4320

ccat 4324

<210> 466 <211> 22 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide

<400> 466 ggagttgaat cacatcttac tg 22 Page 196

37324PCT_CRF_sequencelisting 19 Apr 2022

<210> 467 <211> 1099 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic 2022202534

polynucleotide

<400> 467 gacaactaaa tgttctctgc gaatgtgtaa aatcaccata gttattaggg gataaaaacg 60

atgctttgcc aaactgatac tgtggcaacc aattagatat atccctgaaa cctagaattt 120

ccaaagaggg gatattgatg atatcattaa atcgatttat tgttttgact tgctctgagt 180

ttaaaggaat gtaagcatcg gcacctagag gatatgcttt gatcagctgt tcactggaaa 240

actcttttcc ggatgttgga tcgacaaact gagattttgt ctccacatct ttgaaagttg 300

aaccctcatt gacgacaaat ttgatcttcc ttggagtttc atgataaaac atagaataac 360

ctttcacaga aatgcacaag ttatttgcga ttttcaaagg acaggtgaag taaacccgct 420

tgatctcctt atgtctagaa attcgttggc ggatctcctc aattgacatc gaacaagcat 480

ctttatcata gaacaaaatt tctgagtatt ccgtcttgtc aaacttgaca cctgaaggct 540

tgttcagaag aaacggaatc aaagtaatgt ctacgtcatt gtaatcagcc agggttttct 600

tcaagggaac tctcagctga gagtttccat tgtaaggttt atcgttatta gtgaacaaga 660

aaatcttttt caagttgtaa tgtcttccag tacgcttatg agtcttcgcc atgtaaaaaa 720

gagaccttaa gtgaaagaac agagtggctg ataacggttt actgtgttca attgggaatt 780

gcttctcgag aggattaagc ccacttacat ggtcctccaa gacttggtac aattgtttca 840

tcatttccaa attcaggtct tgtaactcaa aaatggggta aatttcgtcg ttttgaccac 900

cgtcgtaatt aataaggtaa caccctattc ctgtaccggg caaggtaatg attagctcag 960

aaataacctc actgacattc tctaagatga tctggagctg agatttccct tctgaagccg 1020

gcgcgtgaag ctccggggtc aattcaatta caaagataat gccttcgtgg atgtcgtatt 1080

gcttgctgac aacactcat 1099

<210> 468 Page 197

37324PCT_CRF_sequencelisting 19 Apr 2022

<211> 549 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 468 2022202534

tcaggcctta gtctctttga acttctgctg aaagtacttg tcaatgttgg cgatgagatc 60

tgcctttttg gaggccgtct ccagaaagtt gtttcgtgac cttacgtatt ttcgtaattg 120

atccaccttg aaaccgttca gagttcctgc cttccaggcg ttgatgatgt catcatcagt 180

aggaacaggg tctactgtcg tgggggtctt tggcttctta ttggcgatga tatcaaagtt 240

ggaaattttg ttcagctctt ggttgagctc tttgagagtg ttggcaagcc gtgaagggtc 300

gtcatcatcg gcagtttcct tgacatagtc ccgtagtttc atgatcttgg tttttgtctc 360

atcgaggctg tttatgtact tttgtttctc aagggggtca ctgatgtcga tatcgtgttc 420

caattgaagg taatcgtcac gtaacatttt gaagtgccat tgtagggaag gattttcata 480

ctcttggggt tggtatccat tcttgatgtg gatctttccg accaggttgc tgaaaagtga 540

aactaatac 549

<210> 469 <211> 552 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 469 ttcagtaatg tcttgtttct tttgttgcag tggtgagcca ttttgacttc gtgaaagttt 60

ctttagaata gttgtttcca gaggccaaac attccacccg tagtaaagtg caagcgtagg 120

aagaccaaga ctggcataaa tcaggtataa gtgtcgagca ctggcaggtg atcttctgaa 180

agtttctact agcagataag atccagtagt catgcatatg gcaacaatgt accgtgtgga 240

tctaagaacg cgtcctacta accttcgcat tcgttggtcc agtttgttgt tatcgatcaa 300

cgtgacaagg ttgtcgattc cgcgtaagca tgcataccca aggacgcctg ttgcaattcc 360

Page 198

37324PCT_CRF_sequencelisting 19 Apr 2022

aagtgagcca gttccaacaa tctttgtaat attagagcac ttcattgtgt tgcgcttgaa 420

agtaaaatgc gaacaaatta agagataatc tcgaaaccgc gacttcaaac gccaatatga 480

tgtgcggcac acaataagcg ttcatatccg ctgggtgact ttctcgcttt aaaaaattat 540

ccgaaaaaat tt 552 2022202534

<210> 470 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide

<400> 470 cagaggccaa acattccacc 20

<210> 471 <211> 14 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide

<400> 471 ttaaagagga gaaa 14

<210> 472 <211> 375 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 472 atggctaaac tgacctctgc tgttccggtt ctgaccgctc gtgacgttgc tggtgctgtt 60

gagttctgga ccgaccgtct gggtttctct cgtgacttcg ttgaagacga cttcgctggt 120

gttgttcgtg acgacgttac cctgttcatc tctgctgttc aggaccaggt tgttccggac 180

aacaccctgg cttgggtttg ggttcgtggt ctggacgaac tgtacgctga atggtctgaa 240 Page 199

37324PCT_CRF_sequencelisting 19 Apr 2022

gttgtttcta ccaacttccg tgacgcttct ggtccggcta tgaccgaaat cggtgaacag 300

ccgtggggtc gtgagttcgc tctgcgtgac ccggctggta actgcgttca cttcgttgct 360

gaagaacagg actaa 375

<210> 473 2022202534

<211> 318 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 473 cacgtccgac ggcggcccac gggtcccagg cctcggagat ccgtccccct tttcctttgt 60

cgatatcatg taattagtta tgtcacgctt acattcacgc cctcccccca catccgctct 120

aaccgaaaag gaaggagtta gacaacctga agtctaggtc cctatttatt tttttatagt 180

tatgttagta ttaagaacgt tatttatatt tcaaattttt cttttttttc tgtacagacg 240

cgtgtacgca tgtaacatta tactgaaaac cttgcttgag aaggttttgg gacgctcgaa 300

ggctttaatt tgcaagct 318

<210> 474 <211> 20 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide

<400> 474 aggagttaga caacctgaag 20

<210> 475 <211> 23 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide Page 200

37324PCT_CRF_sequencelisting 19 Apr 2022

<400> 475 gtaactagtc tctcggaatc cat 23

<210> 476 <211> 1623 <212> DNA <213> Artificial Sequence 2022202534

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 476 cttcagagta cagaagatta agtgagagaa ttctaccgtt cgtatagcat acattatacg 60

aagttatttc agtaatgtct tgtttctttt gttgcagtgg tgagccattt tgacttcgtg 120

aaagtttctt tagaatagtt gtttccagag gccaaacatt ccacccgtag taaagtgcaa 180

gcgtaggaag accaagactg gcataaatca ggtataagtg tcgagcactg gcaggtgatc 240

ttctgaaagt ttctactagc agataagatc cagtagtcat gcatatggca acaatgtacc 300

gtgtggatct aagaacgcgt cctactaacc ttcgcattcg ttggtccagt ttgttgttat 360

cgatcaacgt gacaaggttg tcgattccgc gtaagcatgc atacccaagg acgcctgttg 420

caattccaag tgagccagtt ccaacaatct ttgtaatatt agagcacttc attgtgttgc 480

gcttgaaagt aaaatgcgaa caaattaaga gataatctcg aaaccgcgac ttcaaacgcc 540

aatatgatgt gcggcacaca ataagcgttc atatccgctg ggtgactttc tcgctttaaa 600

aaattatccg aaaaaatttt tgacggctag ctcagtccta ggtacgctag cattaaagag 660

gagaaaatga ctactcttga tgacacagcc tacagatata ggacatcagt tccgggtgac 720

gcagaggcta tcgaagcctt ggacggttca ttcactactg atacggtgtt tagagtcacc 780

gctacaggtg atggcttcac cttgagagag gttcctgtag acccaccctt aacgaaagtt 840

ttccctgatg acgaatcgga tgacgagtct gatgctggtg aggacggtga ccctgattcc 900

agaacatttg tcgcatacgg agatgatggt gacctggctg gctttgttgt ggtgtcctac 960

agcggatgga atcgtagact cacagttgag gacatcgaag ttgcacctga acatcgtggt 1020

cacggtgttg gtcgtgcact gatgggactg gcaacagagt ttgctagaga aagaggagcc 1080

ggacatttgt ggttagaagt gaccaatgtc aacgctcctg ctattcacgc atataggcga 1140 Page 201

37324PCT_CRF_sequencelisting 19 Apr 2022

atgggtttca ctttgtgcgg tcttgatact gctttgtatg acggaactgc ttctgatggt 1200

gaacaagctc tttacatgag tatgccatgt ccatagcacg tccgacggcg gcccacgggt 1260

cccaggcctc ggagatccgt cccccttttc ctttgtcgat atcatgtaat tagttatgtc 1320

acgcttacat tcacgccctc cccccacatc cgctctaacc gaaaaggaag gagttagaca 1380 2022202534

acctgaagtc taggtcccta tttatttttt tatagttatg ttagtattaa gaacgttatt 1440

tatatttcaa atttttcttt tttttctgta cagacgcgtg tacgcatgta acattatact 1500

gaaaaccttg cttgagaagg ttttgggacg ctcgaaggct ttaatttgca agctataact 1560

tcgtatagca tacattatac cttgttatgc ggccgcaaga agttgattga gactttcaac 1620

gag 1623

<210> 477 <211> 27 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide

<400> 477 cttcagagta cagaagatta agtgaga 27

<210> 478 <211> 34 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide

<400> 478 taccgttcgt atagcataca ttatacgaag ttat 34

<210> 479 <211> 552 <212> DNA <213> Artificial Sequence

<220> Page 202

37324PCT_CRF_sequencelisting 19 Apr 2022

<223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 479 ttcagtaatg tcttgtttct tttgttgcag tggtgagcca ttttgacttc gtgaaagttt 60

ctttagaata gttgtttcca gaggccaaac attccacccg tagtaaagtg caagcgtagg 120

aagaccaaga ctggcataaa tcaggtataa gtgtcgagca ctggcaggtg atcttctgaa 180 2022202534

agtttctact agcagataag atccagtagt catgcatatg gcaacaatgt accgtgtgga 240

tctaagaacg cgtcctacta accttcgcat tcgttggtcc agtttgttgt tatcgatcaa 300

cgtgacaagg ttgtcgattc cgcgtaagca tgcataccca aggacgcctg ttgcaattcc 360

aagtgagcca gttccaacaa tctttgtaat attagagcac ttcattgtgt tgcgcttgaa 420

agtaaaatgc gaacaaatta agagataatc tcgaaaccgc gacttcaaac gccaatatga 480

tgtgcggcac acaataagcg ttcatatccg ctgggtgact ttctcgcttt aaaaaattat 540

ccgaaaaaat tt 552

<210> 480 <211> 14 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide

<400> 480 ttaaagagga gaaa 14

<210> 481 <211> 570 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 481 atgactactc ttgatgacac agcctacaga tataggacat cagttccggg tgacgcagag 60

gctatcgaag ccttggacgg ttcattcact actgatacgg tgtttagagt caccgctaca 120

Page 203

37324PCT_CRF_sequencelisting 19 Apr 2022

ggtgatggct tcaccttgag agaggttcct gtagacccac ccttaacgaa agttttccct 180

gatgacgaat cggatgacga gtctgatgct ggtgaggacg gtgaccctga ttccagaaca 240

tttgtcgcat acggagatga tggtgacctg gctggctttg ttgtggtgtc ctacagcgga 300

tggaatcgta gactcacagt tgaggacatc gaagttgcac ctgaacatcg tggtcacggt 360

gttggtcgtg cactgatggg actggcaaca gagtttgcta gagaaagagg agccggacat 420 2022202534

ttgtggttag aagtgaccaa tgtcaacgct cctgctattc acgcatatag gcgaatgggt 480

ttcactttgt gcggtcttga tactgctttg tatgacggaa ctgcttctga tggtgaacaa 540

gctctttaca tgagtatgcc atgtccatag 570

<210> 482 <211> 318 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 482 cacgtccgac ggcggcccac gggtcccagg cctcggagat ccgtccccct tttcctttgt 60

cgatatcatg taattagtta tgtcacgctt acattcacgc cctcccccca catccgctct 120

aaccgaaaag gaaggagtta gacaacctga agtctaggtc cctatttatt tttttatagt 180

tatgttagta ttaagaacgt tatttatatt tcaaattttt cttttttttc tgtacagacg 240

cgtgtacgca tgtaacatta tactgaaaac cttgcttgag aaggttttgg gacgctcgaa 300

ggctttaatt tgcaagct 318

<210> 483 <211> 34 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide

<400> 483 ataacttcgt atagcataca ttataccttg ttat 34

Page 204

37324PCT_CRF_sequencelisting 19 Apr 2022

<210> 484 <211> 35 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic oligonucleotide 2022202534

<400> 484 gcggccgcaa gaagttgatt gagactttca acgag 35

<210> 485 <211> 3869 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 485 tactacaggc tggctgttcc tcgcatggtg tttaatgtcc tgactgggtt ttcgtttatc 60

ggtattaccg gagccacctt gactgtaagg gaacgatact ggactaagag agtaatgcga 120

aaggcaacag cgtttctggc gaacctaatc aatgacggtt acgagtttac tactcctaaa 180

gccagtctta ttttgctaga gcgagtcaac gcttacttaa agggccaggg acctaattat 240

gacatcgatt ttgacgagca ggaggcgttc attaaagaaa tggaggagtt gaggacctct 300

ggtggatatg agaacagata ctcatattca ggaaccgatg aaacacccag agatccgggt 360

tgcctgtttc ttcccattgc tttaaataaa tggcactttg atgtgctaga ctgcctgagg 420

atatacggta ctcaggaaga tctggaatct aaattattaa gtgttcagca attggtgtta 480

caatgttgca tgaagcacag tggcatgact ccagacatgg tctttgcaac ggaagtagct 540

cagaagccga ccttcgaaga cgacatagtt tgtgatgata ttgacgctta tgcccagggg 600

ggtgattgtc tagattattg ttacacgcca agcaattact ccagaacttt agaaattcat 660

ggcaagattg ctaccttaca acgagagctg gggctatgct ataatattct cggaattttg 720

gaccgttttt ccgattaagg tttttagctc cattgcgcca acccccgctc tccagactcc 780

ttcgttatcc agcattcagc atggacaggt tcaaaaaata aaatttcttg atatgggtcc 840

Page 205

37324PCT_CRF_sequencelisting 19 Apr 2022

acttcaaaca tgcgcctacc tgtaggaaaa aaaaagagaa cataaatatg ccgcgaacag 900

aaaacgtaat gtactgttct atatataaac tgttcagatc aatcataaat tctcagtttc 960

aaactttccg ctcagccaga ttttattcgt aaagaacgca tcattggctc tatgttgaag 1020

gatcagttct tgttatgggt tgctttgata gcgagcgtac cggtttccgg cgtgatggca 1080

gctcctagcg agtccgggca taacacggtt gaaaaacgag atgccaaaaa cgttgttggc 1140 2022202534

gttcaacagt tggacttctt cagagtacag aagattaagt gagagaattc taccgttcgt 1200

atagcataca ttatacgaag ttatttcagt aatgtcttgt ttcttttgtt gcagtggtga 1260

gccattttga cttcgtgaaa gtttctttag aatagttgtt tccagaggcc aaacattcca 1320

cccgtagtaa agtgcaagcg taggaagacc aagactggca taaatcaggt ataagtgtcg 1380

agcactggca ggtgatcttc tgaaagtttc tactagcaga taagatccag tagtcatgca 1440

tatggcaaca atgtaccgtg tggatctaag aacgcgtcct actaaccttc gcattcgttg 1500

gtccagtttg ttgttatcga tcaacgtgac aaggttgtcg attccgcgta agcatgcata 1560

cccaaggacg cctgttgcaa ttccaagtga gccagttcca acaatctttg taatattaga 1620

gcacttcatt gtgttgcgct tgaaagtaaa atgcgaacaa attaagagat aatctcgaaa 1680

ccgcgacttc aaacgccaat atgatgtgcg gcacacaata agcgttcata tccgctgggt 1740

gactttctcg ctttaaaaaa ttatccgaaa aaatttttga cggctagctc agtcctaggt 1800

acgctagcat taaagaggag aaaatgacta ctcttgatga cacagcctac agatatagga 1860

catcagttcc gggtgacgca gaggctatcg aagccttgga cggttcattc actactgata 1920

cggtgtttag agtcaccgct acaggtgatg gcttcacctt gagagaggtt cctgtagacc 1980

cacccttaac gaaagttttc cctgatgacg aatcggatga cgagtctgat gctggtgagg 2040

acggtgaccc tgattccaga acatttgtcg catacggaga tgatggtgac ctggctggct 2100

ttgttgtggt gtcctacagc ggatggaatc gtagactcac agttgaggac atcgaagttg 2160

cacctgaaca tcgtggtcac ggtgttggtc gtgcactgat gggactggca acagagtttg 2220

ctagagaaag aggagccgga catttgtggt tagaagtgac caatgtcaac gctcctgcta 2280

ttcacgcata taggcgaatg ggtttcactt tgtgcggtct tgatactgct ttgtatgacg 2340

gaactgcttc tgatggtgaa caagctcttt acatgagtat gccatgtcca tagcacgtcc 2400

Page 206

37324PCT_CRF_sequencelisting 19 Apr 2022

gacggcggcc cacgggtccc aggcctcgga gatccgtccc ccttttcctt tgtcgatatc 2460

atgtaattag ttatgtcacg cttacattca cgccctcccc ccacatccgc tctaaccgaa 2520

aaggaaggag ttagacaacc tgaagtctag gtccctattt atttttttat agttatgtta 2580

gtattaagaa cgttatttat atttcaaatt tttctttttt ttctgtacag acgcgtgtac 2640

gcatgtaaca ttatactgaa aaccttgctt gagaaggttt tgggacgctc gaaggcttta 2700 2022202534

atttgcaagc tataacttcg tatagcatac attatacctt gttatgcggc cgcaagaagt 2760

tgattgagac tttcaacgag ggtccccttc agctaccttt ctctctgttt ggtagttatt 2820

ctcggcgtgt gtatagtata gtataaaagg gcctacattg gataggcttc aacattcctc 2880

aataaacaaa catccaacat cgcgcattcc gcatttcgca tttcacattt cgcgcctgcc 2940

ttcctttagg ttctttgaat catcatcaat cgtcgccgtc tacatcagag caggacttat 3000

ctttgccttc cccaaaaatt gccactccgt caaatagatt cttttgaatc cttgactatt 3060

tttgcctaaa taggtttttg ttagtttttc ttcaaagccc aaaagaaact ctatttagat 3120

tcatccagaa acaatctttt tctcacccca tttcgaagtg ccgtggagca cagacataaa 3180

aagatgacta ccgttcaacc tacagggcca gacaggctca ccctgccgca tattctactg 3240

gaattcaacg atggctcctc gcagcatgca gtgatcgagc taagcatgaa cgaggggatt 3300

aatatatcca cccatgagtg gaatccatcc actaatgagc aatcgccacg ggaagagaga 3360

gcaccacccc aacaatccaa tccatcgcat catccagaat catcgaacat agctactcaa 3420

agtcccgctc aggaaaccga gactcagccc ggcattccag gactagatag gcctgccttt 3480

gatacctcgg caacggggtc gtcagaacag gttgacccag tacagggaag gatcctggat 3540

gatattatag gccaatcatt aaggacttcc gaagaagacg ataccgaatc ccgccagaga 3600

ccacgagacc agaagaacat tatgatcacc gtgaattact tgtacgcaga cgacacaaat 3660

tccagaagtg ctaatacaaa caaccagacg cccaataaca cttctagaac ttccgacagt 3720

gaacgtgtgg gctccttatc gttgcacgtt ccggatctac cagataatgc cgacgattac 3780

tatatcgatg tactcattaa actaaccaca agcattgccc tcagcgtcat cacgtccatg 3840

atcaagaaac gattagggct tagcaggga 3869

<210> 486 Page 207

37324PCT_CRF_sequencelisting 19 Apr 2022

<211> 1157 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 486 2022202534

tactacaggc tggctgttcc tcgcatggtg tttaatgtcc tgactgggtt ttcgtttatc 60

ggtattaccg gagccacctt gactgtaagg gaacgatact ggactaagag agtaatgcga 120

aaggcaacag cgtttctggc gaacctaatc aatgacggtt acgagtttac tactcctaaa 180

gccagtctta ttttgctaga gcgagtcaac gcttacttaa agggccaggg acctaattat 240

gacatcgatt ttgacgagca ggaggcgttc attaaagaaa tggaggagtt gaggacctct 300

ggtggatatg agaacagata ctcatattca ggaaccgatg aaacacccag agatccgggt 360

tgcctgtttc ttcccattgc tttaaataaa tggcactttg atgtgctaga ctgcctgagg 420

atatacggta ctcaggaaga tctggaatct aaattattaa gtgttcagca attggtgtta 480

caatgttgca tgaagcacag tggcatgact ccagacatgg tctttgcaac ggaagtagct 540

cagaagccga ccttcgaaga cgacatagtt tgtgatgata ttgacgctta tgcccagggg 600

ggtgattgtc tagattattg ttacacgcca agcaattact ccagaacttt agaaattcat 660

ggcaagattg ctaccttaca acgagagctg gggctatgct ataatattct cggaattttg 720

gaccgttttt ccgattaagg tttttagctc cattgcgcca acccccgctc tccagactcc 780

ttcgttatcc agcattcagc atggacaggt tcaaaaaata aaatttcttg atatgggtcc 840

acttcaaaca tgcgcctacc tgtaggaaaa aaaaagagaa cataaatatg ccgcgaacag 900

aaaacgtaat gtactgttct atatataaac tgttcagatc aatcataaat tctcagtttc 960

aaactttccg ctcagccaga ttttattcgt aaagaacgca tcattggctc tatgttgaag 1020

gatcagttct tgttatgggt tgctttgata gcgagcgtac cggtttccgg cgtgatggca 1080

gctcctagcg agtccgggca taacacggtt gaaaaacgag atgccaaaaa cgttgttggc 1140

gttcaacagt tggactt 1157

<210> 487 <211> 1089 Page 208

37324PCT_CRF_sequencelisting 19 Apr 2022

<212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 487 ggtccccttc agctaccttt ctctctgttt ggtagttatt ctcggcgtgt gtatagtata 60 2022202534

gtataaaagg gcctacattg gataggcttc aacattcctc aataaacaaa catccaacat 120

cgcgcattcc gcatttcgca tttcacattt cgcgcctgcc ttcctttagg ttctttgaat 180

catcatcaat cgtcgccgtc tacatcagag caggacttat ctttgccttc cccaaaaatt 240

gccactccgt caaatagatt cttttgaatc cttgactatt tttgcctaaa taggtttttg 300

ttagtttttc ttcaaagccc aaaagaaact ctatttagat tcatccagaa acaatctttt 360

tctcacccca tttcgaagtg ccgtggagca cagacataaa aagatgacta ccgttcaacc 420

tacagggcca gacaggctca ccctgccgca tattctactg gaattcaacg atggctcctc 480

gcagcatgca gtgatcgagc taagcatgaa cgaggggatt aatatatcca cccatgagtg 540

gaatccatcc actaatgagc aatcgccacg ggaagagaga gcaccacccc aacaatccaa 600

tccatcgcat catccagaat catcgaacat agctactcaa agtcccgctc aggaaaccga 660

gactcagccc ggcattccag gactagatag gcctgccttt gatacctcgg caacggggtc 720

gtcagaacag gttgacccag tacagggaag gatcctggat gatattatag gccaatcatt 780

aaggacttcc gaagaagacg ataccgaatc ccgccagaga ccacgagacc agaagaacat 840

tatgatcacc gtgaattact tgtacgcaga cgacacaaat tccagaagtg ctaatacaaa 900

caaccagacg cccaataaca cttctagaac ttccgacagt gaacgtgtgg gctccttatc 960

gttgcacgtt ccggatctac cagataatgc cgacgattac tatatcgatg tactcattaa 1020

actaaccaca agcattgccc tcagcgtcat cacgtccatg atcaagaaac gattagggct 1080

tagcaggga 1089

<210> 488 <211> 3964 <212> DNA <213> Artificial Sequence

Page 209

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 488 gccttctcgt gcaatcagag ctgttgaaag agagaagagg gcacacggaa gctgctgttc 60

aattgtgtga attgaccgga ttacaacctg ctggagtgat aggagagctg gttcgtgacg 120 2022202534

aggacggctc tatgatgcga ttagacgact gtgttcagtt tggtctccgc cacaacgtaa 180

aaattatcaa ccttgaccag atcattgaat acatggattc caagaacagc tagatacgat 240

ggataggaat acagagatat catgattgag gaacgtaaga gctttttcga aagtgtgagt 300

ttgtggtgag ggccaggcgg tggggaggtg gtggggagcc tccttggtcg aatgtagata 360

tagtaagcaa gacacaagag cgcgcgaagt cttcaacgag gcggcgttgg gtcttgtacg 420

caacgtaatg actacacagt tgagcttgtc gcgaaccggt cgacattttg atcatgcata 480

ctatgttgag acaccatctc gtactattgc ggcaaccagc tgtaaatttg actaattaaa 540

gctgatgaag gatgcagggc gtcgtcaatt ttttgattga ttgcatttaa ttgtttgagc 600

cattcaaggc tgaatgcccg gcaccctaga cccttcttgt gagtactata aacccgcagg 660

cagggtaccc ttggccttct gcgagactac cagtcataac gtatatccac aatgtactag 720

taatagcccc ggaaaactct aatcccacag aacgtctaac gcctcctatg tcatcgatac 780

ccattcgcac tactgccatg gcccccctta cgtgatcatt tcacttactc ccgcctaagc 840

ttcgcccaca tgcctgcgtt ttgccaagat ttactgacga gtttggttta ctcatcctct 900

atttataact actagacttt caccattctt caccaccctc gtgccaatga tcatcaacca 960

cttggtattg acagccctca gcattgcact agcaagtgcg caactccaat cgcctttcac 1020

ttcagagtac agaagattaa gtgagagaat tctaccgttc gtatagcata cattatacga 1080

agttatttca gtaatgtctt gtttcttttg ttgcagtggt gagccatttt gacttcgtga 1140

aagtttcttt agaatagttg tttccagagg ccaaacattc cacccgtagt aaagtgcaag 1200

cgtaggaaga ccaagactgg cataaatcag gtataagtgt cgagcactgg caggtgatct 1260

tctgaaagtt tctactagca gataagatcc agtagtcatg catatggcaa caatgtaccg 1320

tgtggatcta agaacgcgtc ctactaacct tcgcattcgt tggtccagtt tgttgttatc 1380

gatcaacgtg acaaggttgt cgattccgcg taagcatgca tacccaagga cgcctgttgc 1440 Page 210

37324PCT_CRF_sequencelisting 19 Apr 2022

aattccaagt gagccagttc caacaatctt tgtaatatta gagcacttca ttgtgttgcg 1500

cttgaaagta aaatgcgaac aaattaagag ataatctcga aaccgcgact tcaaacgcca 1560

atatgatgtg cggcacacaa taagcgttca tatccgctgg gtgactttct cgctttaaaa 1620

aattatccga aaaaattttt gacggctagc tcagtcctag gtacgctagc attaaagagg 1680 2022202534

agaaaatgac tactcttgat gacacagcct acagatatag gacatcagtt ccgggtgacg 1740

cagaggctat cgaagccttg gacggttcat tcactactga tacggtgttt agagtcaccg 1800

ctacaggtga tggcttcacc ttgagagagg ttcctgtaga cccaccctta acgaaagttt 1860

tccctgatga cgaatcggat gacgagtctg atgctggtga ggacggtgac cctgattcca 1920

gaacatttgt cgcatacgga gatgatggtg acctggctgg ctttgttgtg gtgtcctaca 1980

gcggatggaa tcgtagactc acagttgagg acatcgaagt tgcacctgaa catcgtggtc 2040

acggtgttgg tcgtgcactg atgggactgg caacagagtt tgctagagaa agaggagccg 2100

gacatttgtg gttagaagtg accaatgtca acgctcctgc tattcacgca tataggcgaa 2160

tgggtttcac tttgtgcggt cttgatactg ctttgtatga cggaactgct tctgatggtg 2220

aacaagctct ttacatgagt atgccatgtc catagcacgt ccgacggcgg cccacgggtc 2280

ccaggcctcg gagatccgtc ccccttttcc tttgtcgata tcatgtaatt agttatgtca 2340

cgcttacatt cacgccctcc ccccacatcc gctctaaccg aaaaggaagg agttagacaa 2400

cctgaagtct aggtccctat ttattttttt atagttatgt tagtattaag aacgttattt 2460

atatttcaaa tttttctttt ttttctgtac agacgcgtgt acgcatgtaa cattatactg 2520

aaaaccttgc ttgagaaggt tttgggacgc tcgaaggctt taatttgcaa gctataactt 2580

cgtatagcat acattatacc ttgttatgcg gccgcaagaa gttgattgag actttcaacg 2640

agctggctct gcttctggta cttcttcagg tgcatcttct gctactcaaa atgacgaaac 2700

atccactgat cttggagctc cagctgcatc tttaagtgca acgccatgtc tttttgccat 2760

cttgctgctc atgttgtagt agactttttt tttcactgag tttttatgta ctactgatta 2820

cattgtgtag gtgtaatgat gtgcactata atactaatat agtcaaaatg ctacagagga 2880

aagtgcaggt tgcctgtggt ggtttttctt attagcaccc tctgaacact ctttacctct 2940

aacatcctca gccatgctaa tcgcgcataa aataaatctt cgaacttttt tccattttat 3000 Page 211

37324PCT_CRF_sequencelisting 19 Apr 2022

gctcataaag cttccttact gtcaccttat caaaagagct tttgccacta aagtagtcac 3060

acccagaatt gctcccgaat atcgtccaac aatgctagga tctgtggaaa gtttgacaaa 3120

taatttgaac accttgagct tgaagcttcc tgaagttaat atccaaggct cctttccaga 3180

aagtaaccca gtggaccttt tgagaaacta catcactcaa gaacttagta aaatttctgg 3240 2022202534

agttgacaaa gaattgattt tcccagcctt ggaatggggt accacactgg aaaaaggtga 3300

tcttttgatc ccagttcctc gtctgagaat aaagggtgct aatcctaaag atttagccga 3360

acaatgggct gctgcattcc caaagggtgg atatcttaaa gacgttattg cgcaaggacc 3420

tttcttgcag ttctttttta acacatcggt tctgtacaag ttggtgatat ctgatgctct 3480

ggagagaggc gatgactttg gtgcacttcc tctaggaaag ggacaaaaag ttatagtgga 3540

gttttcttct ccaaatattg ccaaaccttt ccacgctggc catcttagaa gtacaatcat 3600

cggtggtttt atttccaatc tgtatgaaaa gctgggtcat gaagttatga ggatgaatta 3660

tttgggagac tggggaaaac aatttggtgt tcttgcagta ggatttgagc gttacggtga 3720

tgaggcaaaa ttaaagactg atccaatcaa ccatttgttt gaggtctatg ttaaaatcaa 3780

ccaagatatt aaggctcaat cagagtctac tgaggagatt gcagaagggc aatcattaga 3840

tgaccaggca agagcttttt tcaagaaaat ggaaaatggc gacgaatcgg ctgtaagctt 3900

gtggaaaaga ttccgtgagt tatccattga gaagtacatt gatacttatg cccgcctcaa 3960

catc 3964

<210> 489 <211> 1019 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 489 gccttctcgt gcaatcagag ctgttgaaag agagaagagg gcacacggaa gctgctgttc 60

aattgtgtga attgaccgga ttacaacctg ctggagtgat aggagagctg gttcgtgacg 120

aggacggctc tatgatgcga ttagacgact gtgttcagtt tggtctccgc cacaacgtaa 180

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37324PCT_CRF_sequencelisting 19 Apr 2022

aaattatcaa ccttgaccag atcattgaat acatggattc caagaacagc tagatacgat 240

ggataggaat acagagatat catgattgag gaacgtaaga gctttttcga aagtgtgagt 300

ttgtggtgag ggccaggcgg tggggaggtg gtggggagcc tccttggtcg aatgtagata 360

tagtaagcaa gacacaagag cgcgcgaagt cttcaacgag gcggcgttgg gtcttgtacg 420

caacgtaatg actacacagt tgagcttgtc gcgaaccggt cgacattttg atcatgcata 480 2022202534

ctatgttgag acaccatctc gtactattgc ggcaaccagc tgtaaatttg actaattaaa 540

gctgatgaag gatgcagggc gtcgtcaatt ttttgattga ttgcatttaa ttgtttgagc 600

cattcaaggc tgaatgcccg gcaccctaga cccttcttgt gagtactata aacccgcagg 660

cagggtaccc ttggccttct gcgagactac cagtcataac gtatatccac aatgtactag 720

taatagcccc ggaaaactct aatcccacag aacgtctaac gcctcctatg tcatcgatac 780

ccattcgcac tactgccatg gcccccctta cgtgatcatt tcacttactc ccgcctaagc 840

ttcgcccaca tgcctgcgtt ttgccaagat ttactgacga gtttggttta ctcatcctct 900

atttataact actagacttt caccattctt caccaccctc gtgccaatga tcatcaacca 960

cttggtattg acagccctca gcattgcact agcaagtgcg caactccaat cgcctttca 1019

<210> 490 <211> 1322 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 490 ctggctctgc ttctggtact tcttcaggtg catcttctgc tactcaaaat gacgaaacat 60

ccactgatct tggagctcca gctgcatctt taagtgcaac gccatgtctt tttgccatct 120

tgctgctcat gttgtagtag actttttttt tcactgagtt tttatgtact actgattaca 180

ttgtgtaggt gtaatgatgt gcactataat actaatatag tcaaaatgct acagaggaaa 240

gtgcaggttg cctgtggtgg tttttcttat tagcaccctc tgaacactct ttacctctaa 300

catcctcagc catgctaatc gcgcataaaa taaatcttcg aacttttttc cattttatgc 360

tcataaagct tccttactgt caccttatca aaagagcttt tgccactaaa gtagtcacac 420 Page 213

37324PCT_CRF_sequencelisting 19 Apr 2022

ccagaattgc tcccgaatat cgtccaacaa tgctaggatc tgtggaaagt ttgacaaata 480

atttgaacac cttgagcttg aagcttcctg aagttaatat ccaaggctcc tttccagaaa 540

gtaacccagt ggaccttttg agaaactaca tcactcaaga acttagtaaa atttctggag 600

ttgacaaaga attgattttc ccagccttgg aatggggtac cacactggaa aaaggtgatc 660 2022202534

ttttgatccc agttcctcgt ctgagaataa agggtgctaa tcctaaagat ttagccgaac 720

aatgggctgc tgcattccca aagggtggat atcttaaaga cgttattgcg caaggacctt 780

tcttgcagtt cttttttaac acatcggttc tgtacaagtt ggtgatatct gatgctctgg 840

agagaggcga tgactttggt gcacttcctc taggaaaggg acaaaaagtt atagtggagt 900

tttcttctcc aaatattgcc aaacctttcc acgctggcca tcttagaagt acaatcatcg 960

gtggttttat ttccaatctg tatgaaaagc tgggtcatga agttatgagg atgaattatt 1020

tgggagactg gggaaaacaa tttggtgttc ttgcagtagg atttgagcgt tacggtgatg 1080

aggcaaaatt aaagactgat ccaatcaacc atttgtttga ggtctatgtt aaaatcaacc 1140

aagatattaa ggctcaatca gagtctactg aggagattgc agaagggcaa tcattagatg 1200

accaggcaag agcttttttc aagaaaatgg aaaatggcga cgaatcggct gtaagcttgt 1260

ggaaaagatt ccgtgagtta tccattgaga agtacattga tacttatgcc cgcctcaaca 1320

tc 1322

<210> 491 <211> 3932 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 491 gacgagacgc tgttcctttc aacttgtcca cttggactga caagtcaaca cctgttacta 60

attcttttgt catctctcag tatgaagaca cgcgtgttcc tcaatcagcc accagttcta 120

cacatccaaa catacctaaa cacgccaaag agtatccgtt agcaaatggg ccacctgggt 180

ggtgttggaa ttcccattcc agtatgtcga cagaccaacc aatatatcca ggacaccaat 240

Page 214

37324PCT_CRF_sequencelisting 19 Apr 2022

atccaccacc gcttcagcag cactaccact ttgcttcacc caggcaacta tcaaactcta 300

gctctgggac gtcatccgtt cctttccaac caccccctgc tggtcaatta caaccacaag 360

gtaattctat gttcatacac atgccatttt cgctaaatgg cccaccagct gctggacagc 420

aattgatacc accccaagga ctagcctcaa tacctgtcgg ccccggcaac aacagttccc 480

tattggttag ccaaggtgca cctggcggct attctttagc ttcaccagcg ttgtcaccgg 540 2022202534

tagatgcgac cttcgaagat cccgtcaaga gactgcccaa aaagcggaca aaaactggat 600

gtctcacttg ccgtaagaga cgaatcaaat gtgacgaacg caagccgttc tgtttcaact 660

gtgaaaaaag caaaaaggtg tgtactggtt ttacgcatct attcaaagat ccccctagca 720

aatcctaccc tcccagttca gatggtgcct cccctgttgc caatgaccac cctgtccccc 780

caaggcaaaa ctttggtgaa ttgaggggca gtctgaatta catcatcaac tagaagaatg 840

cttattcctt ttctctactg tataatcacg acgttatgtc ctttaatata agaaacgaca 900

attaaaccac tttaggtgga cataatccat ttctggatgc tgttcgatgt gtagtgtcta 960

aaccgatact gagatttctc tttctctttc tctttttttt ttttttccta ccatttcctt 1020

caagaaaata cacctttcga cagatcatca taaatggtgg cctctcttca cacttcagag 1080

tacagaagat taagtgagag aattctaccg ttcgtatagc atacattata cgaagttatt 1140

tcagtaatgt cttgtttctt ttgttgcagt ggtgagccat tttgacttcg tgaaagtttc 1200

tttagaatag ttgtttccag aggccaaaca ttccacccgt agtaaagtgc aagcgtagga 1260

agaccaagac tggcataaat caggtataag tgtcgagcac tggcaggtga tcttctgaaa 1320

gtttctacta gcagataaga tccagtagtc atgcatatgg caacaatgta ccgtgtggat 1380

ctaagaacgc gtcctactaa ccttcgcatt cgttggtcca gtttgttgtt atcgatcaac 1440

gtgacaaggt tgtcgattcc gcgtaagcat gcatacccaa ggacgcctgt tgcaattcca 1500

agtgagccag ttccaacaat ctttgtaata ttagagcact tcattgtgtt gcgcttgaaa 1560

gtaaaatgcg aacaaattaa gagataatct cgaaaccgcg acttcaaacg ccaatatgat 1620

gtgcggcaca caataagcgt tcatatccgc tgggtgactt tctcgcttta aaaaattatc 1680

cgaaaaaatt tttgacggct agctcagtcc taggtacgct agcattaaag aggagaaaat 1740

gactactctt gatgacacag cctacagata taggacatca gttccgggtg acgcagaggc 1800

Page 215

37324PCT_CRF_sequencelisting 19 Apr 2022

tatcgaagcc ttggacggtt cattcactac tgatacggtg tttagagtca ccgctacagg 1860

tgatggcttc accttgagag aggttcctgt agacccaccc ttaacgaaag ttttccctga 1920

tgacgaatcg gatgacgagt ctgatgctgg tgaggacggt gaccctgatt ccagaacatt 1980

tgtcgcatac ggagatgatg gtgacctggc tggctttgtt gtggtgtcct acagcggatg 2040

gaatcgtaga ctcacagttg aggacatcga agttgcacct gaacatcgtg gtcacggtgt 2100 2022202534

tggtcgtgca ctgatgggac tggcaacaga gtttgctaga gaaagaggag ccggacattt 2160

gtggttagaa gtgaccaatg tcaacgctcc tgctattcac gcatataggc gaatgggttt 2220

cactttgtgc ggtcttgata ctgctttgta tgacggaact gcttctgatg gtgaacaagc 2280

tctttacatg agtatgccat gtccatagca cgtccgacgg cggcccacgg gtcccaggcc 2340

tcggagatcc gtcccccttt tcctttgtcg atatcatgta attagttatg tcacgcttac 2400

attcacgccc tccccccaca tccgctctaa ccgaaaagga aggagttaga caacctgaag 2460

tctaggtccc tatttatttt tttatagtta tgttagtatt aagaacgtta tttatatttc 2520

aaatttttct tttttttctg tacagacgcg tgtacgcatg taacattata ctgaaaacct 2580

tgcttgagaa ggttttggga cgctcgaagg ctttaatttg caagctataa cttcgtatag 2640

catacattat accttgttat gcggccgcaa gaagttgatt gagactttca acgagtgatc 2700

gactacttgg cctccgccgt gaaaactcaa ttagatgtta gctccaaatt aatgaacctg 2760

gtacaagatg ataaatagga actcaaatac aaagcctacc attaatgact gttttatttt 2820

tatactaaag tagctaaagg gtgattatca aggagtggtt aacgatctat tcctagcagg 2880

gcactcagct catcgatctt tccaatatcg gcgtataacg cttccacttc tatcaacgta 2940

tcttcgttaa aaagaccacc tctggtggga actaatcctt ctgctgccgc ctctgctaaa 3000

ctctgtcttc gaatccgttt cttactaaca tcagcttcga cagataagcc actcttcttt 3060

atctttttct tagatcctgt tttgaatctc agggacttta ctggtgccat aacaacttcc 3120

tgttccagta ccttgttctt cttactcttt tttggtatta aagaatgtcc cgccttgagt 3180

cctcgatcat ccttggccat actcaatcgt ctagtagtgc tgttgaaatg ctgtaaagaa 3240

gaggaatatc ttcttaaatg gttggtatct ttttcagcaa ccacaccttt gtttcggaaa 3300

gcggataatg gcacattgct tggattgata gaagaagcta taaaagccca tcctgcgttt 3360

Page 216

37324PCT_CRF_sequencelisting 19 Apr 2022

ggagcagttt gattgctctg agttactatg ttcaactgtg tattggcaaa agccttagag 3420

tcgctgtctg attcgcttat attgagtaaa tcatccaggt ccaatagagg aacagaacca 3480

gtctgcttcc cttttggttt tgtacgatcc ctaattgcac ccttcacaga aagttctacc 3540

cgtttggact ttatactgtc tttgttctct gatactgatc gcattgaaaa cccatcaata 3600

atctcaaagg gtttgccaca gtccgaggtg gtccaaattc caatcactgg agggatagga 3660 2022202534

tccactttgg aagatgccag aacttctttt gcaattttgg taccaatttt tttattggat 3720

gttttgggaa gagcttcatc ttcatcagtg gagttgctgc tttcgttgtc atctactttt 3780

tggtcatctt ctagttcgtc gtcgtctgaa gcaatagcat ctgaggagga cgcatctcct 3840

tcacctttga aaaagtaatt aaataggtag gagtcatcat cagaatcttg ttcttggtct 3900

gatccccttt cgacggcagc ttgaatgttg tt 3932

<210> 492 <211> 1072 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 492 gacgagacgc tgttcctttc aacttgtcca cttggactga caagtcaaca cctgttacta 60

attcttttgt catctctcag tatgaagaca cgcgtgttcc tcaatcagcc accagttcta 120

cacatccaaa catacctaaa cacgccaaag agtatccgtt agcaaatggg ccacctgggt 180

ggtgttggaa ttcccattcc agtatgtcga cagaccaacc aatatatcca ggacaccaat 240

atccaccacc gcttcagcag cactaccact ttgcttcacc caggcaacta tcaaactcta 300

gctctgggac gtcatccgtt cctttccaac caccccctgc tggtcaatta caaccacaag 360

gtaattctat gttcatacac atgccatttt cgctaaatgg cccaccagct gctggacagc 420

aattgatacc accccaagga ctagcctcaa tacctgtcgg ccccggcaac aacagttccc 480

tattggttag ccaaggtgca cctggcggct attctttagc ttcaccagcg ttgtcaccgg 540

tagatgcgac cttcgaagat cccgtcaaga gactgcccaa aaagcggaca aaaactggat 600

gtctcacttg ccgtaagaga cgaatcaaat gtgacgaacg caagccgttc tgtttcaact 660 Page 217

37324PCT_CRF_sequencelisting 19 Apr 2022

gtgaaaaaag caaaaaggtg tgtactggtt ttacgcatct attcaaagat ccccctagca 720

aatcctaccc tcccagttca gatggtgcct cccctgttgc caatgaccac cctgtccccc 780

caaggcaaaa ctttggtgaa ttgaggggca gtctgaatta catcatcaac tagaagaatg 840

cttattcctt ttctctactg tataatcacg acgttatgtc ctttaatata agaaacgaca 900 2022202534

attaaaccac tttaggtgga cataatccat ttctggatgc tgttcgatgt gtagtgtcta 960

aaccgatact gagatttctc tttctctttc tctttttttt ttttttccta ccatttcctt 1020

caagaaaata cacctttcga cagatcatca taaatggtgg cctctcttca ca 1072

<210> 493 <211> 1237 <212> DNA <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polynucleotide

<400> 493 tgatcgacta cttggcctcc gccgtgaaaa ctcaattaga tgttagctcc aaattaatga 60

acctggtaca agatgataaa taggaactca aatacaaagc ctaccattaa tgactgtttt 120

atttttatac taaagtagct aaagggtgat tatcaaggag tggttaacga tctattccta 180

gcagggcact cagctcatcg atctttccaa tatcggcgta taacgcttcc acttctatca 240

acgtatcttc gttaaaaaga ccacctctgg tgggaactaa tccttctgct gccgcctctg 300

ctaaactctg tcttcgaatc cgtttcttac taacatcagc ttcgacagat aagccactct 360

tctttatctt tttcttagat cctgttttga atctcaggga ctttactggt gccataacaa 420

cttcctgttc cagtaccttg ttcttcttac tcttttttgg tattaaagaa tgtcccgcct 480

tgagtcctcg atcatccttg gccatactca atcgtctagt agtgctgttg aaatgctgta 540

aagaagagga atatcttctt aaatggttgg tatctttttc agcaaccaca cctttgtttc 600

ggaaagcgga taatggcaca ttgcttggat tgatagaaga agctataaaa gcccatcctg 660

cgtttggagc agtttgattg ctctgagtta ctatgttcaa ctgtgtattg gcaaaagcct 720

tagagtcgct gtctgattcg cttatattga gtaaatcatc caggtccaat agaggaacag 780

Page 218

37324PCT_CRF_sequencelisting 19 Apr 2022

aaccagtctg cttccctttt ggttttgtac gatccctaat tgcacccttc acagaaagtt 840

ctacccgttt ggactttata ctgtctttgt tctctgatac tgatcgcatt gaaaacccat 900

caataatctc aaagggtttg ccacagtccg aggtggtcca aattccaatc actggaggga 960

taggatccac tttggaagat gccagaactt cttttgcaat tttggtacca atttttttat 1020

tggatgtttt gggaagagct tcatcttcat cagtggagtt gctgctttcg ttgtcatcta 1080 2022202534

ctttttggtc atcttctagt tcgtcgtcgt ctgaagcaat agcatctgag gaggacgcat 1140

ctccttcacc tttgaaaaag taattaaata ggtaggagtc atcatcagaa tcttgttctt 1200

ggtctgatcc cctttcgacg gcagcttgaa tgttgtt 1237

<210> 494 <211> 5 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic peptide

<400> 494 Ser Gly Ala Gly Gly 1 5

<210> 495 <211> 5 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic peptide

<400> 495 Gly Ser Gly Ala Gly 1 5

<210> 496 <211> 5 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic Page 219

37324PCT_CRF_sequencelisting 19 Apr 2022

peptide

<400> 496 Gly Gly Ser Gly Ala 1 5

<210> 497 <211> 181 2022202534

<212> PRT <213> Aliatypus gulosus

<400> 497 Gly Ala Ala Ser Ser Ser Ser Thr Ile Ile Thr Thr Lys Ser Ala Ser 1 5 10 15

Ala Ser Ala Ala Ala Asp Ala Ser Ala Ala Ala Thr Ala Ser Ala Ala 20 25 30

Ser Arg Ser Ser Ala Asn Ala Ala Ala Ser Ala Phe Ala Gln Ser Phe 35 40 45

Ser Ser Ile Leu Leu Glu Ser Gly Tyr Phe Cys Ser Ile Phe Gly Ser 50 55 60

Ser Ile Ser Ser Ser Tyr Ala Ala Ala Ile Ala Ser Ala Ala Ser Arg 65 70 75 80

Ala Ala Ala Glu Ser Asn Gly Tyr Thr Thr His Ala Tyr Ala Cys Ala 85 90 95

Lys Ala Val Ala Ser Ala Val Glu Arg Val Thr Ser Gly Ala Asp Ala 100 105 110

Tyr Ala Tyr Ala Gln Ala Ile Ser Asp Ala Leu Ser His Ala Leu Leu 115 120 125

Tyr Thr Gly Arg Leu Asn Thr Ala Asn Ala Asn Ser Leu Ala Ser Ala 130 135 140

Phe Ala Tyr Ala Phe Ala Asn Ala Ala Ala Gln Ala Ser Ala Ser Ser 145 150 155 160

Page 220

37324PCT_CRF_sequencelisting 19 Apr 2022

Ala Ser Ala Gly Ala Ala Ser Ala Ser Gly Ala Ala Ser Ala Ser Gly 165 170 175

Ala Gly Ser Ala Ser 180 2022202534

<210> 498 <211> 126 <212> PRT <213> Plectreurys tristis

<400> 498 Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala Gly Ala 1 5 10 15

Gly Ser Gly Ala Ser Thr Ser Val Ser Thr Ser Ser Ser Ser Gly Ser 20 25 30

Gly Ala Gly Ala Gly Ala Gly Ser Gly Ala Gly Ser Gly Ala Gly Ala 35 40 45

Gly Ser Gly Ala Gly Ala Gly Ala Gly Ala Gly Gly Ala Gly Ala Gly 50 55 60

Phe Gly Ser Gly Leu Gly Leu Gly Tyr Gly Val Gly Leu Ser Ser Ala 65 70 75 80

Gln Ala Gln Ala Gln Ala Gln Ala Ala Ala Gln Ala Gln Ala Gln Ala 85 90 95

Gln Ala Gln Ala Tyr Ala Ala Ala Gln Ala Gln Ala Gln Ala Gln Ala 100 105 110

Gln Ala Gln Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 115 120 125

<210> 499 <211> 239 <212> PRT <213> Plectreurys tristis

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<400> 499 Gly Ala Ala Gln Lys Gln Pro Ser Gly Glu Ser Ser Val Ala Thr Ala 1 5 10 15

Ser Ala Ala Ala Thr Ser Val Thr Ser Gly Gly Ala Pro Val Gly Lys 20 25 30 2022202534

Pro Gly Val Pro Ala Pro Ile Phe Tyr Pro Gln Gly Pro Leu Gln Gln 35 40 45

Gly Pro Ala Pro Gly Pro Ser Asn Val Gln Pro Gly Thr Ser Gln Gln 50 55 60

Gly Pro Ile Gly Gly Val Gly Gly Ser Asn Ala Phe Ser Ser Ser Phe 65 70 75 80

Ala Ser Ala Leu Ser Leu Asn Arg Gly Phe Thr Glu Val Ile Ser Ser 85 90 95

Ala Ser Ala Thr Ala Val Ala Ser Ala Phe Gln Lys Gly Leu Ala Pro 100 105 110

Tyr Gly Thr Ala Phe Ala Leu Ser Ala Ala Ser Ala Ala Ala Asp Ala 115 120 125

Tyr Asn Ser Ile Gly Ser Gly Ala Asn Ala Phe Ala Tyr Ala Gln Ala 130 135 140

Phe Ala Arg Val Leu Tyr Pro Leu Val Gln Gln Tyr Gly Leu Ser Ser 145 150 155 160

Ser Ala Lys Ala Ser Ala Phe Ala Ser Ala Ile Ala Ser Ser Phe Ser 165 170 175

Ser Gly Thr Ser Gly Gln Gly Pro Ser Ile Gly Gln Gln Gln Pro Pro 180 185 190

Val Thr Ile Ser Ala Ala Ser Ala Ser Ala Gly Ala Ser Ala Ala Ala 195 200 205

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Val Gly Gly Gly Gln Val Gly Gln Gly Pro Tyr Gly Gly Gln Gln Gln 210 215 220

Ser Thr Ala Ala Ser Ala Ser Ala Ala Ala Ala Thr Ala Thr Ser 225 230 235 2022202534

<210> 500 <211> 182 <212> PRT <213> Araneus gemmoides

<400> 500 Gly Asn Val Gly Tyr Gln Leu Gly Leu Lys Val Ala Asn Ser Leu Gly 1 5 10 15

Leu Gly Asn Ala Gln Ala Leu Ala Ser Ser Leu Ser Gln Ala Val Ser 20 25 30

Ala Val Gly Val Gly Ala Ser Ser Asn Ala Tyr Ala Asn Ala Val Ser 35 40 45

Asn Ala Val Gly Gln Val Leu Ala Gly Gln Gly Ile Leu Asn Ala Ala 50 55 60

Asn Ala Gly Ser Leu Ala Ser Ser Phe Ala Ser Ala Leu Ser Ser Ser 65 70 75 80

Ala Ala Ser Val Ala Ser Gln Ser Ala Ser Gln Ser Gln Ala Ala Ser 85 90 95

Gln Ser Gln Ala Ala Ala Ser Ala Phe Arg Gln Ala Ala Ser Gln Ser 100 105 110

Ala Ser Gln Ser Asp Ser Arg Ala Gly Ser Gln Ser Ser Thr Lys Thr 115 120 125

Thr Ser Thr Ser Thr Ser Gly Ser Gln Ala Asp Ser Arg Ser Ala Ser 130 135 140

Ser Ser Ala Ser Gln Ala Ser Ala Ser Ala Phe Ala Gln Gln Ser Ser Page 223

37324PCT_CRF_sequencelisting 19 Apr 2022

145 150 155 160

Ala Ser Leu Ser Ser Ser Ser Ser Phe Ser Ser Ala Phe Ser Ser Ala 165 170 175

Thr Ser Ile Ser Ala Val 180 2022202534

<210> 501 <211> 180 <212> PRT <213> Argiope aurantia

<400> 501 Gly Ser Leu Ala Ser Ser Phe Ala Ser Ala Leu Ser Ala Ser Ala Ala 1 5 10 15

Ser Val Ala Ser Ser Ala Ala Ala Gln Ala Ala Ser Gln Ser Gln Ala 20 25 30

Ala Ala Ser Ala Phe Ser Arg Ala Ala Ser Gln Ser Ala Ser Gln Ser 35 40 45

Ala Ala Arg Ser Gly Ala Gln Ser Ile Ser Thr Thr Thr Thr Thr Ser 50 55 60

Thr Ala Gly Ser Gln Ala Ala Ser Gln Ser Ala Ser Ser Ala Ala Ser 65 70 75 80

Gln Ala Ser Ala Ser Ser Phe Ala Arg Ala Ser Ser Ala Ser Leu Ala 85 90 95

Ala Ser Ser Ser Phe Ser Ser Ala Phe Ser Ser Ala Asn Ser Leu Ser 100 105 110

Ala Leu Gly Asn Val Gly Tyr Gln Leu Gly Phe Asn Val Ala Asn Asn 115 120 125

Leu Gly Ile Gly Asn Ala Ala Gly Leu Gly Asn Ala Leu Ser Gln Ala 130 135 140

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Val Ser Ser Val Gly Val Gly Ala Ser Ser Ser Thr Tyr Ala Asn Ala 145 150 155 160

Val Ser Asn Ala Val Gly Gln Phe Leu Ala Gly Gln Gly Ile Leu Asn 165 170 175 2022202534

Ala Ala Asn Ala 180

<210> 502 <211> 199 <212> PRT <213> Deinopis spinosa

<400> 502 Gly Ala Ser Ala Ser Ala Tyr Ala Ser Ala Ile Ser Asn Ala Val Gly 1 5 10 15

Pro Tyr Leu Tyr Gly Leu Gly Leu Phe Asn Gln Ala Asn Ala Ala Ser 20 25 30

Phe Ala Ser Ser Phe Ala Ser Ala Val Ser Ser Ala Val Ala Ser Ala 35 40 45

Ser Ala Ser Ala Ala Ser Ser Ala Tyr Ala Gln Ser Ala Ala Ala Gln 50 55 60

Ala Gln Ala Ala Ser Ser Ala Phe Ser Gln Ala Ala Ala Gln Ser Ala 65 70 75 80

Ala Ala Ala Ser Ala Gly Ala Ser Ala Gly Ala Gly Ala Ser Ala Gly 85 90 95

Ala Gly Ala Val Ala Gly Ala Gly Ala Val Ala Gly Ala Gly Ala Val 100 105 110

Ala Gly Ala Ser Ala Ala Ala Ala Ser Gln Ala Ala Ala Ser Ser Ser 115 120 125

Ala Ser Ala Val Ala Ser Ala Phe Ala Gln Ser Ala Ser Tyr Ala Leu Page 225

37324PCT_CRF_sequencelisting 19 Apr 2022

130 135 140

Ala Ser Ser Ser Ala Phe Ala Asn Ala Phe Ala Ser Ala Thr Ser Ala 145 150 155 160

Gly Tyr Leu Gly Ser Leu Ala Tyr Gln Leu Gly Leu Thr Thr Ala Tyr 165 170 175 2022202534

Asn Leu Gly Leu Ser Asn Ala Gln Ala Phe Ala Ser Thr Leu Ser Gln 180 185 190

Ala Val Thr Gly Val Gly Leu 195

<210> 503 <211> 171 <212> PRT <213> Nephila clavipes

<400> 503 Gly Ala Thr Ala Ala Ser Tyr Gly Asn Ala Leu Ser Thr Ala Ala Ala 1 5 10 15

Gln Phe Phe Ala Thr Ala Gly Leu Leu Asn Ala Gly Asn Ala Ser Ala 20 25 30

Leu Ala Ser Ser Phe Ala Arg Ala Phe Ser Ala Ser Ala Glu Ser Gln 35 40 45

Ser Phe Ala Gln Ser Gln Ala Phe Gln Gln Ala Ser Ala Phe Gln Gln 50 55 60

Ala Ala Ser Arg Ser Ala Ser Gln Ser Ala Ala Glu Ala Gly Ser Thr 65 70 75 80

Ser Ser Ser Thr Thr Thr Thr Thr Ser Ala Ala Arg Ser Gln Ala Ala 85 90 95

Ser Gln Ser Ala Ser Ser Ser Tyr Ser Ser Ala Phe Ala Gln Ala Ala 100 105 110

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Ser Ser Ser Leu Ala Thr Ser Ser Ala Leu Ser Arg Ala Phe Ser Ser 115 120 125

Val Ser Ser Ala Ser Ala Ala Ser Ser Leu Ala Tyr Ser Ile Gly Leu 130 135 140 2022202534

Ser Ala Ala Arg Ser Leu Gly Ile Ala Asp Ala Ala Gly Leu Ala Gly 145 150 155 160

Val Leu Ala Arg Ala Ala Gly Ala Leu Gly Gln 165 170

<210> 504 <211> 268 <212> PRT <213> Argiope trifasciata

<400> 504 Gly Gly Ala Pro Gly Gly Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala 1 5 10 15

Gly Phe Gly Pro Gly Gly Gly Ala Gly Phe Gly Pro Gly Gly Gly Ala 20 25 30

Gly Phe Gly Pro Gly Gly Ala Ala Gly Gly Pro Gly Gly Pro Gly Gly 35 40 45

Pro Gly Gly Pro Gly Gly Ala Gly Gly Tyr Gly Pro Gly Gly Ala Gly 50 55 60

Gly Tyr Gly Pro Gly Gly Val Gly Pro Gly Gly Ala Gly Gly Tyr Gly 65 70 75 80

Pro Gly Gly Ala Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro Gly Gly 85 90 95

Ala Gly Pro Gly Gly Ala Gly Gly Glu Gly Pro Val Thr Val Asp Val 100 105 110

Asp Val Thr Val Gly Pro Glu Gly Val Gly Gly Gly Pro Gly Gly Ala Page 227

37324PCT_CRF_sequencelisting 19 Apr 2022

115 120 125

Gly Pro Gly Gly Ala Gly Phe Gly Pro Gly Gly Gly Ala Gly Phe Gly 130 135 140

Pro Gly Gly Ala Pro Gly Ala Pro Gly Gly Pro Gly Gly Pro Gly Gly 145 150 155 160 2022202534

Pro Gly Gly Pro Gly Gly Pro Gly Gly Val Gly Pro Gly Gly Ala Gly 165 170 175

Gly Tyr Gly Pro Gly Gly Ala Gly Gly Val Gly Pro Ala Gly Thr Gly 180 185 190

Gly Phe Gly Pro Gly Gly Ala Gly Gly Phe Gly Pro Gly Gly Ala Gly 195 200 205

Gly Phe Gly Pro Gly Gly Ala Gly Gly Phe Gly Pro Ala Gly Ala Gly 210 215 220

Gly Tyr Gly Pro Gly Gly Val Gly Pro Gly Gly Ala Gly Gly Phe Gly 225 230 235 240

Pro Gly Gly Val Gly Pro Gly Gly Ser Gly Pro Gly Gly Ala Gly Gly 245 250 255

Glu Gly Pro Val Thr Val Asp Val Asp Val Ser Val 260 265

<210> 505 <211> 420 <212> PRT <213> Nephila clavipes

<400> 505 Gly Val Ser Tyr Gly Pro Gly Gly Ala Gly Gly Pro Tyr Gly Pro Gly 1 5 10 15

Gly Pro Tyr Gly Pro Gly Gly Glu Gly Pro Gly Gly Ala Gly Gly Pro 20 25 30

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Tyr Gly Pro Gly Gly Val Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr 35 40 45

Gly Pro Gly Gly Ala Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly 50 55 60 2022202534

Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro 65 70 75 80

Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro Gly 85 90 95

Gly Tyr Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro Gly Gly 100 105 110

Ser Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gly Thr 115 120 125

Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly 130 135 140

Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly Gly Ser Gly Pro 145 150 155 160

Gly Gly Phe Gly Pro Gly Gly Ser Gly Pro Gly Gly Tyr Gly Pro Gly 165 170 175

Gly Ser Gly Pro Gly Gly Ala Gly Pro Gly Gly Val Gly Pro Gly Gly 180 185 190

Phe Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala Ala Pro Gly Gly Ala 195 200 205

Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala Gly 210 215 220

Pro Gly Gly Ala Gly Pro Gly Gly Ala Gly Pro Gly Gly Ala Gly Gly 225 230 235 240

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Ala Gly Gly Ala Gly Gly Ser Gly Gly Ala Gly Gly Ser Gly Gly Thr 245 250 255

Thr Ile Ile Glu Asp Leu Asp Ile Thr Ile Asp Gly Ala Asp Gly Pro 260 265 270 2022202534

Ile Thr Ile Ser Glu Glu Leu Pro Ile Ser Gly Ala Gly Gly Ser Gly 275 280 285

Pro Gly Gly Ala Gly Pro Gly Gly Val Gly Pro Gly Gly Ser Gly Pro 290 295 300

Gly Gly Val Gly Pro Gly Gly Ser Gly Pro Gly Gly Val Gly Pro Gly 305 310 315 320

Gly Ser Gly Pro Gly Gly Val Gly Pro Gly Gly Ala Gly Gly Pro Tyr 325 330 335

Gly Pro Gly Gly Ser Gly Pro Gly Gly Ala Gly Gly Ala Gly Gly Pro 340 345 350

Gly Gly Ala Tyr Gly Pro Gly Gly Ser Tyr Gly Pro Gly Gly Ser Gly 355 360 365

Gly Pro Gly Gly Ala Gly Gly Pro Tyr Gly Pro Gly Gly Glu Gly Pro 370 375 380

Gly Gly Ala Gly Gly Pro Tyr Gly Pro Gly Gly Ala Gly Gly Pro Tyr 385 390 395 400

Gly Pro Gly Gly Ala Gly Gly Pro Tyr Gly Pro Gly Gly Glu Gly Gly 405 410 415

Pro Tyr Gly Pro 420

<210> 506 <211> 376 <212> PRT Page 230

37324PCT_CRF_sequencelisting 19 Apr 2022

<213> Latrodectus hesperus

<400> 506 Gly Ile Asn Val Asp Ser Asp Ile Gly Ser Val Thr Ser Leu Ile Leu 1 5 10 15

Ser Gly Ser Thr Leu Gln Met Thr Ile Pro Ala Gly Gly Asp Asp Leu 20 25 30 2022202534

Ser Gly Gly Tyr Pro Gly Gly Phe Pro Ala Gly Ala Gln Pro Ser Gly 35 40 45

Gly Ala Pro Val Asp Phe Gly Gly Pro Ser Ala Gly Gly Asp Val Ala 50 55 60

Ala Lys Leu Ala Arg Ser Leu Ala Ser Thr Leu Ala Ser Ser Gly Val 65 70 75 80

Phe Arg Ala Ala Phe Asn Ser Arg Val Ser Thr Pro Val Ala Val Gln 85 90 95

Leu Thr Asp Ala Leu Val Gln Lys Ile Ala Ser Asn Leu Gly Leu Asp 100 105 110

Tyr Ala Thr Ala Ser Lys Leu Arg Lys Ala Ser Gln Ala Val Ser Lys 115 120 125

Val Arg Met Gly Ser Asp Thr Asn Ala Tyr Ala Leu Ala Ile Ser Ser 130 135 140

Ala Leu Ala Glu Val Leu Ser Ser Ser Gly Lys Val Ala Asp Ala Asn 145 150 155 160

Ile Asn Gln Ile Ala Pro Gln Leu Ala Ser Gly Ile Val Leu Gly Val 165 170 175

Ser Thr Thr Ala Pro Gln Phe Gly Val Asp Leu Ser Ser Ile Asn Val 180 185 190

Asn Leu Asp Ile Ser Asn Val Ala Arg Asn Met Gln Ala Ser Ile Gln Page 231

37324PCT_CRF_sequencelisting 19 Apr 2022

195 200 205

Gly Gly Pro Ala Pro Ile Thr Ala Glu Gly Pro Asp Phe Gly Ala Gly 210 215 220

Tyr Pro Gly Gly Ala Pro Thr Asp Leu Ser Gly Leu Asp Met Gly Ala 225 230 235 240 2022202534

Pro Ser Asp Gly Ser Arg Gly Gly Asp Ala Thr Ala Lys Leu Leu Gln 245 250 255

Ala Leu Val Pro Ala Leu Leu Lys Ser Asp Val Phe Arg Ala Ile Tyr 260 265 270

Lys Arg Gly Thr Arg Lys Gln Val Val Gln Tyr Val Thr Asn Ser Ala 275 280 285

Leu Gln Gln Ala Ala Ser Ser Leu Gly Leu Asp Ala Ser Thr Ile Ser 290 295 300

Gln Leu Gln Thr Lys Ala Thr Gln Ala Leu Ser Ser Val Ser Ala Asp 305 310 315 320

Ser Asp Ser Thr Ala Tyr Ala Lys Ala Phe Gly Leu Ala Ile Ala Gln 325 330 335

Val Leu Gly Thr Ser Gly Gln Val Asn Asp Ala Asn Val Asn Gln Ile 340 345 350

Gly Ala Lys Leu Ala Thr Gly Ile Leu Arg Gly Ser Ser Ala Val Ala 355 360 365

Pro Arg Leu Gly Ile Asp Leu Ser 370 375

<210> 507 <211> 200 <212> PRT <213> Argiope trifasciata

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<400> 507 Gly Ala Gly Tyr Thr Gly Pro Ser Gly Pro Ser Thr Gly Pro Ser Gly 1 5 10 15

Tyr Pro Gly Pro Leu Gly Gly Gly Ala Pro Phe Gly Gln Ser Gly Phe 20 25 30 2022202534

Gly Gly Ser Ala Gly Pro Gln Gly Gly Phe Gly Ala Thr Gly Gly Ala 35 40 45

Ser Ala Gly Leu Ile Ser Arg Val Ala Asn Ala Leu Ala Asn Thr Ser 50 55 60

Thr Leu Arg Thr Val Leu Arg Thr Gly Val Ser Gln Gln Ile Ala Ser 65 70 75 80

Ser Val Val Gln Arg Ala Ala Gln Ser Leu Ala Ser Thr Leu Gly Val 85 90 95

Asp Gly Asn Asn Leu Ala Arg Phe Ala Val Gln Ala Val Ser Arg Leu 100 105 110

Pro Ala Gly Ser Asp Thr Ser Ala Tyr Ala Gln Ala Phe Ser Ser Ala 115 120 125

Leu Phe Asn Ala Gly Val Leu Asn Ala Ser Asn Ile Asp Thr Leu Gly 130 135 140

Ser Arg Val Leu Ser Ala Leu Leu Asn Gly Val Ser Ser Ala Ala Gln 145 150 155 160

Gly Leu Gly Ile Asn Val Asp Ser Gly Ser Val Gln Ser Asp Ile Ser 165 170 175

Ser Ser Ser Ser Phe Leu Ser Thr Ser Ser Ser Ser Ala Ser Tyr Ser 180 185 190

Gln Ala Ser Ala Ser Ser Thr Ser 195 200

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<210> 508 <211> 357 <212> PRT <213> Uloborus diversus

<400> 508 Gly Ala Ser Ala Ala Asp Ile Ala Thr Ala Ile Ala Ala Ser Val Ala 1 5 10 15 2022202534

Thr Ser Leu Gln Ser Asn Gly Val Leu Thr Ala Ser Asn Val Ser Gln 20 25 30

Leu Ser Asn Gln Leu Ala Ser Tyr Val Ser Ser Gly Leu Ser Ser Thr 35 40 45

Ala Ser Ser Leu Gly Ile Gln Leu Gly Ala Ser Leu Gly Ala Gly Phe 50 55 60

Gly Ala Ser Ala Gly Leu Ser Ala Ser Thr Asp Ile Ser Ser Ser Val 65 70 75 80

Glu Ala Thr Ser Ala Ser Thr Leu Ser Ser Ser Ala Ser Ser Thr Ser 85 90 95

Val Val Ser Ser Ile Asn Ala Gln Leu Val Pro Ala Leu Ala Gln Thr 100 105 110

Ala Val Leu Asn Ala Ala Phe Ser Asn Ile Asn Thr Gln Asn Ala Ile 115 120 125

Arg Ile Ala Glu Leu Leu Thr Gln Gln Val Gly Arg Gln Tyr Gly Leu 130 135 140

Ser Gly Ser Asp Val Ala Thr Ala Ser Ser Gln Ile Arg Ser Ala Leu 145 150 155 160

Tyr Ser Val Gln Gln Gly Ser Ala Ser Ser Ala Tyr Val Ser Ala Ile 165 170 175

Val Gly Pro Leu Ile Thr Ala Leu Ser Ser Arg Gly Val Val Asn Ala Page 234

37324PCT_CRF_sequencelisting 19 Apr 2022

180 185 190

Ser Asn Ser Ser Gln Ile Ala Ser Ser Leu Ala Thr Ala Ile Leu Gln 195 200 205

Phe Thr Ala Asn Val Ala Pro Gln Phe Gly Ile Ser Ile Pro Thr Ser 210 215 220 2022202534

Ala Val Gln Ser Asp Leu Ser Thr Ile Ser Gln Ser Leu Thr Ala Ile 225 230 235 240

Ser Ser Gln Thr Ser Ser Ser Val Asp Ser Ser Thr Ser Ala Phe Gly 245 250 255

Gly Ile Ser Gly Pro Ser Gly Pro Ser Pro Tyr Gly Pro Gln Pro Ser 260 265 270

Gly Pro Thr Phe Gly Pro Gly Pro Ser Leu Ser Gly Leu Thr Gly Phe 275 280 285

Thr Ala Thr Phe Ala Ser Ser Phe Lys Ser Thr Leu Ala Ser Ser Thr 290 295 300

Gln Phe Gln Leu Ile Ala Gln Ser Asn Leu Asp Val Gln Thr Arg Ser 305 310 315 320

Ser Leu Ile Ser Lys Val Leu Ile Asn Ala Leu Ser Ser Leu Gly Ile 325 330 335

Ser Ala Ser Val Ala Ser Ser Ile Ala Ala Ser Ser Ser Gln Ser Leu 340 345 350

Leu Ser Val Ser Ala 355

<210> 509 <211> 32 <212> PRT <213> Euprosthenops australis

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<400> 509 Gly Gly Gln Gly Gly Gln Gly Gln Gly Arg Tyr Gly Gln Gly Ala Gly 1 5 10 15

Ser Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 20 25 30 2022202534

<210> 510 <211> 42 <212> PRT <213> Tetragnatha kauaiensis

<400> 510 Gly Gly Leu Gly Gly Gly Gln Gly Ala Gly Gln Gly Gly Gln Gln Gly 1 5 10 15

Ala Gly Gln Gly Gly Tyr Gly Ser Gly Leu Gly Gly Ala Gly Gln Gly 20 25 30

Ala Ser Ala Ala Ala Ala Ala Ala Ala Ala 35 40

<210> 511 <211> 42 <212> PRT <213> Argiope aurantia

<400> 511 Gly Gly Tyr Gly Pro Gly Ala Gly Gln Gln Gly Pro Gly Ser Gln Gly 1 5 10 15

Pro Gly Ser Gly Gly Gln Gln Gly Pro Gly Gly Leu Gly Pro Tyr Gly 20 25 30

Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 35 40

<210> 512 <211> 46 <212> PRT <213> Deinopis spinosa

<400> 512 Gly Pro Gly Gly Tyr Gly Gly Pro Gly Gln Gln Gly Pro Gly Gln Gly Page 236

37324PCT_CRF_sequencelisting 19 Apr 2022

1 5 10 15

Gln Tyr Gly Pro Gly Thr Gly Gln Gln Gly Gln Gly Pro Ser Gly Gln 20 25 30

Gln Gly Pro Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala 35 40 45 2022202534

<210> 513 <211> 42 <212> PRT <213> Nephila clavata

<400> 513 Gly Pro Gly Gly Tyr Gly Leu Gly Gln Gln Gly Pro Gly Gln Gln Gly 1 5 10 15

Pro Gly Gln Gln Gly Pro Ala Gly Tyr Gly Pro Ser Gly Leu Ser Gly 20 25 30

Pro Gly Gly Ala Ala Ala Ala Ala Ala Ala 35 40

<210> 514 <211> 1800 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polypeptide

<220> <221> MISC_FEATURE <222> (7)..(11) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (15)..(19) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> Page 237

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<221> MISC_FEATURE <222> (23)..(27) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (31)..(35) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," 2022202534

"AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (39)..(43) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (47)..(51) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (55)..(59) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (63)..(67) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (4)..(67) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (71)..(90) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (97)..(101) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent Page 238

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <221> MISC_FEATURE <222> (105)..(109) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE 2022202534

<222> (113)..(117) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (121)..(125) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (129)..(133) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (137)..(141) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (145)..(149) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (153)..(157) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (94)..(157) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE Page 239

37324PCT_CRF_sequencelisting 19 Apr 2022

<222> (161)..(180) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (187)..(191) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent 2022202534

<220> <221> MISC_FEATURE <222> (195)..(199) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (203)..(207) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (211)..(215) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (219)..(223) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (227)..(231) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (235)..(239) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (243)..(247) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> Page 240

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<221> MISC_FEATURE <222> (184)..(247) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (251)..(270) 2022202534

<223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (277)..(281) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (285)..(289) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (293)..(297) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (301)..(305) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (309)..(313) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (317)..(321) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (325)..(329) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent Page 241

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <221> MISC_FEATURE <222> (333)..(337) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE 2022202534

<222> (274)..(337) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (341)..(360) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (367)..(371) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (375)..(379) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (383)..(387) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (391)..(395) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (399)..(403) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (407)..(411) Page 242

37324PCT_CRF_sequencelisting 19 Apr 2022

<223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (415)..(419) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent 2022202534

<220> <221> MISC_FEATURE <222> (423)..(427) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (364)..(427) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (431)..(450) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (457)..(461) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (465)..(469) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (473)..(477) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (481)..(485) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> Page 243

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<221> MISC_FEATURE <222> (489)..(493) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (497)..(501) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," 2022202534

"AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (505)..(509) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (513)..(517) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (454)..(517) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (521)..(540) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (547)..(551) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (555)..(559) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (563)..(567) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent Page 244

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <221> MISC_FEATURE <222> (571)..(575) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE 2022202534

<222> (579)..(583) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (587)..(591) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (595)..(599) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (603)..(607) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (544)..(607) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (611)..(630) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (637)..(641) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (645)..(649) Page 245

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<220> <221> MISC_FEATURE <222> (653)..(657) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent 2022202534

<220> <221> MISC_FEATURE <222> (661)..(665) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (669)..(673) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (677)..(681) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (685)..(689) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (693)..(697) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (634)..(697) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (701)..(720) <223> This region may encompass 6‐20 residues

<220> Page 246

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<221> MISC_FEATURE <222> (727)..(731) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (735)..(739) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," 2022202534

"AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (743)..(747) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (751)..(755) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (759)..(763) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (767)..(771) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (775)..(779) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (783)..(787) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (724)..(787) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," Page 247

37324PCT_CRF_sequencelisting 19 Apr 2022

"GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (791)..(810) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE 2022202534

<222> (817)..(821) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (825)..(829) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (833)..(837) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (841)..(845) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (849)..(853) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (857)..(861) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (865)..(869) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (873)..(877) Page 248

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <221> MISC_FEATURE <222> (814)..(877) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent 2022202534

<220> <221> MISC_FEATURE <222> (881)..(900) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (907)..(911) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (915)..(919) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (923)..(927) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (931)..(935) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (939)..(943) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (947)..(951) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> Page 249

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<221> MISC_FEATURE <222> (955)..(959) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (963)..(967) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," 2022202534

"AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (904)..(967) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (971)..(990) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (997)..(1001) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1005)..(1009) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1013)..(1017) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1021)..(1025) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1029)..(1033) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent Page 250

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <221> MISC_FEATURE <222> (1037)..(1041) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE 2022202534

<222> (1045)..(1049) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1053)..(1057) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (994)..(1057) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (1061)..(1080) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (1087)..(1091) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1095)..(1099) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1103)..(1107) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1111)..(1115) Page 251

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <221> MISC_FEATURE <222> (1119)..(1123) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent 2022202534

<220> <221> MISC_FEATURE <222> (1127)..(1131) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1135)..(1139) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1143)..(1147) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1084)..(1147) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (1151)..(1170) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (1177)..(1181) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1185)..(1189) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> Page 252

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<221> MISC_FEATURE <222> (1193)..(1197) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1201)..(1205) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," 2022202534

"AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1209)..(1213) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1217)..(1221) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1225)..(1229) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1233)..(1237) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1174)..(1237) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (1241)..(1260) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (1267)..(1271) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent Page 253

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <221> MISC_FEATURE <222> (1275)..(1279) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE 2022202534

<222> (1283)..(1287) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1291)..(1295) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1299)..(1303) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1307)..(1311) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1315)..(1319) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1323)..(1327) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1264)..(1327) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE Page 254

37324PCT_CRF_sequencelisting 19 Apr 2022

<222> (1331)..(1350) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (1357)..(1361) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent 2022202534

<220> <221> MISC_FEATURE <222> (1365)..(1369) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1373)..(1377) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1381)..(1385) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1389)..(1393) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1397)..(1401) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1405)..(1409) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1413)..(1417) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> Page 255

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<221> MISC_FEATURE <222> (1354)..(1417) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (1421)..(1440) 2022202534

<223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (1447)..(1451) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1455)..(1459) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1463)..(1467) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1471)..(1475) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1479)..(1483) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1487)..(1491) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1495)..(1499) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent Page 256

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <221> MISC_FEATURE <222> (1503)..(1507) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE 2022202534

<222> (1444)..(1507) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (1511)..(1530) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (1537)..(1541) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1545)..(1549) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1553)..(1557) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1561)..(1565) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1569)..(1573) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1577)..(1581) Page 257

37324PCT_CRF_sequencelisting 19 Apr 2022

<220> <221> MISC_FEATURE <222> (1585)..(1589) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent 2022202534

<220> <221> MISC_FEATURE <222> (1593)..(1597) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1534)..(1597) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (1601)..(1620) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (1627)..(1631) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1635)..(1639) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1643)..(1647) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1651)..(1655) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> Page 258

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<221> MISC_FEATURE <222> (1659)..(1663) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1667)..(1671) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," 2022202534

"AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1675)..(1679) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1683)..(1687) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1624)..(1687) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (1691)..(1710) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (1717)..(1721) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1725)..(1729) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1733)..(1737) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent Page 259

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<220> <221> MISC_FEATURE <222> (1741)..(1745) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE 2022202534

<222> (1749)..(1753) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1757)..(1761) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1765)..(1769) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1773)..(1777) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (1714)..(1777) <223> This region may encompass 4‐8 repeating "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent

<220> <221> MISC_FEATURE <222> (1781)..(1800) <223> This region may encompass 6‐20 residues

<220> <221> MISC_FEATURE <222> (1)..(1800) <223> This sequence may encompass 2‐20 "GGY‐[GPG‐X1]n1‐GPS‐(A)n2" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," n1 is 4‐8 and n2 is 6‐20 and some positions may be absent

<400> 514 Page 260

37324PCT_CRF_sequencelisting 19 Apr 2022

Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1 5 10 15

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 20 25 30

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 2022202534

35 40 45

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 50 55 60

Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 65 70 75 80

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly 85 90 95

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 100 105 110

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 115 120 125

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 130 135 140

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser 145 150 155 160

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 165 170 175

Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 180 185 190

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 195 200 205

Page 261

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Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 210 215 220

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 225 230 235 240

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala 2022202534

245 250 255

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly 260 265 270

Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 275 280 285

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 290 295 300

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 305 310 315 320

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 325 330 335

Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 340 345 350

Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa 355 360 365

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 370 375 380

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 385 390 395 400

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 405 410 415

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37324PCT_CRF_sequencelisting 19 Apr 2022

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala 420 425 430

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 435 440 445

Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 2022202534

450 455 460

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 465 470 475 480

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 485 490 495

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 500 505 510

Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 515 520 525

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly 530 535 540

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 545 550 555 560

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 565 570 575

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 580 585 590

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 595 600 605

Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 610 615 620

Page 263

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Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa 625 630 635 640

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 645 650 655

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 2022202534

660 665 670

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 675 680 685

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala 690 695 700

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 705 710 715 720

Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 725 730 735

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 740 745 750

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 755 760 765

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 770 775 780

Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 785 790 795 800

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly 805 810 815

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 820 825 830

Page 264

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Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 835 840 845

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly 850 855 860

Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser 2022202534

865 870 875 880

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 885 890 895

Ala Ala Ala Ala Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 900 905 910

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 915 920 925

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 930 935 940

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly 945 950 955 960

Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala 965 970 975

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly 980 985 990

Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 995 1000 1005

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa 1010 1015 1020

Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1025 1030 1035

Page 265

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Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa 1040 1045 1050

Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 1055 1060 1065

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 2022202534

1070 1075 1080

Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 1085 1090 1095

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa 1100 1105 1110

Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1115 1120 1125

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa 1130 1135 1140

Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 1145 1150 1155

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 1160 1165 1170

Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 1175 1180 1185

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa 1190 1195 1200

Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1205 1210 1215

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa 1220 1225 1230

Page 266

37324PCT_CRF_sequencelisting 19 Apr 2022

Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 1235 1240 1245

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 1250 1255 1260

Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 2022202534

1265 1270 1275

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa 1280 1285 1290

Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1295 1300 1305

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa 1310 1315 1320

Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 1325 1330 1335

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 1340 1345 1350

Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 1355 1360 1365

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa 1370 1375 1380

Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1385 1390 1395

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa 1400 1405 1410

Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 1415 1420 1425

Page 267

37324PCT_CRF_sequencelisting 19 Apr 2022

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 1430 1435 1440

Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 1445 1450 1455

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa 2022202534

1460 1465 1470

Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1475 1480 1485

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa 1490 1495 1500

Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 1505 1510 1515

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 1520 1525 1530

Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 1535 1540 1545

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa 1550 1555 1560

Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1565 1570 1575

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa 1580 1585 1590

Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 1595 1600 1605

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 1610 1615 1620

Page 268

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Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 1625 1630 1635

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa 1640 1645 1650

Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 2022202534

1655 1660 1665

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa 1670 1675 1680

Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 1685 1690 1695

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Gly Gly Tyr 1700 1705 1710

Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa 1715 1720 1725

Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa 1730 1735 1740

Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1745 1750 1755

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa 1760 1765 1770

Xaa Xaa Xaa Xaa Gly Pro Ser Ala Ala Ala Ala Ala Ala Ala Ala 1775 1780 1785

Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1790 1795 1800

<210> 515 <211> 5 <212> PRT <213> Artificial Sequence Page 269

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<220> <223> Description of Artificial Sequence: Synthetic peptide

<400> 515 Ser Gly Gly Gln Gln 1 5 2022202534

<210> 516 <211> 5 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic peptide

<400> 516 Gly Ala Gly Gln Gln 1 5

<210> 517 <211> 5 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic peptide

<400> 517 Gly Gln Gly Pro Tyr 1 5

<210> 518 <211> 4 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic peptide

<400> 518 Ala Gly Gln Gln 1

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<210> 519 <211> 10 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic peptide 2022202534

<220> <221> MISC_FEATURE <222> (1)..(10) <223> This sequence may encompass 2‐10 residues

<400> 519 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1 5 10

<210> 520 <211> 8 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic peptide

<220> <221> MISC_FEATURE <222> (1)..(8) <223> This sequence may encompass 6‐8 residues

<400> 520 His His His His His His His His 1 5

<210> 521 <211> 70 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic polypeptide

<220> <221> MISC_FEATURE Page 271

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<222> (7)..(11) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (15)..(19) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent 2022202534

<220> <221> MISC_FEATURE <222> (23)..(27) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (31)..(35) <223> This region may encompass "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," wherein some positions may be absent

<220> <221> MISC_FEATURE <222> (4)..(67) <223> This region may encompass 4‐8 "GPG‐X1" repeating units, wherein X1 is "SGGQQ," "GAGQQ," "GQGPY," "AGQQ" or "SQ," and some positions may be absent Page 272

37324PCT_CRF_sequencelisting 19 Apr 2022

<400> 521 Gly Gly Tyr Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 1 5 10 15

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 20 25 30 2022202534

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 35 40 45

Xaa Xaa Xaa Gly Pro Gly Xaa Xaa Xaa Xaa Xaa Gly Pro Gly Xaa Xaa 50 55 60

Xaa Xaa Xaa Gly Pro Ser 65 70

<210> 522 <211> 20 <212> PRT <213> Artificial Sequence

<220> <223> Description of Artificial Sequence: Synthetic peptide

<220> <221> MISC_FEATURE <222> (1)..(20) <223> This sequence may encompass 6‐20 residues

<400> 522 Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala 1 5 10 15

Ala Ala Ala Ala 20

Page 273

Claims

1. A Pichiapastorismicroorganism, in which the activity of aYPS1-1 protease and aYPS1-2 protease has been attenuated or eliminated, wherein said microorganism expresses a recombinant polypeptide.

2. The microorganism of claim 1, wherein said YPS1-1 protease comprises a polypeptide sequence at least 95% identical to SEQ ID NO: 67.

3. The microorganism of claim 1, wherein said YPS1-1 protease comprises SEQ ID NO: 67.

4. The microorganism of claim 1 or claim 2, wherein said YPS1-1 protease is encoded by a YPS]-] gene.

5. The microorganism of claim 4, wherein said YPS]-] gene comprises apolynucleotide sequence at least 95% identical to SEQ ID NO: 1.

6. The microorganism of claim 4, wherein said YPS-] gene comprises at least 15, 20, 25, 30, , or 50 contiguous nucleotides of SEQ ID NO: 1.

7. The microorganism of claim 4, wherein said YPS-] gene comprises SEQ ID NO: 1.

8. The microorganism of claim 4, wherein said YPS]-] gene is at locus PASchr4_0584 of said microorganism.

9. The microorganism of any of the above claims, wherein said YPS1-2 protease comprises a polypeptide sequence at least 95% identical to SEQ ID NO: 68.

10. The microorganism of claim 9, wherein said YPS1-2 protease comprises SEQ ID NO: 68.

11. The microorganism of any of the above claims, wherein said YPS1-2 protease is encoded by a YPS1-2 gene.

12. The microorganism of claim 11, wherein said YPS1-2 gene comprises a polynucleotide sequence at least 95% identical to SEQ ID NO: 2.

13. The microorganism of claim 11, wherein said YPS1-2 gene comprises at least 15, 20, 25, 30, , or 50 contiguous nucleotides of SEQ ID NO: 2.

14. The microorganism of claim 11, wherein said YPS1-2 gene comprises SEQ ID NO: 2.

15. The microorganism of claim 11, wherein said YPS1-2 gene is at locus PASchr3_1157 of said microorganism.

16. The microorganism of any of the above claims, wherein, said YPS]-1 gene or said YPS1-2 gene, or both, has been mutated or knocked out.

17. The microorganism of any of the above claims, wherein said microorganism expresses a recombinant protein.

18. The microorganism of claim 17, wherein said recombinant protein comprises at least one block polypeptide sequence from a silk protein.

19. The microorganism of claim 17, wherein said recombinant protein comprises a silk-like polypeptide.

20. The microorganism of claim 19, wherein said silk-like polypeptide comprises one or more repeat sequences {GGY-[GPG-Xi]ni-GPS-(A)n2}n3, wherein

X1= SGGQQorGAGQQorGQGPYorAGQQorSQ;

nI is from 4 to 8;

n2 is from 6 to 20; and

n3 is from 2 to 20.

21. The microorganism of claim 19, wherein said silk-like polypeptide comprises comprises a polypeptide sequence encoded by SEQ ID NO: 462.

22. The microorganism of any of the above claims, wherein the activity of one or more additional proteases has been attenuated or eliminated.

23. The microorganism of claim 22, wherein said one or more additional proteases comprises YPS1-5, MCK7, or YPS1-3.

24. The microorganism of claim 23, wherein said YPS1-5 gene is at locus PASchr3_0688 of said microorganism.

25. The microorganism of claim 23, wherein said MCK7 protease is encoded by aMCK7 gene comprising a polynucleotide sequence at least 95% identical to SEQ ID NO: 7.

26. The microorganism of claim 23, wherein said MCK7 gene comprises at least 15, 20, 25, 30, , or 50 contiguous nucleotides of SEQ ID NO: 7.

27. The microorganism of claim 23, wherein said MCK7 gene comprises SEQ ID NO: 7.

28. The microorganism of claim 23, wherein saidMCK7 gene is at locus PASchrl-1_0379 of said microorganism.

29. The microorganism of claim 23, wherein said YPS1-3 protease is encoded by a YPS1-3 gene comprising a polynucleotide sequence at least 95% identical to SEQ ID NO: 3.

30. The microorganism of claim 23, wherein said YPS1-3 gene comprises at least 15, 20, 25, 30, , or 50 contiguous nucleotides of SEQ ID NO: 3.

31. The microorganism of claim 23, wherein said YPS1-3 gene comprises SEQ ID NO: 3.

32. The microorganism of claim 23, wherein said YPS1-3 gene is at locus PASchr3_0299 of said microorganism.

33. The microorganism of claim 22, wherein said one or more additional proteases comprise a polypeptide sequence at least 95% identical to a polypeptide sequence selected from the group consisting of: SEQ ID NO: 68 - 130.

34. The microorganism of claim 22, wherein said one or more additional proteases comprise a polypeptide sequence selected from the group consisting of: SEQ ID NO: 68 - 130.

35. The microorganism of claim 22, wherein said one or more additional proteases are encoded by a polynucleotide sequence at least 95% identical to a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 3 - 66.

36. The microorganism of claim 22, wherein said one or more additional proteases are encoded by a polynucleotide sequence comprising at least 15, 20, 25, 30, 40, or 50 contiguous nucleotides of a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 3 - 66.

37. The microorganism of any one of claims 22-36, wherein said microorganism comprises a 3X, 4X or 5X protease knockout.

38. A Pichiapastorisengineered microorganism comprising YPS1-1 and YPS1-2 activity reduced by a mutation or deletion of the YPS]-1 gene comprising SEQ ID NO: 1 and the YPS1-2 gene comprising SEQ ID NO: 2, wherein said microorganism further comprises a recombinantly expressed protein comprising a polypeptide sequence encoded by SEQ ID NO: 462.

39. A cell culture comprising a microorganism of any one of claims 1-38.

40. A cell culture comprising a microorganism of any one of claims 17-38, wherein said recombinantly expressed protein is less degraded than a cell culture comprising an otherwise identical Pichapastorismicroorganism whose YPS1-1 and YPS1-2 activity has not been attenuated or eliminated.

41. A method of producing a recombinant protein with a reduced degradation, comprising:

culturing the microorganism of any one of claims 17-37 in a culture medium under conditions suitable for expression of the recombinantly expressed protein; and

isolating the recombinant protein from the microorganism or the culture medium.

42. The method of claim 41, wherein said recombinant protein is secreted from said microorganism, and wherein isolating said recombinant protein comprises collecting a culture medium comprising said secreted recombinant protein.

43. The method of claim 41, wherein said recombinant protein has a decreased level of degradation as compared to said recombinant protein produced by an otherwise identical microorganism wherein said YPS1-1 and said YPS1-2 protease activity has not been attenuated or eliminated.

44. A method of modifying Pichiapastoristo reduce the degradation of a recombinantly expressed protein, comprising knocking out or mutating a gene encoding a YPS1-1 protein and a YPS1-2 protein.

45. The method of claim 44, further comprising knocking out or mutating one or more additional genes encoding a YPS1-3 protein, a YPS1-5 protein, or an MCK7 protein.

46. The method of claim 44, further comprising knocking out one or more genes encoding a protein comprising a polypeptide selected from the group consisting of SEQ ID NO: 68-130.

47. The method of claim 44, wherein said recombinantly expressed protein comprises a polyA sequence comprising at least at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 contiguous alanine residues.

48. The method of claim 44, wherein said recombinantly expressed protein comprises a silk-like polypeptide.

49. The method of claim 48, wherein said silk-like polypeptide comprises one or more repeat sequences {GGY-[GPG-Xi]ni-GPS-(A)n2}n3, wherein

Xi = SGGQQ or GAGQQ or GQGPY or AGQQ or SQ;

nI is from 4 to 8;

n2 is from 6 to 20; and

n3 is from 2 to 20.

50. The method of claim 44, wherein said recombinantly expressed protein comprises a polypeptide sequence encoded by SEQ ID NO: 462.