Fibroblast activation protein alpha binder proteins

Abstract

The technology relates to polypeptides comprising a scaffold comprising a sequence having at least 90% identity to the amino acid sequence of human Stefin A, wherein the scaffold sequence includes (a) an insertion of an amino acid between amino acid positions corresponding to M1 and I2 of the amino acid sequence of human Stefin A and (b) a mutation at an amino acid position corresponding to N32 of the amino acid sequence of human Stefin A, and a heterologous peptide. The technology also relates to human Stefin A variants that bind to fibroblast activation protein alpha and / or human serum albumin.

Description

[0001] FIBROBLAST ACTIVATION PROTEIN ALPHA BINDER PROTEINS

[0002] RELATED APPLICATION

[0003] [1] This application claims the benefit under 35 U.S.C. § 119(e) of U.S. provisional application number 63 / 663,273, filed June 24, 2024, U.S. provisional application number 63 / 663,299, filed June 24, 2024, U.S. provisional application number 63 / 663,393, filed June 24, 2024, U.S. provisional application number 63 / 663,428, filed June 24, 2024, U.S. provisional application number 63 / 703,502, filed October 4, 2024, U.S. provisional application number 63 / 703,579, filed October 4, 2024, U.S. provisional application number 63 / 703,615, filed October 4, 2024, U.S. provisional application number 63 / 711,230, filed October 24, 2024, U.S. provisional application number 63 / 711,380, filed October 24, 2024, U.S. provisional application number 63 / 793,955, filed April 24, 2024, each of which is incorporated by reference herein in its entirety.

[0004] REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0005] [2] The content of the electronic sequence listing (A122470038WO00-SEQ-HJD.xml; Size: 815,448 bytes; and Date of Creation: June 23, 2025) is herein incorporated by reference in its entirety.

[0006] BACKGROUND

[0007] [3] AFFIMER® proteins are small, engineered proteins based on human Stefin A that bind to specific target molecules with high affinity and specificity. They are part of a class of binding proteins known as alternative scaffolds or non-antibody binding proteins. AFFIMER® proteins offer several advantages over other binder proteins, such as antibodies, including size and stability, ease of production, versatility, customizability, and lack of post-translational modification.

[0008] [4] AFFIMER® proteins are smaller and often more stable than antibodies, making them easier to produce and manipulate in various experimental conditions. AFFIMER® proteins can be produced in large quantities using bacterial expression systems, for example, which is often more cost-effective and scalable than antibody production. AFFIMER® proteins can be engineered to bind a wide range of targets, including proteins, small molecules, and even cells. Their binding characteristics can be finetuned through protein engineering, allowing for the development of highly specific reagents for research, diagnostic, and therapeutic applications. Lastly, unlike antibodies, AFFIMER® proteins do not require post-translational modifications, simplifying their production.

[0009] SUMMARY

[0010] [5] Provided herein, in some aspects, are polypeptide scaffolds, for example, AFFIMER® polypeptide scaffolds, based on variants of human Stefin A, which include modification(s) that prevent amino terminal acetylation / oxidation and increase thermal stability, relative to the naturally occurring human Stefin A protein. Thus, the polypeptide scaffolds provided herein are designed to exhibit improved stability, binding affinity, and manufacturability, relative to other polypeptide scaffolds based on variants of human Stefin A.

[0011] [6] Some aspects relate to a polypeptide including: a scaffold including a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1, wherein the scaffold sequence includes (a) an insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 and (b) a mutation at an amino acid position corresponding to N32 of the amino acid sequence of SEQ ID NO: 1; and a heterologous peptide.

[0012] [7] In some embodiments, an insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 is a glycine (G). In some embodiments, a mutation at an amino acid position corresponding to N32 of the amino acid sequence of SEQ ID NO: 1 is N32G.

[0013] [8] In some embodiments, a sequence of the scaffold has at least 95% identity to the amino acid sequence of SEQ ID NO: 2. In some embodiments, a sequence of the scaffold has about 98% identity to the amino acid sequence of SEQ ID NO: 2. In some embodiments, a scaffold includes the amino acid sequence of SEQ ID NO: 2. In some embodiments, a scaffold consists of the amino acid sequence of SEQ ID NO: 2.

[0014] [9] In some embodiments, a heterologous peptide includes an amino acid sequence having a length of about 4 to about 20 amino acids. In some embodiments, a heterologous peptide includes an amino acid sequence having a length of about 8 to about 16 amino acids.

[0015]

[0010] In some embodiments, a heterologous peptide is located in the sequence of the scaffold between amino acid positions corresponding to positions V47 and T51 of the amino acid sequence of SEQ ID NO: 1. In some embodiments, a polypeptide further includes at least one additional heterologous peptide located in the sequence of the scaffold between amino acid positions corresponding to positions L73 and E78 of the amino acid sequence of SEQ ID NO: 1.

[0016]

[0011] In some embodiments, at least one additional heterologous peptide includes an amino acid sequence having a length of about 4 to about 20 amino acids. In some embodiments, at least one additional heterologous peptide includes an amino acid sequence having a length of about 8 to about 16 amino acids.

[0017]

[0012] In some embodiments, a scaffold further comprises a cysteine. In some embodiments, a cysteine is at or near (e.g., within 10 amino acids of) the C-terminus of the scaffold. In some embodiments, a cysteine is at or near (e.g., within 10 amino acids of) the N-terminus of the scaffold. In some embodiments, a cysteine is within Loop 3 of the scaffold (i.e., the region between two heterologous peptides (i.e., between Loop 2 and Loop 4) of the scaffold. In some embodiments, a scaffold further comprises multiple cysteines (e.g., 2, 3, 4 or more cysteines) such that multiple agents, for example, can be conjugated to the scaffold via a cysteine.

[0018]

[0013] Provided herein, in other aspects, are polypeptides that bind specifically to fibroblast activation protein (FAP) alpha.

[0014] Some aspects relate to a polypeptide comprising: a scaffold and a peptide comprising an amino acid sequence selected from the amino acid sequence of any of SEQ ID NOs: 5-108 or SEQ ID NOs: 109-212 (Table 1).

[0019]

[0015] Other aspects relate to a polypeptide comprising: a scaffold; a first peptide comprising an amino acid sequence selected from the amino acid sequence of any of SEQ ID NOs: 5-108; and a second peptide comprising an amino acid sequence selected from the amino acid sequence of any of SEQ ID NOs: 109-212 (Table 1).

[0020]

[0016] In some embodiments, a scaffold comprises a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1.

[0021]

[0017] Yet other aspects relate to a polypeptide comprising: a scaffold comprising a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1; and at least one heterologous peptide, wherein the polypeptide binds specifically to fibroblast activation protein alpha (FAPa) with a Kd of 1x10-6 M or less.

[0022]

[0018] In some embodiments, a scaffold polypeptide comprises two heterologous peptides, each capable of binding specifically to FAPa.

[0023]

[0019] In some embodiments, a scaffold sequence includes an insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1.

[0024]

[0020] In some embodiments, an insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 is a glycine (G).

[0025]

[0021] In some embodiments, a scaffold sequence includes a mutation at an amino acid position corresponding to N32 of the amino acid sequence of SEQ ID NO: 1. In some embodiments, a mutation at an amino acid position corresponding to N32 of the amino acid sequence of SEQ ID NO: 1 is N32G.

[0026]

[0022] In some embodiments, a sequence of the scaffold has at least 95% identity to the amino acid sequence of SEQ ID NO: 2. In some embodiments, a sequence of the scaffold has about 98% identity to the amino acid sequence of SEQ ID NO: 2. In some embodiments, a scaffold comprises the amino acid sequence of SEQ ID NO: 2.

[0027]

[0023] In some embodiments, a scaffold further comprises a cysteine. In some embodiments, a cysteine is at or near (e.g., within 10 amino acids of) the C-terminus of the scaffold. In some embodiments, a cysteine is at or near (e.g., within 10 amino acids of) the N-terminus of the scaffold. In some embodiments, a cysteine is within Loop 3 of the scaffold (i.e., the region between two heterologous peptides (i.e., between Loop 2 and Loop 4) of the scaffold. In some embodiments, a scaffold further comprises multiple cysteines (e.g., 2, 3, 4 or more cysteines) such that multiple agent, for example, can be conjugated to the scaffold via a cysteine.

[0028]

[0024] In some embodiments, a peptide is located in the sequence of the scaffold between amino acid positions corresponding to positions V47 and T51 of the amino acid sequence of SEQ ID NO: 1 or between amino acid positions corresponding to positions L73 and E78 of the amino acid sequence of SEQ ID NO: 1.

[0025] In some embodiments, a first peptide is located in the sequence of the scaffold between amino acid positions corresponding to positions V47 and T51 of the amino acid sequence of SEQ ID NO: 1 and the second peptide is located in the sequence of the scaffold between amino acid positions corresponding to positions L73 and E78 of the amino acid sequence of SEQ ID NO: 1.

[0029]

[0026] In some embodiments, a first peptide comprises the amino acid sequence of SEQ ID NO: 5 and the second peptide comprises the amino acid sequence of SEQ ID NO: 109; or a first peptide comprises the amino acid sequence of SEQ ID NO: 6 and the second peptide comprises the amino acid sequence of SEQ ID NO: 110; or a first peptide comprises the amino acid sequence of SEQ ID NO: 7 and a second peptide comprises the amino acid sequence of SEQ ID NO: 111.

[0030]

[0027] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of any of SEQ ID NOs: 213-316 (Table 2). In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of SEQ ID NO: 213 (FAP-1). In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of SEQ ID NO: 214 (FAP-2). In some embodiments, a polypeptide comprises an amino acid sequence of any of SEQ ID NOs: 213-316 (Table 2). In some embodiments, a polypeptide comprises the amino acid sequence of SEQ ID NO: 213 (FAP-1). In some embodiments, a polypeptide comprises the amino acid sequence of SEQ ID NO: 214 (FAP-2).

[0031]

[0028] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of any of SEQ ID NOs: 317-334 (Table 3). In some embodiments, a polypeptide comprises an amino acid sequence of any of SEQ ID NOs: 317-334 (Table 3).

[0032]

[0029] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of any of SEQ ID NOs: 335-352 (Table 4). In some embodiments, a polypeptide comprises an amino acid sequence of any of SEQ ID NOs: 335-352 (Table 4).

[0033]

[0030] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of any of SEQ ID NOs: 353-388 (Table 5). In some embodiments, a polypeptide comprises an amino acid sequence of any of SEQ ID NOs: 353-388 (Table 5).

[0034]

[0031] In some embodiments, a polypeptide binds specifically to fibroblast activation protein alpha (FAPa) with a Kd of 1x10-6 M or less.

[0035]

[0032] Some aspects relate to a protein conjugate comprising a polypeptide of the disclosure and a radiolabel. In some embodiments, a radiolabel is a radioisotope. In some embodiments, a radioisotope is selected from technetium-99m (Tc-99m), iodine-131 (1-131), iodine-123 (1-123), fluorine-18 (F- 18), carbon-11 (C-l l), gallium-67 (Ga-67), thallium-201 (Tl-201), indium-i l l (In-111), xenon-133 (Xe-133), samarium-153 (Sm-153), phosphorus-32 (P-32), strontium-89 (Sr-89), yttrium-90 (Y-90), rhenium-186 (Re-186), rhenium-188 (Re-188), lutetium-177 (Lu-177), holmium-166 (Ho-166), iodine-125 (1-125), cobalt-60 (Co-60), cesium-137 (Cs-137), iridium-192 (Ir-192), radium-223 (Ra-223), radium-226 (Ra- 226), promethium- 149 (Pm-149), molybdenum-99 (Mo-99), chromium-51 (Cr-51), sulfur-35 (S-35), sodium-24 (Na-24), copper-64 (Cu-64), iron-59 (Fe-59), zirconium-89 (Zr-89), copper-67 (Cu-67), manganese-52 (Mn-52), erbium-169 (Er-169), arsenic-74 (As-74), selenium-75 (Se-75), rubidium-82 (Rb-82), nitrogen-13 (N-13), oxygen-15 (0-15), calcium-47 (Ca-47), terbium-161 (Tb-161), yttrium-86 (Y-86), bromine-77 (Br-77), gadolinium- 153 (Gd-153), tin-117m (Sn-117m), lead-212 (Pb-212), bismuth-213 (Bi-213), scandium-47 (Sc-47), actinium-225 (Ac-225), krypton-81m (Kr-81m), gold-198 (Au-198), antimony-124 (Sb-124), americium-241 (Am-241), nickel-63 (Ni-63), technetium-95m (Tc- 95m), silver-111 (Ag-111), tantalum-180m (Ta-180m), germanium-68 (Ge-68), niobium-94 (Nb-94), terbium-149 (Tb-149), vanadium-48 (V-48), iodine-124 (1-124), praseodymium- 142 (Pr-142), copper-61 (Cu-61), bromine-76 (Br-76), ruthenium-106 (Ru-106), scandium-44 (Sc-44), yttrium-91 (Y-91), zirconium-88 (Zr-88), technetium-94m (Tc-94m), arsenic-76 (As-76), barium-133 (Ba-133), erbium-165 (Er-165), terbium-167 (Tb-167), xenon-127 (Xe-127), radon-222 (Rn-222), mercury-197 (Hg-197), radium-224 (Ra-224), actinium-227 (Ac-227), polonium-210 (Po-210), platinum-195m (Pt-195m), samarium-145 (Sm-145), europium-152 (Eu-152), neptunium-237 (Np-237), plutonium-239 (Pu-239), thorium-228 (Th-228), uranium-238 (U-238), yttrium-87 (Y-87), tin-121 (Sn-121), iodine-132 (1-132), cesium-134 (Cs-134), holmium-163 (Ho-163), krypton-85 (Kr-85), radon-220 (Rn-220), selenium-79 (Se-79), tellurium- 123m (Te-123m), palladium-103 (Pd-103), niobium-95 (Nb-95), hafnium-172 (Hf- 172), tungsten-181 (W-181), and californium-252 (Cf-252).

[0036]

[0033] Some aspects relate to a fusion protein comprising a polypeptide of the disclosure and at least one additional polypeptide.

[0037]

[0034] In some embodiments, at least one additional polypeptide is a half-life extension protein or molecule.

[0038]

[0035] In some embodiments, at least one additional polypeptide (e.g., a half-life extension protein) is a variant of human Stefin A that binds specifically to human serum albumin (HSA). Thus, provided herein, in further aspects, are polypeptide scaffolds, for example, AFFIMER® polypeptide scaffolds, based on variants of human Stefin A, which bind specifically to (HSA).

[0039]

[0036] Some aspects relate to a polypeptide comprising: a scaffold and a peptide comprising an amino acid sequence selected from the amino acid sequence of any of SEQ ID NOs: 389-440, 764, or 765 or SEQ ID NOs: 441-492, 766, or 767 (Table 6).

[0040]

[0037] Other aspects relate to a polypeptide comprising: a scaffold; a first peptide comprising an amino acid sequence selected from the amino acid sequence of any of SEQ ID NOs: 389-440, 764, or 765; and a second peptide comprising an amino acid sequence selected from the amino acid sequence of any of SEQ ID NOs: 441-492, 766, or 767 (Table 6).

[0041]

[0038] In some embodiments, a first peptide comprises the amino acid sequence of SEQ ID NO: 389 and a second peptide comprises the amino acid sequence of SEQ ID NO: 441. In some embodiments, a first peptide comprises the amino acid sequence of SEQ ID NO: 390 and a second peptide comprises the amino acid sequence of SEQ ID NO: 442. In some embodiments, a first peptide comprises the amino acid sequence of SEQ ID NO: 391 and a second peptide comprises the amino acid sequence of SEQ ID NO: 443. In some embodiments, a first peptide comprises the amino acid sequence of SEQ ID NO: 764 and a second peptide comprises the amino acid sequence of SEQ ID NO: 766; or a first peptide comprises the amino acid sequence of SEQ ID NO: 765 and a second peptide comprises the amino acid sequence of SEQ ID NO: 767.

[0042]

[0039] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of any of SEQ ID NOs: 493-546 (Table 7). In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of SEQ ID NO: 493 (HSA-1). In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of SEQ ID NO: 494 (HSA-2). In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of SEQ ID NO: 495 (HSA-3). In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of SEQ ID NO: 545 (HSA-53). In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of SEQ ID NO: 546 (HSA-54). In some embodiments, a polypeptide comprises the amino acid sequence of any of SEQ ID NOs: 493-546 (Table 7). In some embodiments, a polypeptide comprises the amino acid sequence of SEQ ID NO: 545 (HSA-53). In some embodiments, a polypeptide comprises the amino acid sequence of SEQ ID NO: 546 (HSA-54).

[0043]

[0040] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of any of SEQ ID NOs: 547-556 (Table 8). In some embodiments, a polypeptide comprises the amino acid sequence of any of SEQ ID NOs: SEQ ID NOs: 547-556 (Table 8).

[0044]

[0041] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of SEQ ID NO: 557 or 557 (Table 9). In some embodiments, a polypeptide comprises the amino acid sequence of any of SEQ ID NO: 557 or 557 (Table 9).

[0045]

[0042] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of any of SEQ ID NOs: 559-565 (Table

[0046] 10). In some embodiments, a polypeptide comprises the amino acid sequence of any of SEQ ID NOs: SEQ ID NOs: 559-565 (Table 10).

[0047]

[0043] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of any of SEQ ID NOs: 566-573 (Table

[0048] 11). In some embodiments, a polypeptide comprises the amino acid sequence of any of SEQ ID NOs: SEQ ID NOs: 566-573 (Table 11).

[0044] In some embodiments, a polypeptide binds specifically to human serum albumin (HSA) with a Kd of 1x106M or less.

[0049]

[0045] In some embodiments, a polypeptide comprises an amino acid sequence having at least 90%, at least 95%, or at least 98% identity to the amino acid sequence of any of SEQ ID NOs: 574-605, or 768- 782 (Table 12). In some embodiments, a polypeptide comprises the amino acid sequence of any of SEQ ID NOs: SEQ ID NOs: 574-605, or 768-782 (Table 12).

[0050]

[0046] In some embodiments, at least one additional polypeptide is capable of binding to a cell moiety.

[0051]

[0047] In some embodiments, a cell moiety is a tumor-associated antigen. Thus, in some embodiments, a polypeptide is considered “bispecific,” comprising a component (e.g., antibody or AFFIMER®) capable of binding to a cell moiety, such as s a tumor-associated antigen, and a component (e.g., anti-HSA AFFIMER®) capable of binding to HSA.

[0052]

[0048] In some embodiments, a half-life extension protein is selected from an Fc region of an antibody, transferrin, and albumin.

[0053]

[0049] In some embodiments, at least one additional polypeptide is a serum albumin-binding variant of a human Stefin A protein.

[0054]

[0050] Other aspects provide a protein conjugate comprising a polypeptide or the fusion protein of the disclosure and a moiety of interest.

[0055]

[0051] In some embodiments, a moiety of interest is selected from small molecule drugs or prodrugs.

[0056]

[0052] In some embodiments, a fusion protein or a protein conjugate further comprises a linker.

[0057]

[0053] Some aspects relate to a polynucleotide comprising an open reading frame encoding a polypeptide, a fusion protein, or a protein conjugate of the disclosure.

[0058]

[0054] Other aspects relate to a method comprising administering a polypeptide, a fusion protein, a protein conjugate, or a polynucleotide of the disclosure to a subject in need thereof.

[0059]

[0055] In some embodiments, a subject has a cancer.

[0060]

[0056] In some embodiments, a fusion protein, protein conjugate, or polynucleotide is used in a method for treating or diagnosing cancer.

[0061]

[0057] In some embodiments, a polypeptide, fusion protein, protein conjugate, or polynucleotide is used in the manufacture of a medicament for the treatment of cancer.

[0062]

[0058] Some aspects relate to a method comprising selecting a subject for treatment with the polypeptide, the fusion protein, the protein conjugate, or the polynucleotide of any preceding claim based on expression of FAPa and SEFN 11 in a tumor tissue sample from the subject, wherein expression of each of FAPa and SEFN 11 is higher than a respective threshold level.

[0063]

[0059] Other aspects relate to a method comprising assaying a tumor tissue sample from a subject for expression of FAPa and SEFN11 and selecting the subject for treatment with the polypeptide, the fusion protein, the protein conjugate, or the polynucleotide of any preceding claim when expression of each of FAPa and SEFN 11 is higher than a respective threshold level.

[0064]

[0060] In some embodiments, a tumor tissue is from a cancer listed in Table 14 or 15.

[0061] Some aspects relate to a polypeptide comprising: an amino acid sequence having at least 90% identity to the sequence of MGIPGGESEAKPATPEIQEIVDKVKPQEEEKTGETYGKEEAVQYKTQVX / TNYYIKVRAGDNKYM HLKVFKSLX2EDLVLTGYQVDKNKDDELTGF (SEQ ID NO: 2), wherein Xi is a first peptide comprising the amino acid sequence of any of SEQ ID NOs: 5-108 and X2 is a second peptide sequence comprising the amino acid sequence of any of SEQ ID NOs: 109-212.

[0065]

[0062] Other aspects relate to a polypeptide comprising: an amino acid sequence having at least 90% identity to the sequence of

[0066] MGIPGGLSEAKPATPEIQEIVDKVKPQLEEKTGETYGKLEAVQYKTQVX / TNYYIKVRAGDNKYM HLKVFKSLX2EDLVLTGYQVDKNKDDELTGF (SEQ ID NO: 2) modified to include one or more cysteine (C) substitution or addition, wherein Xi is a first peptide comprising the amino acid sequence of any of SEQ ID NOs: 5-108 and X2 is a second peptide sequence comprising the amino acid sequence of any of SEQ ID NOs: 109-212.

[0067]

[0063] Yet other aspects relate to a polypeptide comprising: an amino acid sequence having at least 90% identity to the sequence of MGIPGGLSEAKPATPEIQEIVDKVKPQLEEKTGETYGKLEAVQYKTQVX / TNYYIKVRAGDNKYM HLKVFKSLX2EDLVLTGYQVDKNKDDELTGF (SEQ ID NO: 2) modified to include one or more cysteine (C) substitution or addition, wherein Xi is a first peptide comprising the amino acid sequence of any of SEQ ID NOs: 389-440, 764, or 765, and X2 is a second peptide sequence comprising the amino acid sequence of any of SEQ ID NOs: 441-492, 766, or 767.

[0068] BRIEF DESCRIPTION OF THE DRAWINGS

[0069]

[0064] Non-limiting embodiments of the present disclosure will be described by way of example with reference to the accompanying figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the disclosure shown where illustration is not necessary to allow those of ordinary skill in the art to understand the disclosure. In the figures:

[0070]

[0065] FIG. 1 shows a PK analysis of AFFIMER® proteins. To determine the PK parameters for the half-life extending AFFIMER® proteins, protein samples were injected into HSA / hFcRn double knock in mice and samples collected at the indicated timepoints. The levels of AFFIMER® protein present at each time were then determined by ELISA. Data obtained and derived PK parameters are shown. HLE-FAP-2- FAP-l-H contains a cross-reactive mouse serum albumin and human serum albumin binding AFFIMER® protein (HLE) which can be used as a surrogate molecule for the HSA binding AFFIMER® proteins presented here, which do not bind mouse serum albumin.

[0071]

[0066] FIG. 2 shows size-exclusion chromatography (SEC) profiles of AFFIMER® constructs conjugated to 5 kDa PEG within Loop3, Loop7, and / or the Cterminus. The unconjugated parent proteins are also shown at the bottom of the panels. Single-domain FAP-2 (left panel) and two-domain FAP-2- FAP-l-H (right panel) exemplars are shown. A key to the right of each panel shows the location of the PEG conjugation sites: L3 - loop3, CT - Cterminus. lx, 2x, and 3xPEG conjugated species are shown.

[0072]

[0067] FIG. 3 shows size-exclusion chromatography (SEC) profiles of purified AFFIMER® conjugates containing either linker-payload 2 (LP2) or 1 (LP1), as indicated. The SEC profiles of the unconjugated AFFIMER® precursor (bottom peak) are also shown for FAP-2-CTCys-LP2 and FAP-2-FAP-1-H- CTCys-LP2.

[0073]

[0068] FIG. 4 shows cellular cytotoxicity assays using HEK293T cells (FAP-negative) or cells overexpressing FAP (HEK-FAP). Cells were incubated with the different EP14 AFFIMER® conjugates or unconjugated linker-payload, either alone or in the presence of hFAP or FAPi, as indicated, for 4 days in the presence of FBS substitute Panexin (which contains low levels of FAP). The warhead was also included as a positive control. The antiproliferative / cytotoxic effect of the compounds was measured as % inhibition relative to vehicle control.

[0074]

[0069] FIG. 5 shows cellular cytotoxicity assays using HEK293T cells (FAP-negative) or cells overexpressing FAP (HEK-FAP). Cells were incubated with the different EPl 6 AFFIMER® conjugates or unconjugated linker-payload, either alone or in the presence of hFAP or FAPi, as indicated, for 4 days in the presence of FBS substitute Panexin (which contains low levels of FAP). The warhead was also included as a positive control. The antiproliferative / cytotoxic effect of the compounds was measured as % inhibition relative to vehicle control.

[0075]

[0070] FIG. 6 shows cellular cytotoxicity assays using HEK293T cells (FAP-negative) or cells overexpressing FAP (HEK-FAP). Cells were incubated with the different EPl AFFIMER® conjugates or unconjugated linker-payload, either alone or in the presence of hFAP or FAPi, as indicated, for 4 days in the presence of FBS substitute Panexin (which contains low levels of FAP). The warhead was also included as a positive control. The antiproliferative / cytotoxic effect of the compounds was measured as % inhibition relative to vehicle control.

[0076]

[0071] FIG. 7 shows cellular cytotoxicity assays using HEK293T cells (FAP-negative) or cells overexpressing FAP (HEK-FAP). Cells were incubated with the different EP2 AFFIMER® conjugates or unconjugated linker-payload, either alone or in the presence of hFAP or FAPi, as indicated, for 4 days in the presence of FBS substitute Panexin (which contains low levels of FAP). The warhead was also included as a positive control. The antiproliferative / cytotoxic effect of the compounds was measured as % inhibition relative to vehicle control.

[0077]

[0072] FIG. 8 shows cellular cytotoxicity of FAP-2-FAP-1-H AFFIMER® proteins conjugated to different linker-payloads at the C terminus. HEK293T cells (FAP-negative) were incubated with the different AFFIMER® conjugates, either alone or in the presence of hFAP or FAPi, as indicated, for 3 days in the presence of FBS substitute Panexin (which contains low levels of FAP). The warhead was also included as a positive control. The antiproliferative / cytotoxic effect of the molecules was measured as % inhibition relative to vehicle control.

[0073] FIG. 9 shows cellular cytotoxicity of FAP-2-FAP-1-H AFFIMER® proteins conjugated to LP2 via Cys residues engineered at the N terminus (NT), helical linker LN, and / or the C terminus (CT). DAR 1 , DAR 2 and DAR 3 exemplars are shown. HEK293T cells (FAP-negative) were incubated with the different AFFIMER® conjugates, either alone or in the presence of hFAP or FAPi, as indicated, for 3 days in the presence of FBS substitute Panexin (which contains low levels of FAP). The warhead was also included as a positive control. The antiproliferative / cytotoxic effect of the molecules was measured as % inhibition relative to vehicle control.

[0078]

[0074] FIG.10 shows HEK293T cell cytotoxicity profiles for AFFIMER® fusion proteins conjugated to LP2 containing combinations of both FAP-binding and HSA-binding AFFIMER® domains. HEK293T cells (FAP-negative) were incubated with the different AFFIMER® conjugates, either alone or in the presence of hFAP or FAPi, as indicated, for 3 days in the presence of FBS substitute Panexin (which contains low levels of FAP). The warhead was also included as a positive control. The antiproliferative / cytotoxic effect of the molecules was measured as % inhibition relative to vehicle control.

[0079]

[0075] FIG. 11 shows co-culture assay using MiaPaCa2-GFP pancreatic cancer cells (FAP-negative) in the presence (co-culture) or absence (mono-culture) of human pancreatic stellate (hPSC) stromal cells. Cells were incubated with lOnM AFFIMER® conjugates (FAP-2-FAP-l-H-L3Cys-LP2 or FAP-2-FAP- l-H-L3Cys-LPl) for 5 days in the presence of FBS substitute Panexin (which contains low levels of FAP). The warhead was also included as a positive control. The antiproliferative / cytotoxic effect of the compounds was measured as % GFP positive cells using Incucyte.

[0080]

[0076] FIG. 12 shows co-culture assays using LS174T-GFP colorectal adenocarcinoma cells (FAP- negative) in the presence (co-culture) or absence (mono-culture) of human colonic fibroblast (HCoF) cells. Cells were incubated with different LP2 AFFIMER® conjugates, either alone or in the presence of hFAP or FAPi, as indicated, for 4 days in the presence of FBS substitute Panexin (which contains low levels of FAP). The warhead was also included as a positive control. The antiproliferative / cytotoxic effect of the compounds was measured as % GFP positive cells using Incucyte.

[0081]

[0077] FIG. 13 shows cytotoxicity profiles of FAP-negative MDA-MB-231-GFP cells as 3D spheroid mono-culture (left panels) or co-culture with FAP-expressing human mammary fibroblast (HMF) cells (right panels) after 7-day incubation with different linker payload (LP2, LP10, LP11, or LP12) AFFIMER® conjugates, with or without hFAP or FAPi, in complete MammoCult medium (chemically defined with no exogenous FAP) supplemented with collagen I, heparin and hydrocortisone. Warhead was included as positive control. Tumour spheroid specific cytotoxicity was measured as % inhibition relative to vehicle control using GFP fluorescence and the Incucyte.

[0082]

[0078] FIG. 14 shows an in vivo tumour uptake study for AFFIMER® conjugates. Mice implanted with a CDX model of LS174T cells expressing human FAP, were treated with a panel of half-life extension AFFIMER® conjugates. Levels of released warhead in tumour and plasma measured by LC / MS, are shown. DETAILED DESCRIPTION

[0083]

[0079] AFFIMER® technology is a novel class of biological, based on the naturally occurring human protein Stefin A, which enables the development of next-generation biotherapeutics. These proteins are smaller than antibodies meaning that they potentially have better tissue penetration advantages in solid tumors. This, combined with exquisite specificity, strong stability, and high expression, confers excellent drug-like properties to AFFIMER® molecules (e.g., AFFIMER® polypeptides, and / or fusions and / or conjugates comprising AFFIMER® polypeptides). Moreover, the PK / PD of therapeutic AFFIMER® molecules can be tuned using, for example, AFFIMER XT®, a serum albumin-binding AFFIMER® molecule with half-life extension properties or using AFFIMER® molecule-Fc fusions. AFFIMER® molecules can also be genetically fused to each other to form multi-specific therapies, or to other proteins, such as the C-terminus of an antibody, to generate bispecific biobetter formats.

[0084]

[0080] The AFFIMER® molecules provided herein are based on a human Stefin A scaffold that has been modified to prevent amino terminal acetylation / oxidation and increase thermal stability. Thus, various aspects herein relate to polypeptides comprising a scaffold that comprises a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1, wherein the scaffold sequence includes (a) an insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 and (b) a mutation at an amino acid position corresponding to N32 of the amino acid sequence of SEQ ID NO: 1 and a heterologous peptide. In some embodiments, the insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 assists in N-terminal methionine cleavage, reducing N-terminal heterogeneity (e.g., presence or absence of methionine and / or acetylation of methionine).

[0085]

[0081] The polypeptides provided herein, in some aspects, bind to fibroblast activation protein (FAP), which is a serine protease enzyme that plays a significant role in tissue remodeling, wound healing, and fibrosis. It belongs to the dipeptidyl peptidase family of proteases and has both enzymatic and non- enzymatic functions. FAP is a type II integral membrane glycoprotein composed of 760 amino acids, with a large extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. It has both dipeptidyl peptidase and endopeptidase activities, meaning it can cleave proline-containing peptides after the second amino acid and degrade extracellular matrix (ECM) components, respectively. This dual functionality is crucial for its role in tissue remodeling and cell signaling.

[0086]

[0082] FAP is expressed in various tissues and cell types under specific conditions. For example, FAP is highly expressed in activated fibroblasts, which are involved in wound healing and fibrosis. In normal tissue, fibroblasts usually do not express FAP, but upon activation during tissue injury or disease states, they start expressing this protein. FAP is notably upregulated in the stromal fibroblasts of many epithelial cancers, including breast, colorectal, lung, and pancreatic cancers. Its expression is associated with cancer-associated fibroblasts (CAFs), contributing to tumor growth, invasion, and metastasis by remodeling the ECM and promoting a supportive environment for cancer cells. In fibrotic conditions such as liver cirrhosis, pulmonary fibrosis, and cardiac fibrosis, FAP expression is upregulated. Activated fibroblasts and myofibroblasts in these diseases express FAP, contributing to the excessive deposition of ECM and tissue scarring. FAP expression is also observed in inflammatory conditions where tissue remodeling and repair are ongoing, such as in rheumatoid arthritis and chronic wounds.

[0087]

[0083] In some embodiments, the polypeptides of the disclosure bind to FAPa with a Kd of lxlO-6M or less, Kd of lxlO-7M or less, Kd of lxlO-8M or less, Kd of lxlO-9M or less, or a Kd of lxlO“loM or less. In some embodiments, a polypeptide of the disclosure binds to FAPa with a Kd of lxlO“6M or less. The equilibrium dissociation constant (Kd) is a measure of the affinity between two molecules, such as an AFFIMER® polypeptide and its target antigen, a ligand and a receptor, or an enzyme and its substrate. It represents the concentration of a molecule at which half of the available binding sites are occupied. Smaller equilibrium dissociation constants represent more tightly bound molecules; that is, a higher the affinity between two molecules. A Kd can be measured by any method known in the art, for example, with surface plasmon resonance (e.g., using the BIACORE™ system).

[0088]

[0084] In some embodiments, the polypeptides of the disclosure that bind to FAP are used in the treatment of cancer or fibrosis. In other embodiments, the polypeptides are used to visualize and monitor fibrotic activity and tumor stroma.

[0089]

[0085] The polypeptides provided herein, in some aspects, bind to human serum albumin (HSA) or include an additional polypeptide that binds to HSA, which is the most abundant protein in human blood plasma, constituting about 50-60% of the total plasma protein content. It is produced by the liver and has a molecular weight of approximately 66.5 kDa. HSA plays several crucial roles in maintaining physiological functions and homeostasis. HSA is a single-chain polypeptide composed of 585 amino acids. It has a heart-shaped structure with three homologous domains, each containing several alphahelices. HSA is highly soluble in water and can bind to various ligands, including fatty acids, hormones, drugs, and metabolites. HSA serves as a carrier protein in vivo, binding and transporting various endogenous and exogenous substances. Due at least in part to the binding properties of the binding properties HSA, the polypeptides that specifically bind to HSA, as provided herein, can be used to improve the pharmacokinetics and stability of drugs to which the polypeptides are fused or conjugated.

[0090]

[0086] In some embodiments, the polypeptides of the disclosure bind to HSA with a Kd of lxlO-6M or less, Kd of lxlO-7M or less, Kd of lxl0-8M or less, Kd of lxlO-9M or less, or a Kd of IxlO-lOM or less. In some embodiments, a polypeptide of the disclosure binds to HSA with a Kd of lxlO-6M or less.

[0091] Polypeptides

[0092]

[0087] Polypeptides (which include peptides and proteins) are polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The term also encompasses an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing at least one analog of an amino acid (including, for example, unnatural amino acids), as well as other modifications known in the art.

[0088] For the most part, the amino acids used in the application of this disclosure are those naturally occurring amino acids found in proteins, or the naturally occurring anabolic or catabolic products of such amino acids which contain amino and carboxyl groups. Particularly suitable amino acid side chains include side chains selected from those of the following amino acids: glycine, alanine, valine, cysteine, leucine, isoleucine, serine, threonine, methionine, glutamic acid, aspartic acid, glutamine, asparagine, lysine, arginine, proline, histidine, phenylalanine, tyrosine, and tryptophan, and those amino acids and amino acid analogs which have been identified as constituents of peptidylglycan bacterial cell walls.

[0093]

[0089] Amino acid residues having “basic sidechains” include arginine, lysine, and histidine. Amino acid residues having “acidic sidechains” include glutamic acid and aspartic acid. Amino acid residues having “neutral polar sidechains” include serine, threonine, asparagine, glutamine, cysteine, and tyrosine. Amino acid residues having “neutral non-polar sidechains” include glycine, alanine, valine, isoleucine, leucine, methionine, proline, tryptophan, and phenylalanine. Amino acid residues having “non-polar aliphatic sidechains” include glycine, alanine, valine, isoleucine, and leucine. Amino acid residues having “hydrophobic sidechains” include alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan. Amino acid residues having “small hydrophobic sidechains” include alanine and valine. Amino acid residues having “aromatic sidechains” include tyrosine, tryptophan, and phenylalanine.

[0094] Scaffolds

[0095]

[0090] A protein scaffold includes a framework or structure that provides a stable platform for displaying functional protein domains or peptides, for example. These scaffolds are typically engineered proteins that have a robust and stable tertiary structure, allowing them to tolerate insertions, deletions, or substitutions without losing their overall fold and stability.

[0096]

[0091] In some embodiments, a scaffold comprises a sequence having at least 90% (e.g., at least 95%, at least 96%, at least 97%, or at least 98%) identity to the amino acid sequence of SEQ ID NO: 1 (human Stefin A):

[0097] MIPGGLSEAK PATPEIQEIV DKVKPQLEEK TNETYGKLEA VQYKTQVVAG TNYYIKVRAG DNKYMHLKVF KSLPGQNEDL VLTGYQVDKN KDDELTGF ( SEQ ID NO : 1 )

[0098]

[0092] Human Stefin A (also known as Cystatin A) is a type of cystatin, which is a family of cysteine protease inhibitors. These proteins play a critical role in regulating protease activity within cells, thereby helping to control protein degradation and protect tissues from damage caused by proteolytic enzymes. Human Stefin A is a small protein with a molecular weight of approximately 11 kDa, and it typically has about 98 amino acids.

[0099]

[0093] The polypeptides provided herein include a scaffold that includes a modified version of human Stefin A. Such polypeptides comprising a modified version of human Stefin A as well as one or two, preferably two, heterologous peptides are referred to herein as AFFIMER® polypeptides. AFFIMER® polypeptides are small, engineered proteins designed to bind specifically to target molecules. They are derived from human Stefin A scaffold proteins and have distinct loop structures that confer their binding properties. The different loop structures of an AFFIMER® polypeptide, based on their design and origin, typically include two variable “loop” structures. A Variable Loop 2 (VL2) is one of the primary loops responsible for binding specificity. It is engineered to interact with the target molecule through various amino acid substitutions, providing a high degree of diversity and specificity. A Variable Loop 4 (VL4) also contributes significantly to the binding interaction. The combination of VL2 and VL4 provides the structural diversity often needed for high-affinity binding to a wide range of targets. While not loops per se, the framework regions (collectively the scaffold) support the variable loops structurally. These regions are typically more conserved and provide a stable scaffold to present the variable loops in the correct orientation for target binding.

[0100]

[0094] In some embodiments, a scaffold provided herein includes a modification that prevents amino terminal acetylation / oxidation relative to the naturally occurring human Stefin A protein. In some embodiments, a scaffold includes a modification that increases thermal stability (e.g., by at least 20%, at least 30%, at least 40%, or at least 50%) of the scaffold (or of a polypeptide containing the scaffold), relative to the naturally occurring human Stefin A protein.

[0101]

[0095] In some embodiments, a scaffold (or scaffold sequence, i.e., an amino acid sequence within a scaffold) includes (a) an insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 and (b) a mutation at an amino acid position corresponding to N32 of the amino acid sequence of SEQ ID NO: 1, as shown in the amino acid sequence of SEQ ID NO: 2:

[0102] MGIPGGLSEA KPATPEIQEI VDKVKPQLEE KTGETYGKLE AVQYKTQV-X1-TN YYIKVRAGDN KYMHLKVFKS L-X2-EDLVLTGYQ VDKNKDDELT GF ( SEQ ID NO : 2 ) , wherein XI is any heterologous peptide (e.g., having a length of about 4 to 16 amino acids) and X2 is any heterologous peptide (e.g., having a length of about 4 to 16 amino acids).

[0103]

[0096] In some embodiments, a polypeptide comprises a scaffold comprising (a) a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1, wherein the scaffold sequence includes (i) an insertion of an amino acid (e.g., glycine) between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 and (ii) a mutation at an amino acid position corresponding to N32 (e.g., N32G) of the amino acid sequence of SEQ ID NO: 1, and (b) a heterologous peptide (e.g., two heterologous peptides).

[0104]

[0097] In some embodiments, a polypeptide comprises a scaffold comprising (a) a sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 1, wherein the scaffold sequence includes (i) an insertion of an amino acid (e.g., glycine) between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 and (ii) a mutation at an amino acid position corresponding to N32 (e.g., N32G) of the amino acid sequence of SEQ ID NO: 1, and (b) a heterologous peptide (e.g., two heterologous peptides).

[0105]

[0098] In some embodiments, a polypeptide comprises a scaffold comprising (a) a sequence having at least 98% identity to the amino acid sequence of SEQ ID NO: 1, wherein the scaffold sequence includes (i) an insertion of an amino acid (e.g., glycine) between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 and (ii) a mutation at an amino acid position corresponding to N32 (e.g., N32G) of the amino acid sequence of SEQ ID NO: 1, and (b) a heterologous peptide (e.g., two heterologous peptides).

[0106]

[0099] In some embodiments, the insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 is a glycine (G). In some embodiments, the insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 is an alanine (A). In some embodiments, the insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 is a serine (S). In some embodiments, the insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 is a proline (P). In some embodiments, the insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 is a threonine (T). In some embodiments, the mutation at an amino acid position corresponding to N32 of the amino acid sequence of SEQ ID NO: 1 is an N32G mutation (i.e., asparagine to glycine).

[0107]

[0100] In some embodiments, the sequence of a scaffold has at least 95% identity to the amino acid sequence of SEQ ID NO: 2. In some embodiments, a sequence of a scaffold has 95% identity to about 98% identity to the amino acid sequence of SEQ ID NO: 2. In some embodiments, a sequence of a scaffold has about 98% identity to the amino acid sequence of SEQ ID NO: 2. In some embodiments, a scaffold comprises the amino acid sequence of SEQ ID NO: 2. In some embodiments, a scaffold consists of the amino acid sequence of SEQ ID NO: 2.

[0108]

[0101] Percent identity in the context of DNA, RNA, or protein sequences refers to the percentage of positions (nucleotides in DNA / RNA or amino acids in proteins) that are identical in two aligned sequences when compared. Global and local alignment are two methods used in bioinformatics to align sequences, such as DNA, RNA, or proteins, to identify regions of similarity that may indicate functional, structural, or evolutionary relationships among the sequences. A global alignment aligns two sequences from beginning to end, attempting to align every residue in each sequence. This method typically uses the Needleman-Wunsch algorithm and is ideal for sequences of roughly equal size and when you expect that the sequences are similar over their entire length. A global alignment can introduce gaps as necessary to align as much of the sequences as possible. A local alignment finds the most similar subsequence(s) between two sequences. It does not require that the entirety of either sequence align. This method is typically implemented using the Smith- Waterman algorithm and is ideal for sequences that may have highly similar regions or motifs within otherwise dissimilar sequences.

[0109]

[0102] Unless stated otherwise, “identity” between two sequences is calculated using a global (end-to- end) alignment.

[0110]

[0103] In some embodiments, a scaffold further comprises a cysteine. In some embodiments, a cysteine is introduced at the C-terminus of the scaffold. In some embodiments, a cysteine is introduced at the N- terminus of the scaffold. In some embodiments, a cysteine is introduced between two heterologous proteins peptides (e.g., between a variable Loop 2 peptide and a variable Loop 4 peptide, e.g., between positions T51 and L73 of the amino acid sequence of SEQ ID NO: 1, or between positions T49 and L71 of the amino acid sequence of SEQ ID NO: 4). In some embodiments, the cysteine is introduced at a position in the scaffold corresponding to position D61 of the amino acid sequence of SEQ ID NO: 1. In some embodiments, two cysteines are introduced: a first cysteine at the C-terminus of the scaffold and a second cysteine at a position corresponding to the region between positions T51 and L73 of the amino acid sequence of SEQ ID NO: 1 (e.g., a position corresponding to position D61 of the amino acid sequence of SEQ ID NO: 1).

[0111]

[0104] In some embodiments, a scaffold comprises multiple cysteines, for example at least 2, 3, 4, or 5 cysteines. In some embodiments, a scaffold comprises a C terminal cysteine and a cysteine in Loop 3 of the scaffold (between the Loop 2 and Loop 4 heterologous peptide sequences). In some embodiments, a scaffold comprises an N terminal cysteine and a cysteine in Loop 3 of the scaffold (between the Loop 2 and Loop 4 heterologous peptide sequences). In some embodiments, such as those in which an AEEIMER® molecule comprises two (or more) AEEIMER® polypeptides (e.g., an in-line fusion of two monomors), each of the AEEIMER® polypeptides comprise a (one or more) cysteine, for example, in a Loop 3 region, at or near the N-terminus, and / or at or near the C terminus of one or more AFFIMER® polypeptides (e.g., monomers) within an AFFIMER® molecule (e.g., in-line fusion comprising multiple monomers). Herein, “Loop 3” refers to the framework-like region of an AFFIMER® polypeptide located between the variable Loop 2 and Loop 4 peptides, which are typically designed specifically to a target molecule of interest (e.g., FAP). For AFFIMER® molecules that include multiple AFFIMER® polypeptides may include a cysteine in Loop 3 of a first AFFIMER® polypeptide and in Loop 3 in a second AFFIMER® polypeptide. Herein, the Loop 3 of the second AFFIMER® polypeptide may also be referred to as Loop 7 of the AFFIMER® molecule.

[0112]

[0105] A cysteine, in some embodiments, is used for conjugation (e.g., in the context of protein conjugates, described below), for example, to one or more agent, such as one or more small molecule drugs (e.g., cytotoxic drugs). The use of cysteine for conjugation in AFFIMER® molecules also sets them apart from antibodies. In antibodies, cysteines are often part of the framework and / or variable regions of the antibodies, required to create and maintain the structure of the antibody (e.g., through disulfide bonds). Therefore, the use of cysteine conjugation in antibodies may cause structural, solubility, and / or other issues because key structural cysteine residues may be reduced. In contrast, AFFIMER® molecules are not limited in this manner and have significantly more flexibility with respect to conjugation.

[0113]

[0106] In some embodiments, an AFFIMER® molecule comprises multiple cysteines such that multiple agents (e.g., small molecule drug payloads) can be conjugated to the AFFIMER® molecule. Thus, a single AFFIMER® molecule (either a monomer AFFIMER® polypeptide or a fusion of multiple AFFIMER® polypeptides) can comprise multiple agents of the same type or multiple different types of agents.

[0114] Heterologous Peptides

[0107] The polypeptides provided herein include one or more heterologous peptide (heterologous to the modified human Stefin A scaffold) that enables the polypeptides to bind to a target with high affinity and exquisite selectivity. A heterologous peptide may be referred to herein as a variable Loop 2 peptide (comprising a variable Loop 2 sequence) or a variable Loop 4 peptide (comprising a Loop 4 sequence). A heterologous peptide is considered an “insertion” in a scaffold sequence, for example, of an AFFIMER® polypeptide such that when the percent identity of the amino acid sequence of a scaffold is calculated relative to human Stefin A (wild-type human Stefin A), the heterologous peptide (or heterologous peptides) is excluded from the calculation. Thus, a polypeptide comprising a scaffold comprising a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1 does not factor a heterologous peptide into the percent identity calculation. For example, consider an AFFIMER® polypeptide having the following full-length sequence:

[0115] MGIPGGLSEA KPATPEIQEI VDKVKPQLEE KTGETYGKLE AVQYKTQVXX XXXXXXXTNY YIKVRAGDNK YMHLKVFKSL XXXXXXXXXE DLVLTGYQVD KNKDDELTGF ( SEQ ID NO : 3 )

[0116]

[0108] This sequence includes a scaffold sequence (SEQ ID NO: 4) as well as two heterologous peptide sequences (each designated “XXXXXXXXX”), each inserted into the scaffold sequence.

[0117] MGIPGGLSEA KPATPEIQEI VDKVKPQLEE KTGETYGKLE AVQYKTQVTN YYIKVRAGDN KYMHLKVFKS LEDLVLTGYQ VDKNKDDELTGF ( SEQ ID NO : 4 )

[0118] The scaffold sequence (SEQ ID NO: 4) of the AFFIMER® polypeptide (SEQ ID NO: 3) has 90% identity to the scaffold sequence of human Stefin A (SEQ ID NO: 1): M-IPGGLSEAKPATPEIQEIVDKVKPQLEEKTNETYGKLEAVQYKTQVVAGTNYYIKVRA MGIPGGLSEAKPATPEIQEIVDKVKPQLEEKTGETYGKLEAVQYKTQV - TNYYIKVRA

[0119] * ****************************** *************** ** ** ** ** *

[0120] GDNKYMHLKVFKSLPGQNEDLVLTGYQVDKNKDDELTGF ( SEQ ID NO : 1 ) GDNKYMHLKVFKSL - EDLVLTGYQVDKNKDDELTGF ( SEQ ID NO : 4 )

[0121] * *** ** ** ** ** ** ** ** ** ** ** ** ** ** ** ** *

[0122]

[0109] In some embodiments, a heterologous peptide (e.g., an AFFIMER® variable Loop 2 peptide and / or an AFFIMER® variable Loop 4 peptide) comprises an amino acid sequence having a length of about 4 to about 20 amino acids. For example, a heterologous peptide can comprise an amino acid sequence having a length of about 8 to about 16 amino acids. In some embodiments, a heterologous peptide comprises an amino acid sequence having a length of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids. In some embodiments, a heterologous peptide comprises an amino acid sequence having a length of 9 amino acids. In some embodiments, a heterologous peptide comprises an amino acid sequence having a length of 12 amino acids. In some embodiments, a heterologous peptide comprises an amino acid sequence having a length of 15 amino acids. In some embodiments, a heterologous peptide comprises an amino acid sequence having a length of 4 to 12, 5 to 12, 6 to 12, 4 to 10, 6 to 10, 8 to 10, 5 to 15, 6 to 15, 7 to 15, 5 to 13, 7 to 13, 9 to 13, 11 to 13, 8 to 18, 9 to 18, 10 to 18, 10 to 16, 12 to 16, or 14 to 16 amino acids. [HO] In some embodiments, an AFFIMER® variable Loop 2 peptide comprises an amino acid sequence having a length of 4 to 12, 5 to 12, 6 to 12, 4 to 10, 6 to 10, or 8 to 10 amino acids and an AFFIMER® variable Loop 4 peptide comprises an amino acid sequence having a length of 4 to 12, 5 to 12, 6 to 12, 4 to 10, 6 to 10, or 8 to 10 amino acids. In some embodiments, an AFFIMER® variable Loop 2 peptide comprises an amino acid sequence having a length of 9 amino acids and an AFFIMER® variable Loop 4 peptide comprises an amino acid sequence having a length of 9 amino acids. In some embodiments, an AFFIMER® variable Loop 2 peptide comprises an amino acid sequence having a length of 9 amino acids and the polypeptide does not comprise an AFFIMER® variable Loop 4 peptide.

[0123]

[0111] In some embodiments, an AFFIMER® variable Loop 2 peptide comprises an amino acid sequence having a length of 5 to 15, 6 to 15, 7 to 15, 5 to 13, 7 to 13, 9 to 13, or 11 to 13 amino acids and an AFFIMER® variable Loop 4 peptide comprises an amino acid sequence having a length of 5 to 15, 6 to 15, 7 to 15, 5 to 13, 7 to 13, 9 to 13, or 11 to 13 amino acids. In some embodiments, an AFFIMER® variable Loop 2 peptide comprises an amino acid sequence having a length of 12 amino acids and an AFFIMER® variable Loop 4 peptide comprises an amino acid sequence having a length of 12 amino acids.

[0124]

[0112] In some embodiments, an AFFIMER® variable Loop 2 peptide comprises an amino acid sequence having a length of 8 to 18, 9 to 18, 10 to 18, 10 to 16, 12 to 16, or 14 to 16 amino acids and an AFFIMER® variable Loop 4 peptide comprises an amino acid sequence having a length of 8 to 18, 9 to 18, 10 to 18, 10 to 16, 12 to 16, or 14 to 16 amino acids. In some embodiments, an AFFIMER® variable Loop 2 peptide comprises an amino acid sequence having a length of 15 amino acids and an AFFIMER® variable Loop 4 peptide comprises an amino acid sequence having a length of 15 amino acids.

[0125]

[0113] In some embodiments, a heterologous peptide (e.g., an AFFIMER® variable Loop 2 peptide) is located in a sequence of a scaffold between amino acid positions corresponding to positions V47 and T51 of the amino acid sequence of SEQ ID NO: 1. As shown in the above alignment, positions V47 and T51 of the amino acid sequence of SEQ ID NO: 1 correspond respectively to positions V48 and T49 of the amino acid sequence of SEQ ID NO: 4, which is the scaffold sequence (minus any heterologous peptide) of, for example, an AFFIMER polypeptide comprising the amino acid sequence of SEQ ID NO: 2, wherein each of XI and X2 is an independent heterologous peptide. Thus, in some embodiments, a heterologous peptide (e.g., an AFFIMER® variable Loop 2 peptide) is located in a sequence of a scaffold between amino acid positions corresponding to positions V48 and T49 of the amino acid sequence of SEQ ID NO: 4.

[0126]

[0114] In some embodiments, a heterologous peptide (e.g., an AFFIMER® variable Loop 4 peptide) is located in a sequence of a scaffold between amino acid positions corresponding to positions L73 and E78 of the amino acid sequence of SEQ ID NO: 1. As shown in the above alignment, positions L73 and E78 of the amino acid sequence of SEQ ID NO: 1 correspond respectively to positions L71 and E72 of the amino acid sequence of SEQ ID NO: 4, which is the scaffold sequence (minus any heterologous peptide) of, for example, an AFFIMER® polypeptide comprising the amino acid sequence of SEQ ID NO: 2, wherein each of XI and X2 is an independent heterologous peptide. Thus, in some embodiments, a heterologous peptide (e.g., an AFFIMER® variable Loop 4 peptide) is located in a sequence of a scaffold between amino acid positions corresponding to positions L71 and E72 of the amino acid sequence of SEQ ID NO: 4.

[0127]

[0115] In some embodiments, a polypeptide comprises a scaffold comprising the amino acid sequence of SEQ ID NO: 2, wherein XI is a heterologous peptide having a length of 8 amino acids, and X2 is a heterologous peptide having a length of 8 amino acids. In some embodiments, a polypeptide comprises a scaffold comprising the amino acid sequence of SEQ ID NO: 2, wherein XI is a heterologous peptide having a length of 9 amino acids, and X2 is a heterologous peptide having a length of 9 amino acids. In some embodiments, a polypeptide comprises a scaffold comprising the amino acid sequence of SEQ ID NO: 2, wherein XI is a heterologous peptide having a length of 9 amino acids, and X2 is a heterologous peptide having a length of 0 amino acids (i.e., there is no second heterologous peptide). In some embodiments, a polypeptide comprises a scaffold comprising the amino acid sequence of SEQ ID NO: 2, wherein XI is a heterologous peptide having a length of 10 amino acids, and X2 is a heterologous peptide having a length of 10 amino acids. In some embodiments, a polypeptide comprises a scaffold comprising the amino acid sequence of SEQ ID NO: 2, wherein XI is a heterologous peptide having a length of 12 amino acids, and X2 is a heterologous peptide having a length of 12 amino acids. In some embodiments, a polypeptide comprises a scaffold comprising the amino acid sequence of SEQ ID NO: 2, wherein XI is a heterologous peptide having a length of 15 amino acids, and X2 is a heterologous peptide having a length of 15 amino acids.

[0128]

[0116] Exemplary variable Loop 2 sequences and variable Loop 4 sequences of polypeptides that bind to FAP are provided in Table 1 below.

[0129] Table 1. Exemplary FAP Binder Loop Sequences

[0117] In some embodiments, a heterologous peptide comprises a sequence selected from the amino acid sequence of any one of SEQ ID NOs: 5-212.

[0130]

[0118] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Eoop 2 peptide comprising the amino acid sequence of SEQ ID NO: 5 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 109.

[0131]

[0119] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 6 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 110.

[0132]

[0120] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 7 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 111.

[0133]

[0121] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 8 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 112.

[0134]

[0122] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 9 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 113.

[0135]

[0123] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 10 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 114.

[0136]

[0124] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 11 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 115.

[0137]

[0125] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 12 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 116.

[0138]

[0126] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 13 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 117.

[0139]

[0127] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 14 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 118.

[0140]

[0128] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 15 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 119.

[0129] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 16 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 120.

[0141]

[0130] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 17 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 121.

[0142]

[0131] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 18 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 122.

[0143]

[0132] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 19 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 123.

[0144]

[0133] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 20 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 124.

[0145]

[0134] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 21 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 125.

[0146]

[0135] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 22 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 126.

[0147]

[0136] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 23 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 127.

[0148]

[0137] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 24 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 128.

[0149]

[0138] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 25 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 129.

[0150]

[0139] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 26 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 130.

[0151]

[0140] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 27 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 131.

[0141] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 28 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 132.

[0152]

[0142] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 29 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 133.

[0153]

[0143] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 30 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 134.

[0154]

[0144] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 31 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 135.

[0155]

[0145] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 32 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 136.

[0156]

[0146] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 33 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 137.

[0157]

[0147] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 34 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 138.

[0158]

[0148] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 35 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 139.

[0159]

[0149] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 36 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 140.

[0160]

[0150] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 37 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 141.

[0161]

[0151] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 38 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 142.

[0162]

[0152] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 39 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 143.

[0153] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 40 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 144.

[0163]

[0154] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 41 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 145.

[0164]

[0155] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 42 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 146.

[0165]

[0156] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 43 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 147.

[0166]

[0157] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 44 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 148.

[0167]

[0158] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 45 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 149.

[0168]

[0159] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 46 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 150.

[0169]

[0160] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 47 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 151.

[0170]

[0161] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 48 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 152.

[0171]

[0162] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 49 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 153.

[0172]

[0163] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 50 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 154.

[0173]

[0164] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 51 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 155.

[0165] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 52 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 156.

[0174]

[0166] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 53 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 157.

[0175]

[0167] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 54 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 158.

[0176]

[0168] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 55 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 159.

[0177]

[0169] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 56 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 160.

[0178]

[0170] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 57 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 161.

[0179]

[0171] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 58 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 162.

[0180]

[0172] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 59 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 163.

[0181]

[0173] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 60 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 164.

[0182]

[0174] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 61 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 165.

[0183]

[0175] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 62 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 166.

[0184]

[0176] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 63 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 167.

[0177] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 64 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 168.

[0185]

[0178] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 65 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 169.

[0186]

[0179] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 66 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 170.

[0187]

[0180] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 67 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 171.

[0188]

[0181] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 68 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 172.

[0189]

[0182] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 69 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 173.

[0190]

[0183] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 70 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 174.

[0191]

[0184] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 71 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 175.

[0192]

[0185] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 72 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 176.

[0193]

[0186] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 73 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 177.

[0194]

[0187] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 74 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 178.

[0195]

[0188] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 75 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 179.

[0189] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 76 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 180.

[0196]

[0190] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 77 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 181.

[0197]

[0191] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 78 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 182.

[0198]

[0192] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 79 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 183.

[0199]

[0193] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 80 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 184.

[0200]

[0194] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 81 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 185.

[0201]

[0195] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 82 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 186.

[0202]

[0196] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 83 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 187.

[0203]

[0197] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 84 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 188.

[0204]

[0198] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 85 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 189.

[0205]

[0199] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 86 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 190.

[0206]

[0200] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 87 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 191.

[0201] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 88 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 192.

[0207]

[0202] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 89 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 193.

[0208]

[0203] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 90 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 194.

[0209]

[0204] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 91 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 195.

[0210]

[0205] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 92 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 196.

[0211]

[0206] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 93 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 197.

[0212]

[0207] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 94 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 198.

[0213]

[0208] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 95 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 199.

[0214]

[0209] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 96 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 200.

[0215]

[0210] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 97 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 201.

[0216]

[0211] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 98 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 202.

[0217]

[0212] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 99 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 203.

[0213] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 100 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 204.

[0218]

[0214] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 101 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 205.

[0219]

[0215] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 102 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 206.

[0220]

[0216] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 103 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 207.

[0221]

[0217] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 104 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 208.

[0222]

[0218] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 105 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 209.

[0223]

[0219] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 106 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 210.

[0224]

[0220] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 107 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 211.

[0225]

[0221] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 108 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 212.

[0226]

[0222] Exemplary polypeptide sequences described herein are provided in Tables 2-5.

[0227] Table 2. Exemplary FAP Binder Monomer Protein Sequences

[0228] Table 3. Exemplary FAP Binder Dimer Protein Sequences

[0229] Table 4. Exemplary FAP Binder Monomer Protein Sequences with Cysteine Modification

[0230] Table 5. Exemplary FAP Binder Dimer Protein Sequences with Cysteine Modification

[0231] Rigid (R) Linker=AEAAAKEAAAKEAAAKEAAAKEAAAKEAAAK (SEQ ID NO: 606)

[0232] Flexible (F) Linker=GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSG (SEQ ID NO: 607)

[0233] L3Cys=Loop 3 Cysteine (for conjugation to an agent, for example)

[0234] L7Cys=Loop 3 Cysteine in second AFFIMER® polypeptide of an in-line fusion polypeptide (i.e., Loop 7 of the in-line fusion). CTCys=C-terminal Cysteine (for conjugation to an agent, for example); additional C at C-terminus NTCys=N-terminal Cysteine (for conjugation to an agent, for example); replace N-terminus G5 with C LNCys=Linker Cysteine (for conjugation to an agent, for example); replace central A of linker with C

[0235]

[0223] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to any one of SEQ ID NOs: 213-316. In some embodiments, a polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 213-316.

[0236]

[0224] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 213. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 213. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 213. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 213. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 213. In some embodiments, a polypeptide comprises SEQ ID NO: 213. In some embodiments, the polypeptide consists of SEQ ID NO: 213.

[0237]

[0225] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 214. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 214. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 214. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 214. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 214. In some embodiments, a polypeptide comprises SEQ ID NO: 214. In some embodiments, the polypeptide consists of SEQ ID NO: 214.

[0238]

[0226] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 215. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 215. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 215. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 215. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 215. In some embodiments, a polypeptide comprises SEQ ID NO: 215. In some embodiments, the polypeptide consists of SEQ ID NO: 215.

[0239]

[0227] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 216. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 216. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 216. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 216. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 216. In some embodiments, a polypeptide comprises SEQ ID NO: 216. In some embodiments, the polypeptide consists of SEQ ID NO: 216.

[0240]

[0228] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 217. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 217. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 217. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 217. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 217. In some embodiments, a polypeptide comprises SEQ ID NO: 217. In some embodiments, the polypeptide consists of SEQ ID NO: 217.

[0241]

[0229] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 218. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 218. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 218. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 218. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 218. In some embodiments, a polypeptide comprises SEQ ID NO: 218. In some embodiments, the polypeptide consists of SEQ ID NO: 218.

[0242]

[0230] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 219. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 219. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 219. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 219. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 219. In some embodiments, a polypeptide comprises SEQ ID NO: 219. In some embodiments, the polypeptide consists of SEQ ID NO: 219.

[0243]

[0231] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 220. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 220. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 220. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 220. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 220. In some embodiments, a polypeptide comprises SEQ ID NO: 220. In some embodiments, the polypeptide consists of SEQ ID NO: 220.

[0244]

[0232] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 221. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 221. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 221. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 221. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 221. In some embodiments, a polypeptide comprises SEQ ID NO: 221. In some embodiments, the polypeptide consists of SEQ ID NO: 221.

[0245]

[0233] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 222. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 222. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 222. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 222. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 222. In some embodiments, a polypeptide comprises SEQ ID NO: 222. In some embodiments, the polypeptide consists of SEQ ID NO: 222.

[0246]

[0234] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 223. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 223. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 223. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 223. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 223. In some embodiments, a polypeptide comprises SEQ ID NO: 223. In some embodiments, the polypeptide consists of SEQ ID NO: 223.

[0247]

[0235] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 224. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 224. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 224. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 224. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 224. In some embodiments, a polypeptide comprises SEQ ID NO: 224. In some embodiments, the polypeptide consists of SEQ ID NO: 224.

[0248]

[0236] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 225. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 225. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 225. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 225. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 225. In some embodiments, a polypeptide comprises SEQ ID NO: 225. In some embodiments, the polypeptide consists of SEQ ID NO: 225.

[0249]

[0237] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 226. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 226. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 226. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 226. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 226. In some embodiments, a polypeptide comprises SEQ ID NO: 226. In some embodiments, the polypeptide consists of SEQ ID NO: 226.

[0250]

[0238] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 227. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 227. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 227. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 227. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 227. In some embodiments, a polypeptide comprises SEQ ID NO: 227. In some embodiments, the polypeptide consists of SEQ ID NO: 227.

[0251]

[0239] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 228. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 228. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 228. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 228. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 228. In some embodiments, a polypeptide comprises SEQ ID NO: 228. In some embodiments, the polypeptide consists of SEQ ID NO: 228.

[0252]

[0240] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 229. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 229. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 229. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 229. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 229. In some embodiments, a polypeptide comprises SEQ ID NO: 229. In some embodiments, the polypeptide consists of SEQ ID NO: 229.

[0253]

[0241] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 230. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 230. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 230. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 230. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 230. In some embodiments, a polypeptide comprises SEQ ID NO: 230. In some embodiments, the polypeptide consists of SEQ ID NO: 230.

[0242] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 231. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 231. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 231. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 231. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 231. In some embodiments, a polypeptide comprises SEQ ID NO: 231. In some embodiments, the polypeptide consists of SEQ ID NO: 231.

[0254]

[0243] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 232. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 232. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 232. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 232. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 232. In some embodiments, a polypeptide comprises SEQ ID NO: 232. In some embodiments, the polypeptide consists of SEQ ID NO: 232.

[0255]

[0244] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 233. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 233. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 233. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 233. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 233. In some embodiments, a polypeptide comprises SEQ ID NO: 233. In some embodiments, the polypeptide consists of SEQ ID NO: 233.

[0256]

[0245] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 234. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 234. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 234. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 234. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 234. In some embodiments, a polypeptide comprises SEQ ID NO: 234. In some embodiments, the polypeptide consists of SEQ ID NO: 234.

[0257]

[0246] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 235. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 235. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 235. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 235. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 235. In some embodiments, a polypeptide comprises SEQ ID NO: 235. In some embodiments, the polypeptide consists of SEQ ID NO: 235.

[0258]

[0247] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 236. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 236. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 236. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 236. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 236. In some embodiments, a polypeptide comprises SEQ ID NO: 236. In some embodiments, the polypeptide consists of SEQ ID NO: 236.

[0259]

[0248] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 237. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 237. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 237. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 237. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 237. In some embodiments, a polypeptide comprises SEQ ID NO: 237. In some embodiments, the polypeptide consists of SEQ ID NO: 237.

[0260]

[0249] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 238. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 238. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 238. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 238. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 238. In some embodiments, a polypeptide comprises SEQ ID NO: 238. In some embodiments, the polypeptide consists of SEQ ID NO: 238.

[0261]

[0250] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 239. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 239. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 239. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 239. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 239. In some embodiments, a polypeptide comprises SEQ ID NO: 239. In some embodiments, the polypeptide consists of SEQ ID NO: 239.

[0262]

[0251] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 240. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 240. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 240. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 240. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 240. In some embodiments, a polypeptide comprises SEQ ID NO: 240. In some embodiments, the polypeptide consists of SEQ ID NO: 240.

[0263]

[0252] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 241. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 241. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 241. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 241. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 241. In some embodiments, a polypeptide comprises SEQ ID NO: 241. In some embodiments, the polypeptide consists of SEQ ID NO: 241.

[0264]

[0253] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 242. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 242. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 242. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 242. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 242. In some embodiments, a polypeptide comprises SEQ ID NO: 242. In some embodiments, the polypeptide consists of SEQ ID NO: 242.

[0265]

[0254] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 243. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 243. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 243. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 243. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 243. In some embodiments, a polypeptide comprises SEQ ID NO: 243. In some embodiments, the polypeptide consists of SEQ ID NO: 243.

[0266]

[0255] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 244. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 244. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 244. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 244. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 244. In some embodiments, a polypeptide comprises SEQ ID NO: 244. In some embodiments, the polypeptide consists of SEQ ID NO: 244.

[0267]

[0256] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 245. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 245. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 245. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 245. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 245. In some embodiments, a polypeptide comprises SEQ ID NO: 245. In some embodiments, the polypeptide consists of SEQ ID NO: 245.

[0268]

[0257] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 246. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 246. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 246. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 246. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 246. In some embodiments, a polypeptide comprises SEQ ID NO: 246. In some embodiments, the polypeptide consists of SEQ ID NO: 246.

[0269]

[0258] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 247. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 247. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 247. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 247. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 247. In some embodiments, a polypeptide comprises SEQ ID NO: 247. In some embodiments, the polypeptide consists of SEQ ID NO: 247.

[0270]

[0259] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 248. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 248. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 248. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 248. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 248. In some embodiments, a polypeptide comprises SEQ ID NO: 248. In some embodiments, the polypeptide consists of SEQ ID NO: 248.

[0271]

[0260] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 249. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 249. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 249. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 249. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 249. In some embodiments, a polypeptide comprises SEQ ID NO: 249. In some embodiments, the polypeptide consists of SEQ ID NO: 249.

[0261] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 250. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 250. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 250. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 250. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 250. In some embodiments, a polypeptide comprises SEQ ID NO: 250. In some embodiments, the polypeptide consists of SEQ ID NO: 250.

[0272]

[0262] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 251. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 251. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 251. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 251. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 251. In some embodiments, a polypeptide comprises SEQ ID NO: 251. In some embodiments, the polypeptide consists of SEQ ID NO: 251.

[0273]

[0263] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 252. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 252. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 252. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 252. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 252. In some embodiments, a polypeptide comprises SEQ ID NO: 252. In some embodiments, the polypeptide consists of SEQ ID NO: 252.

[0274]

[0264] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 253. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 253. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 253. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 253. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 253. In some embodiments, a polypeptide comprises SEQ ID NO: 253. In some embodiments, the polypeptide consists of SEQ ID NO: 253.

[0275]

[0265] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 254. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 254. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 254. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 254. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 254. In some embodiments, a polypeptide comprises SEQ ID NO: 254. In some embodiments, the polypeptide consists of SEQ ID NO: 254.

[0276]

[0266] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 255. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 255. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 255. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 255. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 255. In some embodiments, a polypeptide comprises SEQ ID NO: 255. In some embodiments, the polypeptide consists of SEQ ID NO: 255.

[0277]

[0267] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 256. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 256. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 256. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 256. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 256. In some embodiments, a polypeptide comprises SEQ ID NO: 256. In some embodiments, the polypeptide consists of SEQ ID NO: 256.

[0278]

[0268] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 257. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 257. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 257. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 257. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 257. In some embodiments, a polypeptide comprises SEQ ID NO: 257. In some embodiments, the polypeptide consists of SEQ ID NO: 257.

[0279]

[0269] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 258. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 258. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 258. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 258. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 258. In some embodiments, a polypeptide comprises SEQ ID NO: 258. In some embodiments, the polypeptide consists of SEQ ID NO: 258.

[0280]

[0270] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 259. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 259. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 259. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 259. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 259. In some embodiments, a polypeptide comprises SEQ ID NO: 259. In some embodiments, the polypeptide consists of SEQ ID NO: 259.

[0281]

[0271] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 260. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 260. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 260. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 260. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 260. In some embodiments, a polypeptide comprises SEQ ID NO: 260. In some embodiments, the polypeptide consists of SEQ ID NO: 260.

[0282]

[0272] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 261. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 261. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 261. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 261. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 261. In some embodiments, a polypeptide comprises SEQ ID NO: 261. In some embodiments, the polypeptide consists of SEQ ID NO: 261.

[0283]

[0273] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 262. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 262. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 262. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 262. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 262. In some embodiments, a polypeptide comprises SEQ ID NO: 262. In some embodiments, the polypeptide consists of SEQ ID NO: 262.

[0284]

[0274] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 263. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 263. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 263. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 263. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 263. In some embodiments, a polypeptide comprises SEQ ID NO: 263. In some embodiments, the polypeptide consists of SEQ ID NO: 263.

[0285]

[0275] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 264. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 264. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 264. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 264. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 264. In some embodiments, a polypeptide comprises SEQ ID NO: 264. In some embodiments, the polypeptide consists of SEQ ID NO: 264.

[0286]

[0276] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 265. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 265. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 265. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 265. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 265. In some embodiments, a polypeptide comprises SEQ ID NO: 265. In some embodiments, the polypeptide consists of SEQ ID NO: 265.

[0287]

[0277] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 266. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 266. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 266. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 266. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 266. In some embodiments, a polypeptide comprises SEQ ID NO: 266. In some embodiments, the polypeptide consists of SEQ ID NO: 266.

[0288]

[0278] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 267. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 267. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 267. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 267. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 267. In some embodiments, a polypeptide comprises SEQ ID NO: 267. In some embodiments, the polypeptide consists of SEQ ID NO: 267.

[0289]

[0279] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 268. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 268. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 268. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 268. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 268. In some embodiments, a polypeptide comprises SEQ ID NO: 268. In some embodiments, the polypeptide consists of SEQ ID NO: 268.

[0280] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 269. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 269. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 269. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 269. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 269. In some embodiments, a polypeptide comprises SEQ ID NO: 269. In some embodiments, the polypeptide consists of SEQ ID NO: 269.

[0290]

[0281] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 270. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 270. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 270. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 270. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 270. In some embodiments, a polypeptide comprises SEQ ID NO: 270. In some embodiments, the polypeptide consists of SEQ ID NO: 270.

[0291]

[0282] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 271. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 271. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 271. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 271. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 271. In some embodiments, a polypeptide comprises SEQ ID NO: 271. In some embodiments, the polypeptide consists of SEQ ID NO: 271.

[0292]

[0283] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 272. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 272. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 272. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 272. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 272. In some embodiments, a polypeptide comprises SEQ ID NO: 272. In some embodiments, the polypeptide consists of SEQ ID NO: 272.

[0293]

[0284] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 273. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 273. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 273. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 273. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 273. In some embodiments, a polypeptide comprises SEQ ID NO: 273. In some embodiments, the polypeptide consists of SEQ ID NO: 273.

[0294]

[0285] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 274. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 274. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 274. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 274. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 274. In some embodiments, a polypeptide comprises SEQ ID NO: 274. In some embodiments, the polypeptide consists of SEQ ID NO: 274.

[0295]

[0286] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 275. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 275. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 275. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 275. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 275. In some embodiments, a polypeptide comprises SEQ ID NO: 275. In some embodiments, the polypeptide consists of SEQ ID NO: 275.

[0296]

[0287] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 276. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 276. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 276. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 276. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 276. In some embodiments, a polypeptide comprises SEQ ID NO: 276. In some embodiments, the polypeptide consists of SEQ ID NO: 276.

[0297]

[0288] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 277. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 277. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 277. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 277. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 277. In some embodiments, a polypeptide comprises SEQ ID NO: 277. In some embodiments, the polypeptide consists of SEQ ID NO: 277.

[0298]

[0289] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 278. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 278. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 278. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 278. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 278. In some embodiments, a polypeptide comprises SEQ ID NO: 278. In some embodiments, the polypeptide consists of SEQ ID NO: 278.

[0299]

[0290] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 279. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 279. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 279. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 279. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 279. In some embodiments, a polypeptide comprises SEQ ID NO: 279. In some embodiments, the polypeptide consists of SEQ ID NO: 279.

[0300]

[0291] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 280. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 280. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 280. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 280. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 280. In some embodiments, a polypeptide comprises SEQ ID NO: 280. In some embodiments, the polypeptide consists of SEQ ID NO: 280.

[0301]

[0292] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 281. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 281. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 281. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 281. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 281. In some embodiments, a polypeptide comprises SEQ ID NO: 281. In some embodiments, the polypeptide consists of SEQ ID NO: 281.

[0302]

[0293] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 282. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 282. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 282. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 282. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 282. In some embodiments, a polypeptide comprises SEQ ID NO: 282. In some embodiments, the polypeptide consists of SEQ ID NO: 282.

[0303]

[0294] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 283. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 283. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 283. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 283. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 283. In some embodiments, a polypeptide comprises SEQ ID NO: 283. In some embodiments, the polypeptide consists of SEQ ID NO: 283.

[0304]

[0295] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 284. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 284. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 284. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 284. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 284. In some embodiments, a polypeptide comprises SEQ ID NO: 284. In some embodiments, the polypeptide consists of SEQ ID NO: 284.

[0305]

[0296] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 285. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 285. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 285. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 285. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 285. In some embodiments, a polypeptide comprises SEQ ID NO: 285. In some embodiments, the polypeptide consists of SEQ ID NO: 285.

[0306]

[0297] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 286. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 286. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 286. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 286. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 286. In some embodiments, a polypeptide comprises SEQ ID NO: 286. In some embodiments, the polypeptide consists of SEQ ID NO: 286.

[0307]

[0298] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 287. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 287. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 287. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 287. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 287. In some embodiments, a polypeptide comprises SEQ ID NO: 287. In some embodiments, the polypeptide consists of SEQ ID NO: 287.

[0299] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 288. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 288. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 288. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 288. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 288. In some embodiments, a polypeptide comprises SEQ ID NO: 288. In some embodiments, the polypeptide consists of SEQ ID NO: 288.

[0308]

[0300] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 289. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 289. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 289. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 289. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 289. In some embodiments, a polypeptide comprises SEQ ID NO: 289. In some embodiments, the polypeptide consists of SEQ ID NO: 289.

[0309]

[0301] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 290. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 290. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 290. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 290. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 290. In some embodiments, a polypeptide comprises SEQ ID NO: 290. In some embodiments, the polypeptide consists of SEQ ID NO: 290.

[0310]

[0302] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 291. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 291. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 291. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 291. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 291. In some embodiments, a polypeptide comprises SEQ ID NO: 291. In some embodiments, the polypeptide consists of SEQ ID NO: 291.

[0311]

[0303] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 292. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 292. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 292. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 292. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 292. In some embodiments, a polypeptide comprises SEQ ID NO: 292. In some embodiments, the polypeptide consists of SEQ ID NO: 292.

[0312]

[0304] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 293. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 293. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 293. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 293. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 293. In some embodiments, a polypeptide comprises SEQ ID NO: 293. In some embodiments, the polypeptide consists of SEQ ID NO: 293.

[0313]

[0305] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 294. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 294. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 294. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 294. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 294. In some embodiments, a polypeptide comprises SEQ ID NO: 294. In some embodiments, the polypeptide consists of SEQ ID NO: 294.

[0314]

[0306] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 295. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 295. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 295. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 295. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 295. In some embodiments, a polypeptide comprises SEQ ID NO: 295. In some embodiments, the polypeptide consists of SEQ ID NO: 295.

[0315]

[0307] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 296. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 296. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 296. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 296. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 296. In some embodiments, a polypeptide comprises SEQ ID NO: 296. In some embodiments, the polypeptide consists of SEQ ID NO: 296.

[0316]

[0308] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 297. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 297. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 297. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 297. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 297. In some embodiments, a polypeptide comprises SEQ ID NO: 297. In some embodiments, the polypeptide consists of SEQ ID NO: 297.

[0317]

[0309] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 298. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 298. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 298. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 298. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 298. In some embodiments, a polypeptide comprises SEQ ID NO: 298. In some embodiments, the polypeptide consists of SEQ ID NO: 298.

[0318]

[0310] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 299. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 299. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 299. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 299. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 299. In some embodiments, a polypeptide comprises SEQ ID NO: 299. In some embodiments, the polypeptide consists of SEQ ID NO: 299.

[0319]

[0311] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 300. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 300. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 300. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 300. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 300. In some embodiments, a polypeptide comprises SEQ ID NO: 300. In some embodiments, the polypeptide consists of SEQ ID NO: 300.

[0320]

[0312] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 301. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 301. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 301. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 301. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 301. In some embodiments, a polypeptide comprises SEQ ID NO: 301. In some embodiments, the polypeptide consists of SEQ ID NO: 301.

[0321]

[0313] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 302. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 302. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 302. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 302. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 302. In some embodiments, a polypeptide comprises SEQ ID NO: 302. In some embodiments, the polypeptide consists of SEQ ID NO: 302.

[0322]

[0314] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 303. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 303. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 303. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 303. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 303. In some embodiments, a polypeptide comprises SEQ ID NO: 303. In some embodiments, the polypeptide consists of SEQ ID NO: 303.

[0323]

[0315] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 304. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 304. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 304. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 304. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 304. In some embodiments, a polypeptide comprises SEQ ID NO: 304. In some embodiments, the polypeptide consists of SEQ ID NO: 304.

[0324]

[0316] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 305. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 305. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 305. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 305. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 305. In some embodiments, a polypeptide comprises SEQ ID NO: 305. In some embodiments, the polypeptide consists of SEQ ID NO: 305.

[0325]

[0317] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 306. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 306. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 306. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 306. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 306. In some embodiments, a polypeptide comprises SEQ ID NO: 306. In some embodiments, the polypeptide consists of SEQ ID NO: 306.

[0318] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 307. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 307. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 307. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 307. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 307. In some embodiments, a polypeptide comprises SEQ ID NO: 307. In some embodiments, the polypeptide consists of SEQ ID NO: 307.

[0326]

[0319] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 308. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 308. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 308. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 308. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 308. In some embodiments, a polypeptide comprises SEQ ID NO: 308. In some embodiments, the polypeptide consists of SEQ ID NO: 308.

[0327]

[0320] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 309. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 309. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 309. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 309. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 309. In some embodiments, a polypeptide comprises SEQ ID NO: 309. In some embodiments, the polypeptide consists of SEQ ID NO: 309.

[0328]

[0321] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 310. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 310. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 310. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 310. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 310. In some embodiments, a polypeptide comprises SEQ ID NO: 310. In some embodiments, the polypeptide consists of SEQ ID NO: 310.

[0329]

[0322] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 311. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 311. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 311. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 311. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 311. In some embodiments, a polypeptide comprises SEQ ID NO: 311. In some embodiments, the polypeptide consists of SEQ ID NO: 311.

[0330]

[0323] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 312. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 312. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 312. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 312. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 312. In some embodiments, a polypeptide comprises SEQ ID NO: 312. In some embodiments, the polypeptide consists of SEQ ID NO: 312.

[0331]

[0324] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 313. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 313. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 313. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 313. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 313. In some embodiments, a polypeptide comprises SEQ ID NO: 313. In some embodiments, the polypeptide consists of SEQ ID NO: 313.

[0332]

[0325] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 314. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 314. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 314. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 314. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 314. In some embodiments, a polypeptide comprises SEQ ID NO: 314. In some embodiments, the polypeptide consists of SEQ ID NO: 314.

[0333]

[0326] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 315. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 315. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 315. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 315. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 315. In some embodiments, a polypeptide comprises SEQ ID NO: 315. In some embodiments, the polypeptide consists of SEQ ID NO: 315.

[0334]

[0327] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 316. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 316. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 316. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 316. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 316. In some embodiments, a polypeptide comprises SEQ ID NO: 316. In some embodiments, the polypeptide consists of SEQ ID NO: 316.

[0335] Fusion Proteins and Protein Conjugates

[0336]

[0328] The polypeptides provided herein, in some aspects, are components of a fusion protein. A fusion protein includes a single polypeptide chain created by joining the genes encoding two or more proteins or peptides. The resulting polypeptide chain is expressed as a single, continuous protein. Fusion proteins are typically produced using recombinant DNA technology. The genes encoding the desired proteins are fused together in a specific order, and the combined gene is then inserted into an expression vector, for example. The host cells (such as bacteria, yeast, or mammalian cells) express the fusion protein as a single polypeptide chain. Fusion proteins typically have a continuous amino acid sequence, with each protein domain or peptide segment directly connected to the next.

[0337]

[0329] Thus, the present disclosure provides, in some embodiments, fusion proteins comprising (a) a polypeptide comprising (i) a scaffold comprising a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1, wherein the scaffold sequence includes an insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 and a mutation at an amino acid position corresponding to N32 of the amino acid sequence of SEQ ID NO: 1, and (ii) a heterologous peptide, and (b) at least one additional polypeptide.

[0338]

[0330] The polypeptides provided herein, in some aspects, are components of a conjugate. A protein conjugate can be created by chemically linking a protein to another molecule, which could be another protein, peptide, drug, or other functional group. The linkage is typically covalent and involves chemical bonds other than peptide bonds. Protein conjugates can be produced through chemical conjugation methods, where the protein and the conjugate molecule (e.g., a drug or another protein) are linked using specific chemical reagents. This process can occur after the individual components have been separately synthesized or purified. Protein conjugates typically include distinct molecules that are covalently attached to each other through chemical bonds. The linked components retain their individual structures but are chemically connected.

[0339]

[0331] Thus, the present disclosure provides, in some embodiments, fusion proteins comprising (a) a polypeptide comprising (i) a scaffold comprising a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1, wherein the scaffold sequence includes an insertion of an amino acid between amino acid positions corresponding to Ml and 12 of the amino acid sequence of SEQ ID NO: 1 and a mutation at an amino acid position corresponding to N32 of the amino acid sequence of SEQ ID NO: 1, and (ii) a heterologous peptide, and (b) a molecule (e.g., moiety) of interest.

[0340]

[0332] In some embodiments, the molecule of interest is a second AFFIMER® polypeptide. In some embodiments, the fusion protein is a homodimer; i.e., the second AFFIMER® polypeptide is identical to a first AFFIMER® polypeptide. In some embodiments, the fusion protein is a heterodimer; i.e., the second AFFIMER® polypeptide is different from a first AFFIMER® polypeptide. Exemplary homodimer and heterodimer sequences are provided in Tables 2-12.

[0341]

[0333] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 317. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 317. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 317. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 317. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 317. In some embodiments, a polypeptide comprises SEQ ID NO: 317. In some embodiments, the polypeptide consists of SEQ ID NO: 317.

[0342]

[0334] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 318. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 318. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 318. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 318. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 318. In some embodiments, a polypeptide comprises SEQ ID NO: 318. In some embodiments, the polypeptide consists of SEQ ID NO: 318.

[0343]

[0335] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 319. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 319. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 319. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 319. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 319. In some embodiments, a polypeptide comprises SEQ ID NO: 319. In some embodiments, the polypeptide consists of SEQ ID NO: 319.

[0344]

[0336] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 320. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 320. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 320. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 320. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 320. In some embodiments, a polypeptide comprises SEQ ID NO: 320. In some embodiments, the polypeptide consists of SEQ ID NO: 320.

[0345]

[0337] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 321. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 321. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 321. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 321. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 321. In some embodiments, a polypeptide comprises SEQ ID NO: 321. In some embodiments, the polypeptide consists of SEQ ID NO: 321.

[0346]

[0338] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 322. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 322. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 322. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 322. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 322. In some embodiments, a polypeptide comprises SEQ ID NO: 322. In some embodiments, the polypeptide consists of SEQ ID NO: 322.

[0347]

[0339] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 323. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 323. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 323. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 323. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 323. In some embodiments, a polypeptide comprises SEQ ID NO: 323. In some embodiments, the polypeptide consists of SEQ ID NO: 323.

[0348]

[0340] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 324. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 324. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 324. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 324. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 324. In some embodiments, a polypeptide comprises SEQ ID NO: 324. In some embodiments, the polypeptide consists of SEQ ID NO: 324.

[0349]

[0341] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 325. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 325. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 325. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 325. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 325. In some embodiments, a polypeptide comprises SEQ ID NO: 325. In some embodiments, the polypeptide consists of SEQ ID NO: 325.

[0350]

[0342] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 326. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 326. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 326. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 326. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 326. In some embodiments, a polypeptide comprises SEQ ID NO: 326. In some embodiments, the polypeptide consists of SEQ ID NO: 326.

[0351]

[0343] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 327. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 327. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 327. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 327. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 327. In some embodiments, a polypeptide comprises SEQ ID NO: 327. In some embodiments, the polypeptide consists of SEQ ID NO: 327.

[0352]

[0344] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 328. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 328. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 328. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 328. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 328. In some embodiments, a polypeptide comprises SEQ ID NO: 328. In some embodiments, the polypeptide consists of SEQ ID NO: 328.

[0353]

[0345] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 329. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 329. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 329. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 329. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 329. In some embodiments, a polypeptide comprises SEQ ID NO: 329. In some embodiments, the polypeptide consists of SEQ ID NO: 329.

[0354]

[0346] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 330. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 330. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 330. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 330. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 330. In some embodiments, a polypeptide comprises SEQ ID NO: 330. In some embodiments, the polypeptide consists of SEQ ID NO: 330.

[0347] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 331. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 331. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 331. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 331. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 331. In some embodiments, a polypeptide comprises SEQ ID NO: 331. In some embodiments, the polypeptide consists of SEQ ID NO: 331.

[0355]

[0348] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 332. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 332. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 332. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 332. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 332. In some embodiments, a polypeptide comprises SEQ ID NO: 332. In some embodiments, the polypeptide consists of SEQ ID NO: 332.

[0356]

[0349] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 333. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 333. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 333. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 333. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 333. In some embodiments, a polypeptide comprises SEQ ID NO: 333. In some embodiments, the polypeptide consists of SEQ ID NO: 333.

[0357]

[0350] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 334. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 334. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 334. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 334. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 334. In some embodiments, a polypeptide comprises SEQ ID NO: 334. In some embodiments, the polypeptide consists of SEQ ID NO: 334.

[0358]

[0351] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 335. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 335. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 335. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 335. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 335. In some embodiments, a polypeptide comprises SEQ ID NO: 335. In some embodiments, the polypeptide consists of SEQ ID NO: 335.

[0359]

[0352] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 336. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 336. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 336. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 336. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 336. In some embodiments, a polypeptide comprises SEQ ID NO: 336. In some embodiments, the polypeptide consists of SEQ ID NO: 336.

[0360]

[0353] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 337. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 337. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 337. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 337. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 337. In some embodiments, a polypeptide comprises SEQ ID NO: 337. In some embodiments, the polypeptide consists of SEQ ID NO: 337.

[0361]

[0354] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 338. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 338. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 338. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 338. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 338. In some embodiments, a polypeptide comprises SEQ ID NO: 338. In some embodiments, the polypeptide consists of SEQ ID NO: 338.

[0362]

[0355] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 339. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 339. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 339. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 339. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 339. In some embodiments, a polypeptide comprises SEQ ID NO: 339. In some embodiments, the polypeptide consists of SEQ ID NO: 339.

[0363]

[0356] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 340. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 340. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 340. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 340. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 340. In some embodiments, a polypeptide comprises SEQ ID NO: 340. In some embodiments, the polypeptide consists of SEQ ID NO: 340.

[0364]

[0357] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 341. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 341. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 341. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 341. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 341. In some embodiments, a polypeptide comprises SEQ ID NO: 341. In some embodiments, the polypeptide consists of SEQ ID NO: 341.

[0365]

[0358] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 342. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 342. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 342. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 342. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 342. In some embodiments, a polypeptide comprises SEQ ID NO: 342. In some embodiments, the polypeptide consists of SEQ ID NO: 342.

[0366]

[0359] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 343. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 343. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 343. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 343. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 343. In some embodiments, a polypeptide comprises SEQ ID NO: 343. In some embodiments, the polypeptide consists of SEQ ID NO: 343.

[0367]

[0360] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 344. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 344. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 344. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 344. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 344. In some embodiments, a polypeptide comprises SEQ ID NO: 344. In some embodiments, the polypeptide consists of SEQ ID NO: 344.

[0368]

[0361] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 345. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 345. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 345. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 345. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 345. In some embodiments, a polypeptide comprises SEQ ID NO: 345. In some embodiments, the polypeptide consists of SEQ ID NO: 345.

[0369]

[0362] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 346. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 346. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 346. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 346. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 346. In some embodiments, a polypeptide comprises SEQ ID NO: 346. In some embodiments, the polypeptide consists of SEQ ID NO: 346.

[0370]

[0363] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 347. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 347. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 347. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 347. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 347. In some embodiments, a polypeptide comprises SEQ ID NO: 347. In some embodiments, the polypeptide consists of SEQ ID NO: 347.

[0371]

[0364] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 348. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 348. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 348. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 348. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 348. In some embodiments, a polypeptide comprises SEQ ID NO: 348. In some embodiments, the polypeptide consists of SEQ ID NO: 348.

[0372]

[0365] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 349. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 349. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 349. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 349. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 349. In some embodiments, a polypeptide comprises SEQ ID NO: 349. In some embodiments, the polypeptide consists of SEQ ID NO: 349.

[0366] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 350. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 350. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 350. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 350. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 350. In some embodiments, a polypeptide comprises SEQ ID NO: 350. In some embodiments, the polypeptide consists of SEQ ID NO: 350.

[0373]

[0367] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 351. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 351. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 351. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 351. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 351. In some embodiments, a polypeptide comprises SEQ ID NO: 351. In some embodiments, the polypeptide consists of SEQ ID NO: 351.

[0374]

[0368] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 352. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 352. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 352. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 352. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 352. In some embodiments, a polypeptide comprises SEQ ID NO: 352. In some embodiments, the polypeptide consists of SEQ ID NO: 352.

[0375]

[0369] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 353. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 353. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 353. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 353. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 353. In some embodiments, a polypeptide comprises SEQ ID NO: 353. In some embodiments, the polypeptide consists of SEQ ID NO: 353.

[0376]

[0370] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 354. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 354. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 354. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 354. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 354. In some embodiments, a polypeptide comprises SEQ ID NO: 354. In some embodiments, the polypeptide consists of SEQ ID NO: 354.

[0377]

[0371] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 355. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 355. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 355. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 355. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 355. In some embodiments, a polypeptide comprises SEQ ID NO: 355. In some embodiments, the polypeptide consists of SEQ ID NO: 355.

[0378]

[0372] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 356. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 356. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 356. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 356. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 356. In some embodiments, a polypeptide comprises SEQ ID NO: 356. In some embodiments, the polypeptide consists of SEQ ID NO: 356.

[0379]

[0373] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 357. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 357. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 357. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 357. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 357. In some embodiments, a polypeptide comprises SEQ ID NO: 357. In some embodiments, the polypeptide consists of SEQ ID NO: 357.

[0380]

[0374] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 358. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 358. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 358. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 358. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 358. In some embodiments, a polypeptide comprises SEQ ID NO: 358. In some embodiments, the polypeptide consists of SEQ ID NO: 358.

[0381]

[0375] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 359. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 359. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 359. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 359. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 359. In some embodiments, a polypeptide comprises SEQ ID NO: 359. In some embodiments, the polypeptide consists of SEQ ID NO: 359.

[0382]

[0376] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 360. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 360. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 360. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 360. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 360. In some embodiments, a polypeptide comprises SEQ ID NO: 360. In some embodiments, the polypeptide consists of SEQ ID NO: 360.

[0383]

[0377] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 361. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 361. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 361. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 361. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 361. In some embodiments, a polypeptide comprises SEQ ID NO: 361. In some embodiments, the polypeptide consists of SEQ ID NO: 361.

[0384]

[0378] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 362. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 362. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 362. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 362. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 362. In some embodiments, a polypeptide comprises SEQ ID NO: 362. In some embodiments, the polypeptide consists of SEQ ID NO: 362.

[0385]

[0379] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 363. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 363. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 363. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 363. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 363. In some embodiments, a polypeptide comprises SEQ ID NO: 363. In some embodiments, the polypeptide consists of SEQ ID NO: 363.

[0386]

[0380] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 364. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 364. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 364. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 364. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 364. In some embodiments, a polypeptide comprises SEQ ID NO: 364. In some embodiments, the polypeptide consists of SEQ ID NO: 364.

[0387]

[0381] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 365. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 365. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 365. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 365. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 365. In some embodiments, a polypeptide comprises SEQ ID NO: 365. In some embodiments, the polypeptide consists of SEQ ID NO: 365.

[0388]

[0382] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 366. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 366. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 366. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 366. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 366. In some embodiments, a polypeptide comprises SEQ ID NO: 366. In some embodiments, the polypeptide consists of SEQ ID NO: 366.

[0389]

[0383] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 367. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 367. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 367. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 367. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 367. In some embodiments, a polypeptide comprises SEQ ID NO: 367. In some embodiments, the polypeptide consists of SEQ ID NO: 367.

[0390]

[0384] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 368. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 368. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 368. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 368. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 368. In some embodiments, a polypeptide comprises SEQ ID NO: 368. In some embodiments, the polypeptide consists of SEQ ID NO: 368.

[0385] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 369. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 369. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 369. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 369. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 369. In some embodiments, a polypeptide comprises SEQ ID NO: 369. In some embodiments, the polypeptide consists of SEQ ID NO: 369.

[0391]

[0386] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 370. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 370. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 370. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 370. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 370. In some embodiments, a polypeptide comprises SEQ ID NO: 370. In some embodiments, the polypeptide consists of SEQ ID NO: 370.

[0392]

[0387] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 371. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 371. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 371. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 371. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 371. In some embodiments, a polypeptide comprises SEQ ID NO: 371. In some embodiments, the polypeptide consists of SEQ ID NO: 371.

[0393]

[0388] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 372. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 372. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 372. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 372. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 372. In some embodiments, a polypeptide comprises SEQ ID NO: 372. In some embodiments, the polypeptide consists of SEQ ID NO: 372.

[0394]

[0389] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 373. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 373. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 373. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 373. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 373. In some embodiments, a polypeptide comprises SEQ ID NO: 373. In some embodiments, the polypeptide consists of SEQ ID NO: 373.

[0395]

[0390] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 374. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 374. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 374. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 374. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 374. In some embodiments, a polypeptide comprises SEQ ID NO: 374. In some embodiments, the polypeptide consists of SEQ ID NO: 374.

[0396]

[0391] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 375. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 375. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 375. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 375. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 375. In some embodiments, a polypeptide comprises SEQ ID NO: 375. In some embodiments, the polypeptide consists of SEQ ID NO: 375.

[0397]

[0392] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 376. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 376. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 376. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 376. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 376. In some embodiments, a polypeptide comprises SEQ ID NO: 376. In some embodiments, the polypeptide consists of SEQ ID NO: 376.

[0398]

[0393] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 377. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 377. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 377. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 377. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 377. In some embodiments, a polypeptide comprises SEQ ID NO: 377. In some embodiments, the polypeptide consists of SEQ ID NO: 377.

[0399]

[0394] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 378. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 378. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 378. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 378. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 378. In some embodiments, a polypeptide comprises SEQ ID NO: 378. In some embodiments, the polypeptide consists of SEQ ID NO: 378.

[0400]

[0395] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 379. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 379. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 379. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 379. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 379. In some embodiments, a polypeptide comprises SEQ ID NO: 379. In some embodiments, the polypeptide consists of SEQ ID NO: 379.

[0401]

[0396] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 380. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 380. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 380. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 380. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 380. In some embodiments, a polypeptide comprises SEQ ID NO: 380. In some embodiments, the polypeptide consists of SEQ ID NO: 380.

[0402]

[0397] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 381. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 381. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 381. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 381. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 381. In some embodiments, a polypeptide comprises SEQ ID NO: 381. In some embodiments, the polypeptide consists of SEQ ID NO: 381.

[0403]

[0398] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 382. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 382. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 382. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 382. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 382. In some embodiments, a polypeptide comprises SEQ ID NO: 382. In some embodiments, the polypeptide consists of SEQ ID NO: 382.

[0404]

[0399] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 383. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 383. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 383. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 383. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 383. In some embodiments, a polypeptide comprises SEQ ID NO: 383. In some embodiments, the polypeptide consists of SEQ ID NO: 383.

[0405]

[0400] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 384. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 384. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 384. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 384. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 384. In some embodiments, a polypeptide comprises SEQ ID NO: 384. In some embodiments, the polypeptide consists of SEQ ID NO: 384.

[0406]

[0401] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 385. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 385. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 385. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 385. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 385. In some embodiments, a polypeptide comprises SEQ ID NO: 385. In some embodiments, the polypeptide consists of SEQ ID NO: 385.

[0407]

[0402] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 386. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 386. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 386. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 386. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 386. In some embodiments, a polypeptide comprises SEQ ID NO: 386. In some embodiments, the polypeptide consists of SEQ ID NO: 386.

[0408]

[0403] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 387. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 387. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 387. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 387. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 387. In some embodiments, a polypeptide comprises SEQ ID NO: 387. In some embodiments, the polypeptide consists of SEQ ID NO: 387.

[0404] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 388. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 388. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 388. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 388. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 388. In some embodiments, a polypeptide comprises SEQ ID NO: 388. In some embodiments, the polypeptide consists of SEQ ID NO: 388.

[0409] Half-Life Extension

[0410]

[0405] In some embodiments, at least one additional polypeptide of a fusion protein or protein conjugate is a half-life extension molecule (e.g., protein) or modification. Half-life extension proteins, molecules, and modifications include those added to a protein or peptide to extend the half-life of the protein or peptide in the bloodstream. This extension, for example, helps maintain therapeutic levels of a drug for an extended period, reducing the frequency of administration.

[0411]

[0406] Half-life extension molecules increase the half-life of therapeutics to which they are attached through several mechanisms that alter the pharmacokinetics and pharmacodynamics of the drug. By attaching large molecules like polyethylene glycol (PEG) or albumin (e.g., HSA) to the therapeutic, the overall size and molecular weight of the drug increase. This larger size prevents the drug from being rapidly filtered out by the kidneys, thereby reducing renal clearance and extending the drug’s circulation time in the bloodstream. Many half-life extension molecules provide a protective shield around a therapeutic or diagnostic agent, for example. For instance, PEGylation adds a steric barrier that protects the drug from proteolytic enzymes, which can degrade therapeutic proteins and peptides. This protection results in a longer duration of action. Half-life extension molecules can reduce the immunogenicity of the therapeutic agent. By masking epitopes that might be recognized by the immune system, PEG or other protective molecules can decrease the likelihood of an immune response, which can lead to faster clearance of the therapeutic. This helps maintain therapeutic levels in the bloodstream for a longer period. Some half-life extension strategies improve the solubility of hydrophobic drugs, which enhances their stability and distribution in the body. Improved solubility can lead to better pharmacokinetics and extended half-life. Attaching a therapeutic to a naturally long-circulating protein, such as albumin or immunoglobulin (IgG), can also extend its half-life. Albumin, for example, has a long half-life in the bloodstream and by binding to it, the therapeutic inherits this extended circulation time. Modifications that shield the therapeutic from recognition and uptake by the Reduced Clearance by the Reticuloendothelial System (RES), which includes macrophages in the liver and spleen, can significantly extend its half-life. PEGylation and other modifications can help the drug avoid rapid clearance by the RES. Further, polypeptides can be designed to exploit natural recycling pathways. For example, fusion to the Fc region of IgG can exploit the neonatal Fc receptor (FcRn) pathway, which recycles IgG antibodies and extends their half-life. This same mechanism can be used to extend the half-life of Fc-fusion proteins.

[0412]

[0407] Non-limiting examples of half-life extension proteins include Fc regions of antibodies, transferrin, and albumin (e.g., human serum albumin). In some embodiments, the half-life extension protein of a fusion protein or protein conjugate provided herein is an Fc region of an antibody. In some embodiments, the half-life extension protein of a fusion protein or protein conjugate provided herein is transferrin. In some embodiments, the half-life extension protein of a fusion protein or protein conjugate provided herein is albumin (e.g., human serum albumin). In some embodiments, a half-life extension protein or protein conjugate is a protein (e.g., antibody, antibody fragment, or AFFIMER® polypeptide) that binds to a half-life extension protein such as transferrin or albumin, for example.

[0413]

[0408] Non-limiting examples of half-life extension non-protein-based molecules include polyethylene glycol (PEG) molecules, which can protect a polypeptide from degradation and reduce renal clearance. PEGylation increases the molecular size of the therapeutic agent, which reduces its renal clearance. The kidneys filter smaller molecules out of the bloodstream more rapidly, so increasing the size helps the drug stay in circulation longer. PEGylation can also protect the therapeutic agent from degradation by proteolytic enzymes. The PEG chains create a steric barrier that makes it more difficult for proteases to access and degrade the therapeutic protein or peptide. PEGylation can also reduce the immunogenicity of therapeutic proteins and peptides. By shielding the protein with PEG, the immune system is less likely to recognize and mount a response against it, which can also contribute to a longer half-life. PEGylation can also enhance the solubility of hydrophobic drugs, improving their pharmacokinetics and bioavailability. Better solubility often translates to improved circulation time in the body. PEG is involved in the half-life extension of therapeutic agents through a process known as PEGylation. PEGylation refers to the covalent attachment of PEG chains to a therapeutic molecule, such as a protein, peptide, or small molecule drug. Overall, PEGylation prolongs the circulation time of the therapeutic agent in the bloodstream, allowing for less frequent dosing and potentially improved efficacy.

[0414]

[0409] Non-limiting examples of half-life extension modifications include glycosylation. Glycosylation is a biochemical process in which a carbohydrate (glycan) is covalently attached to a protein, lipid, or other organic molecule. N-linked glycosylation refers to the attachment of a glycan to the nitrogen atom (N) of an asparagine (Asn) residue in a protein and usually occurs at Asn-X-Ser / Thr sequences, where X can be any amino acid except proline. O-linked glycosylation refers to the attachment of a glycan to the oxygen atom (O) of serine (Ser) or threonine (Thr) residues in a protein. C-linked glycosylation refers to the attachment of a glycan to the carbon atom (C) of a tryptophan (Trp) residue.

[0415]

[0410] In some embodiments, a fusion protein comprises a serum albumin-binding variant of a human Stefin A protein (see, e.g., International Publication No. W02022 / 023540, the amino acid sequences of which are incorporated herein by reference), also referred to as an HSA-binding AFFIMER® polypeptide.

[0416]

[0411] In some embodiments, a fusion protein comprises a serum albumin-binding variant of a human Stefin A protein comprising a Loop 2 and / or Loop 4 sequence of Table 6. Exemplary variable Loop 2 sequences and variable Loop 4 sequences of polypeptides that bind to HSA are provided in Table 6.

[0417] Exemplary sequences of polypeptides that bind to HSA are provided in Table 7.

[0418] Table 6. Exemplary HSA Binder Loop Sequences

[0419]

[0412] In some embodiments, a heterologous peptide comprises a sequence selected from the amino acid sequence of any one of SEQ ID NOs: 389-492 or 764-767.

[0420]

[0413] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Eoop 2 peptide comprising the amino acid sequence of SEQ ID NO: 389 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 441.

[0421]

[0414] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 390 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 442.

[0422]

[0415] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 391 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 443.

[0423]

[0416] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 392 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 444.

[0424]

[0417] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 393 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 445.

[0425]

[0418] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 394 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 446.

[0426]

[0419] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 395 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 447.

[0427]

[0420] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 396 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 448.

[0428]

[0421] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 397 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 449.

[0422] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 398 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 450.

[0429]

[0423] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 399 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 451.

[0430]

[0424] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 400 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 452.

[0431]

[0425] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 401 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 453.

[0432]

[0426] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 402 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 454.

[0433]

[0427] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 403 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 455.

[0434]

[0428] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 404 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 456.

[0435]

[0429] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 405 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 457.

[0436]

[0430] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 406 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 458.

[0437]

[0431] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 407 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 459.

[0438]

[0432] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 408 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 460.

[0439]

[0433] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 409 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 461.

[0434] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 410 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 462.

[0440]

[0435] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 411 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 463.

[0441]

[0436] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 412 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 464.

[0442]

[0437] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 413 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 465.

[0443]

[0438] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 414 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 466.

[0444]

[0439] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 415 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 467.

[0445]

[0440] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 416 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 468.

[0446]

[0441] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 417 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 469.

[0447]

[0442] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 418 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 470.

[0448]

[0443] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 419 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 471.

[0449]

[0444] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 420 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 472.

[0450]

[0445] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 421 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 473.

[0446] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 422 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 474.

[0451]

[0447] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 423 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 475.

[0452]

[0448] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 424 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 476.

[0453]

[0449] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 425 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 477.

[0454]

[0450] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 426 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 478.

[0455]

[0451] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 427 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 479.

[0456]

[0452] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 428 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 480.

[0457]

[0453] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 429 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 481.

[0458]

[0454] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 430 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 482.

[0459]

[0455] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 431 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 483.

[0460]

[0456] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 432 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 484.

[0461]

[0457] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 433 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 485.

[0458] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 434 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 486.

[0462]

[0459] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 435 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 487.

[0463]

[0460] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 436 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 488.

[0464]

[0461] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 437 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 489.

[0465]

[0462] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 438 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 490.

[0466]

[0463] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 439 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 491.

[0467]

[0464] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 440 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 492.

[0468]

[0465] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 764 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 766.

[0469]

[0466] In some embodiments, a polypeptide (e.g., an AFFIMER® polypeptide) comprises a variable Loop 2 peptide comprising the amino acid sequence of SEQ ID NO: 765 and a variable Loop 4 peptide comprising the amino acid sequence of SEQ ID NO: 767.

[0470] Table 7. Exemplary HSA Binder Monomer Protein Sequences

[0471] Table 8. Exemplary HSA Binder Dimer Protein Sequences

[0472] Table 9. Exemplary HSA Binder Monomer Protein Sequences with Cysteine Modifications

[0473] Table 10. Exemplary HSA Binder Dimer Protein Sequences with Cysteine Modifications

[0474]

[0467] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to any one of SEQ ID NOs: 493-546. In some embodiments, a polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 493-546.

[0475]

[0468] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 493. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 493. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 493. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 493. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 493. In some embodiments, a polypeptide comprises SEQ ID NO: 493. In some embodiments, the polypeptide consists of SEQ ID NO: 493.

[0476]

[0469] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 494. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 494. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 494. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 494. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 494. In some embodiments, a polypeptide comprises SEQ ID NO: 494. In some embodiments, the polypeptide consists of SEQ ID NO: 494.

[0477]

[0470] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 495. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 495. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 495. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 495. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 495. In some embodiments, a polypeptide comprises SEQ ID NO: 495. In some embodiments, the polypeptide consists of SEQ ID NO: 495.

[0478]

[0471] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 496. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 496. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 496. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 496. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 496. In some embodiments, a polypeptide comprises SEQ ID NO: 496. In some embodiments, the polypeptide consists of SEQ ID NO: 496.

[0479]

[0472] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 497. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 497. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 497. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 497. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 497. In some embodiments, a polypeptide comprises SEQ ID NO: 497. In some embodiments, the polypeptide consists of SEQ ID NO: 497.

[0480]

[0473] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 498. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 498. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 498. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 498. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 498. In some embodiments, a polypeptide comprises SEQ ID NO: 498. In some embodiments, the polypeptide consists of SEQ ID NO: 498.

[0481]

[0474] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 499. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 499. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 499. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 499. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 499. In some embodiments, a polypeptide comprises SEQ ID NO: 499. In some embodiments, the polypeptide consists of SEQ ID NO: 499.

[0482]

[0475] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 500. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 500. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 500. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 500. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 500. In some embodiments, a polypeptide comprises SEQ ID NO: 500. In some embodiments, the polypeptide consists of SEQ ID NO: 500.

[0483]

[0476] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 501. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 501. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 501. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 501. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 501. In some embodiments, a polypeptide comprises SEQ ID NO: 501. In some embodiments, the polypeptide consists of SEQ ID NO: 501.

[0484]

[0477] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 502. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 502. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 502. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 502. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 502. In some embodiments, a polypeptide comprises SEQ ID NO: 502. In some embodiments, the polypeptide consists of SEQ ID NO: 502.

[0485]

[0478] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 503. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 503. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 503. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 503. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 503. In some embodiments, a polypeptide comprises SEQ ID NO: 503. In some embodiments, the polypeptide consists of SEQ ID NO: 503.

[0486]

[0479] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 504. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 504. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 504. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 504. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 504. In some embodiments, a polypeptide comprises SEQ ID NO: 504. In some embodiments, the polypeptide consists of SEQ ID NO: 504.

[0487]

[0480] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 505. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 505. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 505. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 505. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 505. In some embodiments, a polypeptide comprises SEQ ID NO: 505. In some embodiments, the polypeptide consists of SEQ ID NO: 505.

[0481] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 506. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 506. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 506. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 506. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 506. In some embodiments, a polypeptide comprises SEQ ID NO: 506. In some embodiments, the polypeptide consists of SEQ ID NO: 506.

[0488]

[0482] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 507. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 507. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 507. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 507. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 507. In some embodiments, a polypeptide comprises SEQ ID NO: 507. In some embodiments, the polypeptide consists of SEQ ID NO: 507.

[0489]

[0483] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 508. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 508. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 508. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 508. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 508. In some embodiments, a polypeptide comprises SEQ ID NO: 508. In some embodiments, the polypeptide consists of SEQ ID NO: 508.

[0490]

[0484] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 509. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 509. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 509. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 509. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 509. In some embodiments, a polypeptide comprises SEQ ID NO: 509. In some embodiments, the polypeptide consists of SEQ ID NO: 509.

[0491]

[0485] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 510. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 510. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 510. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 510. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 510. In some embodiments, a polypeptide comprises SEQ ID NO: 510. In some embodiments, the polypeptide consists of SEQ ID NO: 510.

[0492]

[0486] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 511. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 511. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 511. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 511. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 511. In some embodiments, a polypeptide comprises SEQ ID NO: 511. In some embodiments, the polypeptide consists of SEQ ID NO: 511.

[0493]

[0487] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 512. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 512. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 512. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 512. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 512. In some embodiments, a polypeptide comprises SEQ ID NO: 512. In some embodiments, the polypeptide consists of SEQ ID NO: 512.

[0494]

[0488] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 513. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 513. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 513. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 513. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 513. In some embodiments, a polypeptide comprises SEQ ID NO: 513. In some embodiments, the polypeptide consists of SEQ ID NO: 513.

[0495]

[0489] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 514. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 514. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 514. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 514. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 514. In some embodiments, a polypeptide comprises SEQ ID NO: 514. In some embodiments, the polypeptide consists of SEQ ID NO: 514.

[0496]

[0490] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 515. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 515. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 515. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 515. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 515. In some embodiments, a polypeptide comprises SEQ ID NO: 515. In some embodiments, the polypeptide consists of SEQ ID NO: 515.

[0497]

[0491] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 516. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 516. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 516. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 516. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 516. In some embodiments, a polypeptide comprises SEQ ID NO: 516. In some embodiments, the polypeptide consists of SEQ ID NO: 516.

[0498]

[0492] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 517. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 517. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 517. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 517. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 517. In some embodiments, a polypeptide comprises SEQ ID NO: 517. In some embodiments, the polypeptide consists of SEQ ID NO: 517.

[0499]

[0493] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 518. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 518. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 518. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 518. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 518. In some embodiments, a polypeptide comprises SEQ ID NO: 518. In some embodiments, the polypeptide consists of SEQ ID NO: 518.

[0500]

[0494] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 519. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 519. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 519. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 519. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 519. In some embodiments, a polypeptide comprises SEQ ID NO: 519. In some embodiments, the polypeptide consists of SEQ ID NO: 519.

[0501]

[0495] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 520. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 520. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 520. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 520. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 520. In some embodiments, a polypeptide comprises SEQ ID NO: 520. In some embodiments, the polypeptide consists of SEQ ID NO: 520.

[0502]

[0496] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 521. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 521. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 521. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 521. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 521. In some embodiments, a polypeptide comprises SEQ ID NO: 521. In some embodiments, the polypeptide consists of SEQ ID NO: 521.

[0503]

[0497] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 522. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 522. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 522. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 522. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 522. In some embodiments, a polypeptide comprises SEQ ID NO: 522. In some embodiments, the polypeptide consists of SEQ ID NO: 522.

[0504]

[0498] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 523. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 523. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 523. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 523. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 523. In some embodiments, a polypeptide comprises SEQ ID NO: 523. In some embodiments, the polypeptide consists of SEQ ID NO: 523.

[0505]

[0499] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 524. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 524. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 524. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 524. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 524. In some embodiments, a polypeptide comprises SEQ ID NO: 524. In some embodiments, the polypeptide consists of SEQ ID NO: 524.

[0500] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 525. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 525. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 525. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 525. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 525. In some embodiments, a polypeptide comprises SEQ ID NO: 525. In some embodiments, the polypeptide consists of SEQ ID NO: 525.

[0506]

[0501] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 526. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 526. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 526. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 526. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 526. In some embodiments, a polypeptide comprises SEQ ID NO: 526. In some embodiments, the polypeptide consists of SEQ ID NO: 526.

[0507]

[0502] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 527. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 527. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 527. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 527. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 527. In some embodiments, a polypeptide comprises SEQ ID NO: 527. In some embodiments, the polypeptide consists of SEQ ID NO: 527.

[0508]

[0503] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 528. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 528. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 528. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 528. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 528. In some embodiments, a polypeptide comprises SEQ ID NO: 528. In some embodiments, the polypeptide consists of SEQ ID NO: 528.

[0509]

[0504] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 529. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 529. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 529. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 529. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 529. In some embodiments, a polypeptide comprises SEQ ID NO: 529. In some embodiments, the polypeptide consists of SEQ ID NO: 529.

[0510]

[0505] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 530. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 530. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 530. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 530. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 530. In some embodiments, a polypeptide comprises SEQ ID NO: 530. In some embodiments, the polypeptide consists of SEQ ID NO: 530.

[0511]

[0506] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 531. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 531. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 531. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 531. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 531. In some embodiments, a polypeptide comprises SEQ ID NO: 531. In some embodiments, the polypeptide consists of SEQ ID NO: 531.

[0512]

[0507] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 532. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 532. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 532. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 532. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 532. In some embodiments, a polypeptide comprises SEQ ID NO: 532. In some embodiments, the polypeptide consists of SEQ ID NO: 532.

[0513]

[0508] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 533. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 533. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 533. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 533. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 533. In some embodiments, a polypeptide comprises SEQ ID NO: 533. In some embodiments, the polypeptide consists of SEQ ID NO: 533.

[0514]

[0509] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 534. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 534. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 534. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 534. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 534. In some embodiments, a polypeptide comprises SEQ ID NO: 534. In some embodiments, the polypeptide consists of SEQ ID NO: 534.

[0515]

[0510] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 535. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 535. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 535. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 535. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 535. In some embodiments, a polypeptide comprises SEQ ID NO: 535. In some embodiments, the polypeptide consists of SEQ ID NO: 535.

[0516]

[0511] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 536. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 536. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 536. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 536. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 536. In some embodiments, a polypeptide comprises SEQ ID NO: 536. In some embodiments, the polypeptide consists of SEQ ID NO: 536.

[0517]

[0512] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 537. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 537. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 537. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 537. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 537. In some embodiments, a polypeptide comprises SEQ ID NO: 537. In some embodiments, the polypeptide consists of SEQ ID NO: 537.

[0518]

[0513] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 538. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 538. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 538. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 538. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 538. In some embodiments, a polypeptide comprises SEQ ID NO: 538. In some embodiments, the polypeptide consists of SEQ ID NO: 538.

[0519]

[0514] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 539. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 539. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 539. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 539. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 539. In some embodiments, a polypeptide comprises SEQ ID NO: 539. In some embodiments, the polypeptide consists of SEQ ID NO: 539.

[0520]

[0515] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 540. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 540. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 540. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 540. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 540. In some embodiments, a polypeptide comprises SEQ ID NO: 540. In some embodiments, the polypeptide consists of SEQ ID NO: 540.

[0521]

[0516] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 541. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 541. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 541. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 541. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 541. In some embodiments, a polypeptide comprises SEQ ID NO: 541. In some embodiments, the polypeptide consists of SEQ ID NO: 541.

[0522]

[0517] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 542. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 542. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 542. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 542. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 542. In some embodiments, a polypeptide comprises SEQ ID NO: 542. In some embodiments, the polypeptide consists of SEQ ID NO: 542.

[0523]

[0518] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 543. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 543. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 543. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 543. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 543. In some embodiments, a polypeptide comprises SEQ ID NO: 543. In some embodiments, the polypeptide consists of SEQ ID NO: 543.

[0519] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 544. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 544. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 544. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 544. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 544. In some embodiments, a polypeptide comprises SEQ ID NO: 544. In some embodiments, the polypeptide consists of SEQ ID NO: 544.

[0524]

[0520] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 545. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 545. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 545. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 545. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 545. In some embodiments, a polypeptide comprises SEQ ID NO: 545. In some embodiments, the polypeptide consists of SEQ ID NO: 545. A polypeptide comprising the amino acid sequence of SEQ ID NO: 545 is also referred to herein as “HSA-53.” HSA-53 is a modified version of HSA-1 (SEQ ID NO: 493), which includes a W53D mutation in its Loop 2 sequence to reduce hydrophobicity and improve stability of the polypeptide while retaining its HSA binding properties.

[0525]

[0521] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 546. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 546. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 546. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 546. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 546. In some embodiments, a polypeptide comprises SEQ ID NO: 546. In some embodiments, the polypeptide consists of SEQ ID NO: 546. A polypeptide comprising the amino acid sequence of SEQ ID NO: 546 is also referred to herein as “HSA-54.” HSA-54 is a modified version of HSA-3 (SEQ ID NO: 495), which includes a A51L and L52R mutations in its Loop 2 sequence to improve both its affinity to the HSA protein and its PK profile in vivo.

[0526]

[0522] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 547. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 547. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 547. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 547. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 547. In some embodiments, a polypeptide comprises SEQ ID NO: 547. In some embodiments, the polypeptide consists of SEQ ID NO: 547.

[0523] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 548. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 548. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 548. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 548. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 548. In some embodiments, a polypeptide comprises SEQ ID NO: 548. In some embodiments, the polypeptide consists of SEQ ID NO: 548.

[0527]

[0524] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 549. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 549. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 549. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 549. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 549. In some embodiments, a polypeptide comprises SEQ ID NO: 549. In some embodiments, the polypeptide consists of SEQ ID NO: 549.

[0528]

[0525] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 550. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 550. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 550. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 550. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 550. In some embodiments, a polypeptide comprises SEQ ID NO: 550. In some embodiments, the polypeptide consists of SEQ ID NO: 550.

[0529]

[0526] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 551. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 551. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 551. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 551. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 551. In some embodiments, a polypeptide comprises SEQ ID NO: 551. In some embodiments, the polypeptide consists of SEQ ID NO: 551.

[0530]

[0527] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 552. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 552. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 552. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 552. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 552. In some embodiments, a polypeptide comprises SEQ ID NO: 552. In some embodiments, the polypeptide consists of SEQ ID NO: 552.

[0531]

[0528] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 553. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 553. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 553. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 553. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 553. In some embodiments, a polypeptide comprises SEQ ID NO: 553. In some embodiments, the polypeptide consists of SEQ ID NO: 553.

[0532]

[0529] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 554. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 554. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 554. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 554. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 554. In some embodiments, a polypeptide comprises SEQ ID NO: 554. In some embodiments, the polypeptide consists of SEQ ID NO: 554.

[0533]

[0530] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 555. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 555. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 555. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 555. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 555. In some embodiments, a polypeptide comprises SEQ ID NO: 555. In some embodiments, the polypeptide consists of SEQ ID NO: 555.

[0534]

[0531] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 556. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 556. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 556. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 556. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 556. In some embodiments, a polypeptide comprises SEQ ID NO: 556. In some embodiments, the polypeptide consists of SEQ ID NO: 556.

[0535]

[0532] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 557. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 557. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 557. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 557. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 557. In some embodiments, a polypeptide comprises SEQ ID NO: 557. In some embodiments, the polypeptide consists of SEQ ID NO: 557.

[0536]

[0533] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 558. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 558. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 558. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 558. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 558. In some embodiments, a polypeptide comprises SEQ ID NO: 558. In some embodiments, the polypeptide consists of SEQ ID NO: 558.

[0537]

[0534] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 559. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 559. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 559. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 559. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 559. In some embodiments, a polypeptide comprises SEQ ID NO: 559. In some embodiments, the polypeptide consists of SEQ ID NO: 559.

[0538]

[0535] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 560. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 560. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 560. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 560. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 560. In some embodiments, a polypeptide comprises SEQ ID NO: 560. In some embodiments, the polypeptide consists of SEQ ID NO: 560.

[0539]

[0536] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 561. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 561. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 561. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 561. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 561. In some embodiments, a polypeptide comprises SEQ ID NO: 561. In some embodiments, the polypeptide consists of SEQ ID NO: 561.

[0540]

[0537] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 562. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 562. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 562. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 562. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 562. In some embodiments, a polypeptide comprises SEQ ID NO: 562. In some embodiments, the polypeptide consists of SEQ ID NO: 562.

[0541]

[0538] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 563. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 563. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 563. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 563. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 563. In some embodiments, a polypeptide comprises SEQ ID NO: 563. In some embodiments, the polypeptide consists of SEQ ID NO: 563.

[0542]

[0539] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 564. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 564. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 564. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 564. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 564. In some embodiments, a polypeptide comprises SEQ ID NO: 564. In some embodiments, the polypeptide consists of SEQ ID NO: 564.

[0543]

[0540] In some embodiments, a polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 565. In some embodiments, a polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 565. In some embodiments, a polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 565. In some embodiments, a polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 565. In some embodiments, a polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 565. In some embodiments, a polypeptide comprises SEQ ID NO: 565. In some embodiments, the polypeptide consists of SEQ ID NO: 565.

[0544]

[0541] In some embodiments, a fusion protein comprises a polypeptide (e.g., AFFIMER® polypeptide) that binds specifically to FAP and a polypeptide (e.g., AFFIMER® polypeptide) that binds specifically to HSA. In some embodiments, a fusion protein comprises two polypeptides (e.g., AFFIMER® polypeptides) each binding specifically to FAP and a polypeptide (e.g., AFFIMER® polypeptide) that binds specifically to HSA. In some embodiments, a fusion protein comprises a polypeptide (e.g., AFFIMER® polypeptide) that binds specifically to FAP and two polypeptides (e.g., AFFIMER® polypeptides) each binding specifically to HSA. In some embodiments, a fusion protein comprises two polypeptides (e.g., AFFIMER® polypeptides) each binding specifically to FAP and two polypeptides (e.g., AFFIMER® polypeptides) each binding specifically to HSA. Thus, in some embodiments, a fusion protein comprises one or more polypeptide that binds specifically to FAP and one or more polypeptide that binds specifically to HSA. Such fusion proteins, in some embodiments, include one or more cysteine residue (e.g., one, two, three, or more) to which an agent may be linked. Such cysteine residues can be located in any one or more regions of an AFFIMER® polypeptide, for example, selected from an N- terminus region, a C-terminus region, a Loop 3 (or Loop 7) region (e.g., between a Loop 2 and a Loop 4 binding region), and a linker region. Exemplary fusion proteins sequences are provided in Tables 11 and 12.

[0545] Table 11. Exemplary FAP / HSA Multimer Protein Sequences

[0546] Table 12. Exemplary FAP / HSA Multimer Protein Sequences with Cysteine Modifications

[0547]

[0548]

[0549]

[0542] In some embodiments, the polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 566. In some embodiments, the polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 566. In some embodiments, the polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 566. In some embodiments, the polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 566. In some embodiments, the polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 566. In some embodiments, the polypeptide comprises SEQ ID NO: 566. In some embodiments, the polypeptide consists of SEQ ID NO: 566.

[0543] In some embodiments, the polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 567. In some embodiments, the polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 567. In some embodiments, the polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 567. In some embodiments, the polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 567. In some embodiments, the polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 567. In some embodiments, the polypeptide comprises SEQ ID NO: 567. In some embodiments, the polypeptide consists of SEQ ID NO: 567.

[0550]

[0544] In some embodiments, the polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 568. In some embodiments, the polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 568. In some embodiments, the polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 568. In some embodiments, the polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 568. In some embodiments, the polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 568. In some embodiments, the polypeptide comprises SEQ ID NO: 568. In some embodiments, the polypeptide consists of SEQ ID NO: 568.

[0551]

[0545] In some embodiments, the polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 569. In some embodiments, the polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 569. In some embodiments, the polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 569. In some embodiments, the polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 569. In some embodiments, the polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 569. In some embodiments, the polypeptide comprises SEQ ID NO: 569. In some embodiments, the polypeptide consists of SEQ ID NO: 569.

[0552]

[0546] In some embodiments, the polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 570. In some embodiments, the polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 570. In some embodiments, the polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 570. In some embodiments, the polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 570. In some embodiments, the polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 570. In some embodiments, the polypeptide comprises SEQ ID NO: 570. In some embodiments, the polypeptide consists of SEQ ID NO: 570.

[0553]

[0547] In some embodiments, the polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 571. In some embodiments, the polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 571. In some embodiments, the polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 571. In some embodiments, the polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 571. In some embodiments, the polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 571. In some embodiments, the polypeptide comprises SEQ ID NO: 571. In some embodiments, the polypeptide consists of SEQ ID NO: 571.

[0554]

[0548] In some embodiments, the polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 572. In some embodiments, the polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 572. In some embodiments, the polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 572. In some embodiments, the polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 572. In some embodiments, the polypeptide comprises an amino acid sequence having at least 98% identity to SEQ ID NO: 572. In some embodiments, the polypeptide comprises SEQ ID NO: 572. In some embodiments, the polypeptide consists of SEQ ID NO: 572.

[0555]

[0549] In some embodiments, the polypeptide comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 573. In some embodiments, the polypeptide comprises an amino acid sequence having at least 85% identity to SEQ ID NO: 573. In some embodiments, the polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 573. In some embodiments, the polypeptide comprises an amino acid sequence having at least 95%...

Claims

CLAIMSWhat is claimed is:

1. A polypeptide comprising: an amino acid sequence having at least 90% identity to the sequence of MGIPGGLSEAKPATPEIQEIVDKVKPQLEEKTGETYGKLEAVQYKTQVWTNYYIKVRAGDN KYMHLKVFKSLX2EDLVLTGYQVDKNKDDELTGF (SEQ ID NO: 2), wherein X}is a first peptide comprising the amino acid sequence of any of SEQ ID NOs: 5-108 and X2 is a second peptide sequence comprising the amino acid sequence of any of SEQ ID NOs: 109-212.

2. The polypeptide of claim 1, comprising an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 2.

3. The polypeptide of claim 2, comprising the sequence of SEQ ID NO: 2.

4. The polypeptide of any preceding claim, wherein the polypeptide binds specifically to fibroblast activation protein alpha (FAPa) with a Kd of 1x106M or less.

5. The polypeptide of any one of claims 1-4, comprising an amino acid sequence having at least 90%, at least 95% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 213-316.

6. The polypeptide of any one of claims 1-4, wherein the first peptide comprises the amino acid sequence of SEQ ID NO: 5, and the second peptide comprises the amino acid sequence of SEQ ID NO: 109.

7. The polypeptide of claim 6, comprising the amino acid sequence of SEQ ID NO: 213.

8. The polypeptide of any one of claims 1-4, wherein the first peptide comprises the amino acid sequence of SEQ ID NO: 6, and the second peptide comprises the amino acid sequence of SEQ ID NO: 110.

9. The polypeptide of claim 8, comprising the amino acid sequence of SEQ ID NO: 214.

10. The polypeptide of any preceding claim, wherein the amino acid sequence of the polypeptide comprises one or more cysteine (C).

11. The polypeptide of claimlO, wherein the one or more C is in an N-terminal region of the polypeptide, optionally within 10 amino acids of the N terminus of the polypeptide.

12. The polypeptide of claim 10 or 11, wherein the one or more C is in a C-terminal region of the polypeptide, optionally within 10 amino acids of the C terminus of the polypeptide.

13. The polypeptide of any one of claims 10-12, wherein the one or more C is in a Loop 3 region of the polypeptide between Xi and X2.

14. A fusion protein comprising two or more of the polypeptides of any preceding claim.

15. The fusion protein of claim 14, comprising an amino acid sequence having at least 90%, at least 95% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 317-334.

16. A fusion protein comprising the polypeptide of any preceding claim and an additional polypeptide.

17. The fusion protein of claim 16, wherein the additional polypeptide of the fusion protein is a half-life extension protein or molecule.

18. The fusion protein of claim 17, wherein half-life extension protein is selected from an (i) Fc region of an antibody, (ii) transferrin, and (iii) albumin.

19. The fusion protein of claim 18, wherein the additional polypeptide comprises an amino acid sequence having at least 90% identity to the sequence of MGIPGGLSEAKPATPEIQEIVDKVKPQLEEKTGETYGKLEAVQYKTQVX / TNYYIKVRAGDN KYMHLKVFKSLX2EDLVLTGYQVDKNKDDELTGF (SEQ ID NO: 2), wherein Xi is a first peptide comprising the amino acid sequence of any of SEQ ID NOs: 389-440, 764, or 765, and X2 is a second peptide sequence comprising the amino acid sequence of any of SEQ ID NOs: 441-492, 766, or 767.

20. The fusion protein of claim 19, wherein the additional polypeptide comprises an amino acid sequence having at least 95% identity to the sequence of SEQ ID NO: 2.

21. The fusion protein of claim 20, wherein the additional polypeptide comprises the sequence of SEQ ID NO: 2.

22. The fusion protein of any preceding claim, wherein the additional polypeptide binds specifically to human serum albumin (HSA) with a Kd of 1x106M or less.

23. The fusion protein of any preceding claim, wherein the additional polypeptide comprises an amino acid sequence having at least 90%, at least 95% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 493-546.

24. The fusion protein of any preceding claim, wherein the additional polypeptide comprises an amino acid sequence having at least 90%, at least 95% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 547-556.

25. The fusion protein of claim 24, wherein the additional polypeptide comprises the amino acid sequence of SEQ ID NO: 493, 494, or 495.

26. The fusion protein of claim 24, wherein the additional polypeptide comprises the amino acid sequence of SEQ ID NO: 545 or 546.

27. The fusion protein of claim 24, wherein the additional polypeptide comprises the amino acid sequence of SEQ ID NO: 556.

28. The fusion protein of any preceding claim, comprising an amino acid sequence having at least 90%, at least 95% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 566-573.

29. The fusion protein of any preceding claim, wherein the amino acid sequence of the additional polypeptide comprises one or more cysteine (C).

30. The fusion protein of claim 29, wherein the one or more C is in an N-terminal region of the additional polypeptide, optionally within 10 amino acids of the N terminus of the additional polypeptide, and / or wherein the one or more C is in a C-terminal region of the additional polypeptide, optionally within 10 amino acids of the C terminus of the additional polypeptide.

31. The fusion protein of claim 29, wherein the one or more C is within a linker region linking two or more polypeptides of the fusion protein to each other.

32. The fusion protein of any one of claims 29-31 , wherein the one or more C is in a Loop 3 region of the additional polypeptide between Xi and X2.

33. A polypeptide comprising: an amino acid sequence having at least 90% identity to the sequence of MGIPGGLSEAKPATPEIQEIVDKVKPQLEEKTGETYGKLEAVQYKTQVX / TNYYIKVRAGDN KYMHLKVFKSLX2EDLVLTGYQVDKNKDDELTGF (SEQ ID NO: 2) modified to include one or more cysteine (C) substitution or addition, wherein Xi is a first peptide comprising the amino acid sequence of any of SEQ ID NOs: 5-108 and X2 is a second peptide sequence comprising the amino acid sequence of any of SEQ ID NOs: 109-212.

34. A polypeptide comprising: an amino acid sequence having at least 90% identity to the sequence of MGIPGGLSEAKPATPEIQEIVDKVKPQLEEKTGETYGKLEAVQYKTQVX / TNYYIKVRAGDN KYMHLKVFKSLX2EDLVLTGYQVDKNKDDELTGF (SEQ ID NO: 2) modified to include one or more cysteine (C) substitution or addition, wherein Xi is a first peptide comprising the amino acid sequence of any of SEQ ID NOs: 389-440, 764, or 765, and X2 is a second peptide sequence comprising the amino acid sequence of any of SEQ ID NOs: 441-492, 766, or 767.

35. A polypeptide comprising an amino acid sequence having at least 90%, at least 95%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 335-352.

36. A polypeptide comprising an amino acid sequence having at least 90%, at least 95%, or 100% identity to the amino acid sequence of SEQ ID NO: 557 or 558.

37. A fusion protein comprising an amino acid sequence having at least 90%, at least 95%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 353-388.

38. A fusion protein comprising an amino acid sequence having at least 90%, at least 95%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 559-565.

39. A fusion protein comprising an amino acid sequence having at least 90%, at least 95%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 574-605, or 768-782.

40. The polypeptide or fusion protein of any preceding claim conjugated to one or more moiety of interest via the one or more cysteine.

41. A protein conjugate comprising the polypeptide or the fusion protein of any preceding claim and a moiety of interest, optionally conjugated to the polypeptide or the fusion protein via one or more cysteine residues, optionally wherein the moiety of interest is selected from small molecule drugs or prodrugs.

42. A polynucleotide comprising an open reading frame encoding the polypeptide, the fusion protein, or the protein conjugate of any preceding claim.

43. A method comprising administering the polypeptide, the fusion protein, the protein conjugate, or the polynucleotide of any preceding claim to a subject in need thereof, optionally, wherein the subject has a cancer.

44. The polypeptide, the fusion protein, the protein conjugate, or the polynucleotide of any preceding claim for use in a method for treating or diagnosing cancer.

45. Use of the polypeptide, the fusion protein, the protein conjugate, or the polynucleotide of any preceding claim in the manufacture of a medicament for the treatment of cancer.

46. The method of claim 33 or 34, wherein the tumor tissue is from a cancer listed in Table 21 or 22.

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