Synthetic receptors for control and specific treatment of renal cell carcinoma with car t cells

Abstract

Provided herein are antibodies and antibody fragments that bind CA9 or ENPP3. Also provided are methods of treating clear cell renal cell carcinoma with an antibody or antibody fragment that binds CA9 and an antibody or antibody fragment that binds ENPP3.

Description

WSGR Docket Number: 63580-708.601SYNTHETIC RECEPTORS FOR CONTROL AND SPECIFIC TREATMENT OF RENAL CELL CARCINOMA WITH CAR T CELLS CROSS-REFERENCE

[0001] This application claims the benefit of US Provisional Application Serial Number 63 / 714,044 filed on October 30, 2024; US Provisional Application Serial Number 63 / 796,912 filed on April 29, 2025; and US Provisional Application Serial Number 63 / 862,247 filed on August 12, 2025, the entirety of which is hereby incorporated by reference herein.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on October 27, 2025, is named Linked Cell 63580-708_601_SL.xml and is 2,632,940 bytes in size.BACKGROUND

[0003] Current T cells therapies, such as involving T cells expressing chimeric antigen receptors (CARs), are often limited by target expression. An ideal target for conventional CAR T cells would be a target expressed in a cancer cell and no or very low expression in healthy cells. Current CAR T cell therapies may have off-tumor on-target toxicity due to CAR T cell cytotoxicity of normal tissues. Consequently, there remains a need for advancements in CAR T cell therapies.SUMMARY

[0004] Described herein, in some aspects, is a pharmaceutical composition comprising a first fusion protein comprising an antibody or antibody fragment that binds ENPP3, and a second fusion protein comprising an antibody or antibody fragment that binds CA9, wherein: the antibody or antibody fragment that binds ENPP3 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 2668; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 2669; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 2670; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 2671; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 2672; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 2673; (ii) a variable heavy domain of heavy chain (VHH) comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 2106; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 2107; and a CDRH3WSGR Docket Number: 63580-708.601 comprising the amino acid sequence of SEQ ID NO: 2108; or (iii) a variable heavy domain of heavy chain (VHH) comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 2109; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 2110; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 211 l;and the antibody or antibody fragment that binds CA9 comprises a variable heavy domain of heavy chain (VHH) comprising: (i) a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1241; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 1242; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 1243; (ii) a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1307; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 1308; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 1309. In some embodiments, the first fusion protein comprises a LAT polypeptide and the second fusion protein comprises a SLP76 polypeptide. In some embodiments, the LAT polypeptide comprises any one of SEQ ID NOS: 2714, 2715, 2723, 2724, or 3007-3014; and the SLP76 polypeptide comprises SEQ ID NO: 2712 or 2713. In some embodiments, the LAT polypeptide comprises SEQ ID NO: 3009, optionally wherein the LAT polypeptide does not comprise amino acids 1-63 of SEQ ID NO: 2723 or amino acids 173-235 of SEQ ID NO: 2723; and the SLP76 polypeptide comprises SEQ ID NO: 2712. In some embodiments, the antibody or antibody fragment that binds CA9 comprises (b)(i), and the VHH has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168. In some embodiments, the antibody or antibody fragment that binds CA9 comprises (b)(i), and the VHH has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1190. In some embodiments, the antibody or antibody fragment that binds ENPP3 comprises (a)(ii), and the VHH has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2035. In some embodiments, the antibody or antibody fragment that binds ENPP3 comprises (a)(iii), and the VHH has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2036. In some embodiments, the antibody or antibody fragment that binds ENPP3 comprises (a)(i), and the light chain variable region (VL) has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and the heavy chain variable region (VH) has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the antibody or antibody fragment that binds ENPP3 comprises (a)(i), and a sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2449 or SEQ ID NO: 3000. In some embodiments, the antibody or antibody fragment that binds ENPP3 does notWSGR Docket Number: 63580-708.601 bind to a cell with low expression of ENPP3, and the antibody or antibody fragment that binds CA9 does not bind to a cell with low expression of CA9.

[0005] Described herein, in some aspects, is a pharmaceutical composition comprising: a first chimeric antigen receptor (CAR) polypeptide comprising: an antibody or antibody fragment having a binding affinity for a CA9 protein; a first transmembrane domain; and a first intracellular signaling domain; and a second chimeric antigen receptor (CAR) polypeptide comprising: an antibody or antibody fragment having a binding affinity for an ENPP3 protein; a second transmembrane domain; and a second intracellular signaling domain different from the first ligand, wherein the binding affinity for the CA9 protein is lower compared to the binding affinity for the ENPP3 protein. In some embodiments, the binding affinity for the CA9 protein is between about 10 micromolar to about 1 micromolar. In some embodiments, the binding affinity for the ENPP3 protein is between about 50 x 1 O’9M, to about 5 x 1 O’9M. In some embodiments, the binding affinity for the CA9 protein comprises a dissociation rate constant (koff) between about 1.0 x 10'3S'1to about 5.0 x 10'3S'1. In some embodiments, the binding affinity for the CA9 protein comprises a dissociation rate constant (koff) between about 1.0 x 10'4S'1to about 5.0 x 10'4S'1. In some embodiments, the binding affinity for the CA9 protein comprises a dissociation rate constant (koff) between about 1.0 x 10'5S'1to about 5.0 x 10'5S'1. In some embodiments, the binding affinity for the ENPP3 protein comprises a dissociation rate constant (koff) between about 1.0 x 10'3S'1to about 5.0 x 10'3S'1. In some embodiments, the binding affinity for the ENPP3 protein comprises a dissociation rate constant (koff) between about 1.0 x 10'4S'1to about 5.0 x 10'4S'1. In some embodiments, the binding affinity for the ENPP3 protein comprises a dissociation rate constant (koff) between about 1.0 x 10'5S'1to about 5.0 x 10'5S'1. In some embodiments, the binding affinity for the ENPP3 protein comprises a dissociation rate constant (koff) of about 1.0 x 10'6S'1, about 2.0 x 10'6S'1, about 3.0 x 10'6S'1, about 4.0 x 10'6S'1, or about 5.0 x 10'6S'1. In some embodiments, binding of the first extracellular ligandbinding domain to the CA9 protein, in absence of binding of the second extracellular ligandbinding domain to the ENPP3 protein, does not activate the first intracellular signaling domain. In some embodiments, the antibody or antibody fragment that binds ENPP3 does not bind to a cell with low expression of ENPP3, and the antibody or antibody fragment that binds CA9 does not bind to a cell with low expression of CA9.

[0006] Described herein, in some aspects, is a nucleic acid composition comprising a nucleic acid encoding the first fusion protein described herein, and a nucleic acid encoding the second fusion protein described herein. In some embodiments, the nucleic acid composition is a viral vector.WSGR Docket Number: 63580-708.601

[0007] Described herein, in some aspects, is a lymphocyte comprising the pharmaceutical composition described herein, or the nucleic acid composition described herein. In some embodiments, the lymphocyte is a T cell, a NK cell, or a NKT cell.

[0008] Described herein

[0009] A method of inhibiting proliferation of a cell expressing CA9 and ENPP3, the method comprising: contacting a cell with the pharmaceutical composition of any one of claims 1-22, the nucleic acid composition of claim 23 or claim 24, or the lymphocyte of claim 25 or claim 26.

[0010] A method of treating clear cell renal cell carcinoma, the method comprising administering to a subject in need thereof the pharmaceutical composition described herein, the nucleic acid composition described herein, or the lymphocyte described herein. In some embodiments, prior to the administering, the subject was treated with a cancer therapy. In some embodiments, the cancer therapy comprises an immuno-oncology therapy, a tyrosine kinase inhibitor, or a HIF inhibitor, or a combination of two or more thereof. In some embodiments, prior to the administering, the CA9 and / or the ENPP3 is detected from a sample obtained from the subject, optionally wherein the CA9 or the ENPP3 is detected using immunohistochemistry or positron emission tomography.

[0011] Provided herein is an antibody or antibody fragment that binds CA9, wherein the antibody or antibody fragment comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1241; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1242; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1243. In some embodiments, the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168.

[0012] Provided herein is an antibody or antibody fragment that binds CA9, wherein the antibody or antibody fragment comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1307; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1308; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1309. In some embodiments, the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1190.WSGR Docket Number: 63580-708.601

[0013] Provided herein is an antibody or antibody fragment that binds ENPP3, wherein the antibody or antibody fragment comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 2106; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 2107; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 2108. In some embodiments, the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2035.

[0014] Provided herein is an antibody or antibody fragment that binds ENPP3, wherein the antibody or antibody fragment comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 2109; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 2110; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 2111. In some embodiments, the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2036.

[0015] Provided herein is an antibody or antibody fragment that binds ENPP3, wherein the antibody or antibody fragment comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 2668; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 2669; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 2670; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 2671; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 2672; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 2673. In some embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2449. In someWSGR Docket Number: 63580-708.601 embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000.

[0016] Provided herein is an antibody or antibody fragment that binds CA9, wherein the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1370; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1371; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1372; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1373; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1374; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1375; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1376; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1377; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1378; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1379; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1380; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1381; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1382; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1383; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1384; or a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1385. In some embodiments, the antibody or antibody fragment comprises the CDR1-3 of any one of SEQ ID NOS: 1386-1388, 1389-1391, 1392-1394, 1395-1397, 1398-WSGR Docket Number: 63580-708.6011400, 1401-1403, 1404-1406, 1407-1409, 1410-1412, 1413-1415, 1416-1418, 1419-1421, 1422- 1424, 1425-1427, 1428-1430, and 1431-1433, wherein the CDR1-3 are selected from within the same antibody and antibody fragment clone.

[0017] Provided herein is an antibody or antibody fragment that binds ENPP3, wherein the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2310; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2311; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2312; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2313; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2314; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2315; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2316; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2317; a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2318; or a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2319. In some embodiments, the antibody or antibody fragment comprises the CDR1-3 of any one of SEQ ID NOS: 2320-2322, 2323-2325, 2326- 2328, 2329-2331, 2332-2334, 2335-2337, 2338-2340, 2341-2343, 2344-2346, and 2347-2349, wherein the CDR1-3 are selected from within the same antibody and antibody fragment clone.

[0018] In some embodiments, the antibody or antibody fragment comprises a single chain variable fragment (scFv). In some embodiments, the antibody or antibody fragment comprises a variable heavy domain of heavy chain (VHH) antibody or antibody fragment.

[0019] Provided herein is an antibody or antibody fragment that binds CA9, wherein the antibody or antibody fragment comprises a single chain variable fragment (scFv), wherein the single chain variable fragment (scFv) comprises a sequence that has at least at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of sequences according to Tables 2-5.WSGR Docket Number: 63580-708.601

[0020] Provided herein is an antibody or antibody fragment that binds CA9, wherein the antibody or antibody fragment comprises a variable heavy domain of heavy chain (VHH) antibody or antibody fragment, wherein the VHH comprises a sequence that has at least at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of sequences according to Tables 6-11. In some embodiments, the VHH comprises a sequence that has at least at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583. In some embodiments, the VHH comprises a sequence that has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168.

[0021] Provided herein is an antibody or antibody fragment that binds ENPP3, wherein the antibody or antibody fragment comprises a single chain variable fragment (scFv), wherein the single chain variable fragment (scFv) comprises a sequence that has at least at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of sequences according to Tables 12-13. In some embodiments, the scFv comprises a sequence that has at least at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 3000.

[0022] Provided herein is an antibody or antibody fragment that binds ENPP3, wherein the antibody or antibody fragment comprises a variable heavy domain of heavy chain (VHH) antibody or antibody fragment, wherein the VHH comprises a sequence that has at least at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of sequences according to Tables 14-19.

[0023] In some embodiments, the antibody or antibody fragment binds to a CA9 protein with an affinity equal to or less than 1 micromolar. In some embodiments, the antibody or antibody fragments binds to a CA9 protein with an affinity equal to or less than 25 x 10-9 M (e.g., 5 10- 9 M). In some embodiments, the antibody or antibody fragment binds to a CA9 protein with an affinity equal to or less than 10 x 10-9 M (e.g., 1 x 10-9 M). In some embodiments, the antibody or antibody binds to a CA9 protein with an affinity equal to or less than 5 x 10-9 M (e.g., 1 x 10-9 M). In some embodiments, the antibody or antibody fragment comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583. In some embodiments, the VHH comprises a sequence that has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168.

[0024] In some embodiments, the antibody or antibody fragment binds to a ENPP3 protein with an affinity equal to or less than 50 x 10-9 M (e.g., 5 x 10-9 M). In some embodiments, the antibody or antibody fragment binds to a ENPP3 protein with an affinity equal to or less than 25WSGR Docket Number: 63580-708.601 x 10-9 M (e.g., 5 x 10-9 M). In some embodiments, the antibody or antibody fragment binds to a ENPP3 protein with an affinity equal to or less than 10 x 10-9 M (e.g., 1x10-9 M). In some embodiments, the antibody or antibody fragment binds to a ENPP3 protein with an affinity equal to or less than 5 x 10-9 M (e.g., 1 x 10-9 M). In some embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000.

[0025] In some embodiments, the CA9 protein comprises the amino acid sequence of SEQ ID NO: 2710.

[0026] In some embodiments, the ENPP3 protein comprises the amino acid sequence of SEQ ID NO: 2710.

[0027] In some embodiments, the antibody or antibody fragment binds to a cell expressing a CA9 protein.

[0028] In some embodiments, the antibody or antibody fragment binds to a cell expressing a ENPP3 protein. In some embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000.

[0029] In some embodiments, the antibody or antibody fragment binds to a cell expressing a CA9 and a ENPP3 protein. In some embodiments, the antibody or antibody fragment does not bind to a cell with no expression or low expressing of a CA9 protein. In some embodiments, the antibody or antibody fragment does not bind to a cell with no expression or low expressing of a ENPP3 protein.

[0030] Provided herein is a composition comprising the antibody or antibody fragment that binds CA9 and the antibody or antibody fragment that binds ENPP3. Provided herein is a composition comprising a nucleic acid encoding the antibody or antibody fragment that binds CA9, and a nucleic acid encoding the antibody or antibody fragment that binds ENPP3. In some embodiments, the composition is a lymphocyte such as a T cell, Natural killer (NK) cell, orWSGR Docket Number: 63580-708.601Natural killer T (NKT) cell. In some embodiments, the T cell is a CAR T cell. In some embodiments, the composition comprises the antibody or antibody fragment that binds CA9 fused to a SLP76 peptide. In some embodiments, the antibody or antibody fragment comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583. In some embodiments, the antibody or antibody fragment comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168. In some embodiments, the SLP76 peptide comprises SEQ ID NO: 2712, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 2712. In some embodiments, the SLP76 peptide consists or consists essentially of SEQ ID NO: 2712.

[0031] In some embodiments, the composition comprises the antibody or antibody fragment that binds ENPP3 fused to a LAT peptide. In some embodiments, the ENPP3 antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 3009. In some embodiments, the LAT peptide consists or consists essentially of SEQ ID NO: 3009. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, and does not comprise amino acids 1-63 of SEQ ID NO: 2723 or amino acids 173-235 of SEQ ID NO: 2723.

[0032] Provided herein is a pharmaceutical composition comprising: an antibody and antibody fragment comprising means for binding CA9; an antibody and antibody fragment comprising means for binding ENPP3; and a pharmaceutically acceptable carrier. In some embodiments, the means for binding ENPP3 comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the means for binding ENPP3 comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000. In some embodiments, the means for binding CA9 comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583. In some embodiments, the means for binding ENPP3WSGR Docket Number: 63580-708.601 comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168.

[0033] Provided herein is a method of inhibiting proliferation of a cell expressing CA9, the method comprising: contacting a cell with the antibody or antibody fragment or the pharmaceutical composition.

[0034] Provided herein is a method of inhibiting proliferation of a cell expressing ENPP3, the method comprising: contacting a cell with the antibody or antibody fragment or the pharmaceutical composition. In some embodiments, the ENPP3 antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000.

[0035] Provided herein is a method of inhibiting proliferation of a cell expressing CA9 and ENPP3, the method comprising: contacting a cell with the antibody or antibody fragment or the pharmaceutical composition. In some embodiments, the ENPP3 antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000. In some embodiments, the antibody or antibody fragment comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583. In some embodiments, the antibody or antibody fragment comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168.

[0036] Provided herein is a method of treating clear cell renal cell carcinoma, the method comprising administering to a subject in need thereof the antibody or antibody fragment, or the pharmaceutical composition. In some embodiments, prior to the administering, the subject was treated with a cancer therapy. In some embodiments, the cancer therapy comprises an immunooncology therapy, a tyrosine kinase inhibitor, or a HIF inhibitor, or a combination of two or more thereof. In some embodiments, prior to the administering, the subject is CA9 and / orWSGR Docket Number: 63580-708.601ENPP3 is detected from a sample from the subject. In some embodiments, the CA9 and / or ENPP3 is detected using immunohistochemistry or positron emission tomography. In some embodiments, the CA9 and / or ENPP3 is detected using an anti-CA9 and / or ENPP3 antibody or antibody fragment thereof of a table provided herein.

[0037] Provided herein is a method of detecting CA9 in a sample from the subject, the method comprising applying an antibody or antigen-binding fragment thereof specific to CA9 from a table provided herein to the sample from the subject. Provided herein is a method of detecting ENPP3 in a sample from the subject, the method comprising applying an antibody or antigenbinding fragment thereof specific to ENPP3 from a table provided herein to the sample from the subject. In some embodiments, the detecting comprises immunohistochemistry or positron emission tomography.

[0038] Provided herein is a method of treating clear cell renal carcinoma (ccRCC) in a subject in need thereof, the method comprising administering to the subject a first antibody or antibody fragment that binds to CA9 and a second antibody or antibody fragment that binds to ENPP3. In some embodiments, the antibody or antibody fragment that binds to CA9 comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583. In some embodiments, the antibody or antibody fragment that binds to CA9 comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168. In some embodiments, the ENPP3 antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000. In some embodiments, the antibody or antibody fragment that binds to CA9 is a means for binding CA9 and the antibody or antibody fragment that binds to ENPP3 is a means for binding ENPP3. In some embodiments, the administering comprises administering a lymphocyte such as a T cell, NK cell, or NKT cell comprising the first antibody and the second antibody. In some embodiments, the administering comprises administering to the subject a first fusion protein comprising the first antibody or antibody fragment that binds to CA9 connected to a first signaling domain, optionally via one or more linkers and a first transmembrane domain. In some embodiments, the first signaling domain comprises SLP76. In some embodiments, the SLP76 comprises SEQ ID NO: 2712, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 2712. In someWSGR Docket Number: 63580-708.601 embodiments, the SLP76 consists or consists essentially of SEQ ID NO: 2712. In some embodiments, the administering comprises administering to the subject a second fusion protein comprising the second antibody or antibody fragment that binds to ENPP3 connected to a second signaling domain, optionally via one or more linkers and a second transmembrane domain. In some embodiments, the second signaling domain comprises LAT. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 3009. In some embodiments, the LAT peptide consists or consists essentially of SEQ ID NO: 3009. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, and does not comprise amino acids 1-63 of SEQ ID NO: 2723 or amino acids 173-235 of SEQ ID NO: 2723. The first and the second fusion protein may independently have a formula disclosed herein.

[0039] Provided herein is a method of treating clear cell renal carcinoma (ccRCC) in a subject in need thereof, the method comprising administering to the subject a first expression construct encoding a first antibody or antibody fragment that binds to CA9 and a second expression construct encoding a second antibody or antibody fragment that binds to ENPP3. In some embodiments, the antibody or antibody fragment comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583. In some embodiments, the antibody or antibody fragment comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168. In some embodiments, the ENPP3 antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000. In some embodiments, the antibody or antibody fragment that binds to CA9 is a means for binding CA9 and the antibody or antibody fragment that binds to ENPP3 is a means for binding ENPP3. In some embodiments, the administering comprises administering a lymphocyte such as a T cell, NK cell, or NKT cell comprising the first expression construct and the second expression construct. In some embodiments, the first expression construct encodes a first fusion protein comprising the first antibody or antibody fragment that binds to CA9 connected to a first signaling domain, optionally via one or more linkers and a first transmembrane domain. In some embodiments, the first signaling domain comprises SLP76. In some embodiments, the SLP76 peptide comprises SEQ ID NO: 2712, or a sequence having 1, 2, 3, 4, or 5 amino acids differentWSGR Docket Number: 63580-708.601 than SEQ ID NO: 2712. In some embodiments, the SLP76 peptide consists or consists essentially of SEQ ID NO: 2712. In some embodiments, the second expression construct encodes a second fusion protein comprising the second antibody or antibody fragment that binds to ENPP3 connected to a second signaling domain, optionally via one or more linkers and a second transmembrane domain. In some embodiments, the second signaling domain comprises LAT. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 3009. In some embodiments, the LAT peptide consists or consists essentially of SEQ ID NO: 3009. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, and does not comprise amino acids 1-63 of SEQ ID NO: 2723 or amino acids 173-235 of SEQ ID NO: 2723. The first and the second fusion protein may independently have a formula disclosed herein.

[0040] Provided herein is a method of treating clear cell renal carcinoma (ccRCC) in a subject in need thereof, the method comprising administering to the subject an expression construct encoding a chimeric antigen receptor (CAR) construct encoding a first antibody or antibody fragment that binds to CA9 and a second antibody or antibody fragment that binds to ENPP3. In some embodiments, the ENPP3 antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000. In some embodiments, the CA9 antibody or antibody fragment comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583. In some embodiments, the CA9 antibody or antibody fragment comprises: a VHH having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168. In some embodiments, the antibody or antibody fragment that binds to CA9 is a means for binding CA9 and the antibody or antibody fragment that binds to ENPP3 is a means for binding ENPP3. In some embodiments, the administering comprises administering a lymphocyte such as a T cell, NK cell, or NKT cell comprising the CAR construct comprising the first expression construct and the second expression construct. In some embodiments, the CAR construct comprises a first fusion protein comprising the first antibody or antibody fragment that binds to CA9 connected to a first signaling domain, optionally via one or more linkers and a first transmembrane domain. In some embodiments, the first signaling domain comprises SLP76. In some embodiments, the SLP76 peptide comprises SEQ ID NO:WSGR Docket Number: 63580-708.6012712, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 2712. In some embodiments, the SLP76 peptide consists or consists essentially of SEQ ID NO: 2712. In some embodiments, the CAR construct comprises a second fusion protein comprising the second antibody or antibody fragment that binds to ENPP3 connected to a second signaling domain, optionally via one or more linkers and a second transmembrane domain. In some embodiments, the second signaling domain comprises LAT. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 3009. In some embodiments, the LAT peptide consists or consists essentially of SEQ ID NO: 3009. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, and does not comprise amino acids 1-63 of SEQ ID NO: 2723 or amino acids 173-235 of SEQ ID NO: 2723. The first and the second fusion protein may independently have a formula disclosed herein.

[0041] Various embodiments of the present disclosure provide LAT signaling domains that improve potency of a T cell therapy. Additional embodiments provide CAR constructs comprising a LAT signaling domain, where expression of the CAR is improved as compared to a CAR construct comprising a native LAT signaling domain (e.g., SEQ ID NO: 2715). Nonlimiting example LAT signaling domains provided herein include those having SEQ ID NOS: 2714, 2723, 2724, 3007-3014. The LAT signaling domains may consist of any one of SEQ ID NOS: 2714, 2723, 2724, 3007-3014. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 3009. In some embodiments, the LAT peptide consists or consists essentially of SEQ ID NO: 3009. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, and does not comprise amino acids 1-63 of SEQ ID NO: 2723 or amino acids 173-235 of SEQ ID NO: 2723.

[0042] Also provided herein are fusion proteins (e.g., CAR constructs) comprising a LAT signaling domain, such as a LAT signaling domain of any one of SEQ ID NOS: 2714, 2723, 2724, 3007-3014. Provided herein are fusion proteins (e.g., CAR constructs) comprising a LAT signaling domain, such as a LAT signaling domain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of SEQ ID NOS: 2714, 2723, 2724, 3007-3014. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 3009. In some embodiments, the LAT peptide consists or consists essentially of SEQ ID NO: 3009. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, and does not comprise amino acids 1-63 of SEQ ID NO: 2723 or amino acids 173-235 of SEQ ID NO: 2723. Also provided are SH2-domain-containing leukocyte protein of 76 kDa (SLP76) fusion proteins (e.g., CAR constructs) comprising a SLP76 signaling domain. Provided herein are fusion proteins (e.g., CAR constructs) comprising a SLP76 signaling domain, such as a SLP76 signaling domainWSGR Docket Number: 63580-708.601 having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of SEQ ID NOS: 2712 or 2713. Non-limiting example fusion proteins include those having Formula I or Formula II. The fusion proteins may have Formula la, Formula lb, Formula Ic, Formula Id, Formula le, Formula If, Formula Ig, Formula Ih, Formula li, Formula Ij, Formula Ik, Formula II, Formula Im, Formula In, Formula Io, Formula Ip, or Formula Iq. The fusion proteins may have Formula Ila, Formula lib, Formula lie, Formula lid, Formula lie, Formula Ilf, Formula Ilg, Formula Ilh, Formula Hi, Formula Ilj, Formula Ilk, Formula III, Formula Ilm, Formula UN, Formula IIo, Formula Up, or Formula Ilq. The fusion proteins may have Formula XXXI, Formula XXXIa, Formula XXXIb, Formula XXXIc, Formula XXXId, Formula XXXII, Formula XXXIIa, Formula XXXIIb, Formula XXXIIc, or Formula XXXIId. The fusion proteins may have Formula XXXIIa, Formula XXXIIal, Formula XXXIIa2, Formula XXXIIa3, Formula XXXIIa4, Formula XXXIIa5, Formula XXXIIa6, Formula XXXIIa7, or Formula XXXIIa8. The fusion proteins may have Formula XXXIIb, Formula XXXIIbl, Formula XXXIIb2, Formula XXXIIb3, Formula XXXIIb4, Formula XXXIIb5, Formula XXXIIb6, Formula XXXIIb7, or Formula XXXIIb8. The fusion proteins may have Formula XXXIIc, Formula XXXIIcl, Formula XXXIIc2, Formula XXXIIc3, Formula XXXIIc4, Formula XXXIIc5, Formula XXXIIc6, Formula XXXIIc7, or Formula XXXIIc8. The fusion proteins may have Formula XXXIId, Formula XXXIIdl, Formula XXXIId2, Formula XXXIId3, Formula XXXIId4, Formula XXXIId5, Formula XXXIId6, Formula XXXIId7, or Formula XXXIId8. As a non-limiting example, a LAT fusion protein has a formula selected from Formulas II, XXXII, XXXIIa3, XXXIIb3, and XXXIIc3. As a non -limiting example, a SLP76 fusion protein has a formula selected from Formulas la-Ii, In-Iq, XXXI, XXXIa, XXXIb, and XXXId.

[0043] Also provided herein are methods of T cell therapy comprising administering to a subject in need thereof a T cell comprising a LAT signaling domain, e.g., a LAT signaling domain of any one of SEQ ID NOS: 2714, 2723, 2724, 3007-3014. The LAT signaling domain may comprise a LAT signaling domain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of SEQ ID NOS: 2714, 2723, 2724, 3007-3014. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, or a sequence having 1, 2, 3, 4, or 5 amino acids different than SEQ ID NO: 3009. In some embodiments, the LAT peptide consists or consists essentially of SEQ ID NO: 3009. In some embodiments, the LAT peptide comprises SEQ ID NO: 3009, and does not comprise amino acids 1-63 of SEQ ID NO: 2723 or amino acids 173-235 of SEQ ID NO: 2723. The LAT signaling domain may be part of a first fusion protein (e.g., first CAR construct). The T cell may further comprise a SLP76 signaling domain, e.g., a SLP76 signaling domain of SEQ ID NO:WSGR Docket Number: 63580-708.6012712 or 2713. The SLP76 signaling domain may comprise a SLP76 signaling domain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any one of SEQ ID NOS: 2712 or 2713. The SLP76 signaling domain may be part of a second fusion protein (e.g., a second CAR construct). In some embodiments, the first fusion protein comprises the LAT signaling domain connected to a first antibody or antibody fragment thereof that binds to a first target of a first cell, optionally via one or more linkers and / or a first transmembrane domain. In some embodiments, the second fusion protein comprises the SLP76 signaling domain connected to a second antibody or antibody fragment thereof that binds to a second target of a second cell, optionally via one or more linkers and / or a first transmembrane domain. For increased cell selectivity, the first cell and the second cell may be the same cell. Methods of T cell therapy include methods for treating cancer, e.g., where the cancer cell expresses the first target and / or the second target. As such, the method may comprise killing a cancer cell comprising the first target and the second target. The method may also comprise inhibiting proliferation of a cancer cell comprising the first target and the second target. Nonlimiting example fusion proteins for methods herein include those having Formula I or Formula ll. The fusion proteins may have Formula la, Formula lb, Formula Ic, Formula Id, Formula le, Formula If, Formula Ig, Formula Ih, Formula li, Formula Ij, Formula Ik, Formula II, Formula lm, Formula IN, Formula Io, Formula Ip, or Formula Iq. The fusion proteins may have Formula Ila, Formula lib, Formula lie, Formula lid, Formula lie, Formula Ilf, Formula Ilg, Formula Ilh, Formula Hi, Formula Ilj, Formula Ilk, Formula III, Formula Ilm, Formula UN, Formula IIo, Formula Up, or Formula Ilq. The fusion proteins may have Formula XXXI, Formula XXXIa, Formula XXXIb, Formula XXXIc, Formula XXXId, Formula XXXII, Formula XXXIIa, Formula XXXIIb, Formula XXXIIc, or Formula XXXIId. The fusion proteins may have Formula XXXIIa, Formula XXXIIal, Formula XXXIIa2, Formula XXXIIa3, Formula XXXIIa4, Formula XXXIIa5, Formula XXXIIa6, Formula XXXIIa7, or Formula XXXIIa8. The fusion proteins may have Formula XXXIIb, Formula XXXIIbl, Formula XXXIIb2, Formula XXXIIb3, Formula XXXIIb4, Formula XXXIIb5, Formula XXXIIb6, Formula XXXIIb7, or Formula XXXIIb8. The fusion proteins may have Formula XXXIIc, Formula XXXIIcl, Formula XXXIIc2, Formula XXXIIc3, Formula XXXIIc4, Formula XXXIIc5, Formula XXXIIc6, Formula XXXIIc7, or Formula XXXIIc8. The fusion proteins may have Formula XXXIId, Formula XXXIId 1, Formula XXXIId2, Formula XXXIId3, Formula XXXIId4, Formula XXXIId5, Formula XXXIId6, Formula XXXIId7, or Formula XXXIId8. As a nonlimiting example, a LAT fusion protein has a formula selected from Formulas II, XXXII, XXXIIa3, XXXIIb3, and XXXIIc3. As a non-limiting example, a SLP76 fusion protein has a formula selected from Formulas la-Ii, In-Iq, XXXI, XXXIa, XXXIb, and XXXId.WSGR Docket Number: 63580-708.601BRIEF DESCRIPTION OF THE DRAWINGS

[0044] FIG. 1 is an example, non-limiting embodiment of a CAR T cell comprising a first construct comprising an antigen-binding domain specific for CA9, and another antigen-binding domain specific for ENPP3.

[0045] FIG. 2A illustrates expression of CA9 VHH binding domain constructs as measured by flow cytometry.

[0046] FIG. 2B illustrates expression of ENPP3 VHH binding domain constructs as measured by flow cytometry.

[0047] FIG. 3 illustrates efficacy of CA9 VHH binding domain constructs in 7860 CA9+ENPP3+ cells.

[0048] FIG. 4 illustrates efficacy of CA9 VHH binding domain constructs in ACHN CA9+ENPP3+ cells.

[0049] FIG. 5 illustrates efficacy of CA9 VHH binding domain constructs in 7860 CA9+ENPP3+ cells.

[0050] FIG. 6 illustrates efficacy of CA9 VHH binding domain constructs in ACHN CA9+ENPP3+ cells.

[0051] FIG. 7 illustrates efficacy of ENPP3 VHHxCA9 binding domain constructs in 7860 CA9+ENPP3+ cells.

[0052] FIG. 8 illustrates efficacy of ENPP3 VHHxCA9 binding domain constructs in ACHN CA9+ENPP3+ cells.

[0053] FIG. 9 illustrates efficacy of ENPP3 VHHxCA9 binding domain constructs in A704 CA9+ ENPP31ow cells.

[0054] FIG. 10 illustrates efficacy of CA9xENNP3 binding domain constructs in ACHN CA9+ENPP3+ cells.

[0055] FIG. 11 illustrates efficacy of CA9xENNP3 binding domain constructs in A704 CA9+ENPP3+ cells.

[0056] FIG. 12 illustrates efficacy of CA9xENNP3 binding domain constructs in 7860 CA9+ENPP3+ cells.

[0057] FIG. 13 illustrates anti-CA9 activity of CA9 VHH binding domain constructs in ACHN CA9+ENPP3KO cells.

[0058] FIG. 14 illustrates anti-ENPP3 activity of CA9 VHH binding domain constructs in ACHN CA9KO ENPP3+ cells.

[0059] FIG. 15 illustrates anti-CA9 activity of CA9 VHH binding domain constructs in ACHN CA9+ENPP3KO cells.WSGR Docket Number: 63580-708.601

[0060] FIG. 16 illustrates anti-ENPP3 activity of CA9 VHH binding domain constructs in ACHN CA9KO ENPP3+ cells.

[0061] FIG. 17 illustrates efficacy of ENPP3 VHHxCA9 binding domain constructs in A704 CA9+ ENPP3 KO cells.

[0062] FIG. 18 illustrates efficacy of ENPP3 VHHxCA9 binding domain constructs in ACHN CA9 KO ENPP3+ cells.

[0063] FIG. 19 illustrates efficacy of ENPP3 VHH binding domain constructs in combination with a CA9 binding domain construct in A704 CA9KOENPP31ow cells.

[0064] FIG. 20 illustrates anti-CA9 activity of CA9xENNP3 binding domain constructs in ACHN CA9+ENPP3KO cells.

[0065] FIG. 21 illustrates anti-ENPP3 activity of CA9xENNP3 binding domain constructs in ACHN CA9KO ENPP3+ cells.

[0066] FIG. 22 illustrates anti-ENNP3 activity of CA9xENNP3 binding domain constructs in A704 CA9KO ENPP3+ cells.

[0067] FIG. 23 illustrates an experimental protocol for treating mice with CA9xENNP3 binding domain constructs.

[0068] FIGs. 24-25 illustrate flux of ACHN CA9+ENPP3+ tumors following treatment with CA9xENNP3 binding domain constructs.

[0069] FIG. 26 illustrates an experimental schematic for administration of CA9, ENPP3, and CA9xENPP3 constructs to mice xenografted with CA9KOENPP3+ and CA9+ENPP3+ cells.

[0070] FIG. 27 illustrates tumor volume of CA9KOENPP3+ and CA9+ENPP3+ tumors following treatment with CA9xENNP3 binding domain constructs.

[0071] FIG. 28 illustrates tumor volume of CA9KOENPP3+ tumors following treatment with CA9xENPP3 constructs.

[0072] FIG. 29 illustrates tumor volume of CA9+ENPP3+ tumors following treatment with CA9xENPP3 constructs.

[0073] FIGs. 30A, 30B, 31A, and 31B illustrate tumor volume of CA9+ENPP3+ and CA9KOENPP3+ tumors following treatment with CA9xENPP3 constructs.

[0074] FIG. 32 illustrates ENPP3 expression of humanized ENPP3 VHH binding domain constructs as measured by flow cytometry.

[0075] FIG. 33 illustrates cytotoxicity of humanized ENPP3 VHH binding domains in ACHN and A704 cells over time.

[0076] FIG. 34 illustrates expression of CA9 and ENPP3 in histological clear cell renal cell carcinoma samples.WSGR Docket Number: 63580-708.601

[0077] FIG. 35 illustrates efficacy of a CA9xENPP3 construct in clear cell renal cell carcinoma cell lines with varying amounts of CA9 and ENPP3.

[0078] FIG. 36 illustrates cytotoxicity of a CA9xENPP3 construct in clear cell renal cell carcinoma cell lines with CA9 and ENPP3 knockout.

[0079] FIG. 37 illustrates TNFa and IL-2 release following treatment with a CA9xENPP3 construct in clear cell renal cell carcinoma cells.

[0080] FIG. 38 illustrates tumor volume following treatment with a CA9xENPP3 construct in mice xenografted with CA9KOENPP3+ and CA9+ENPP3+ cells.

[0081] FIG. 39 illustrates tumor volume of CA9+ENPP3+ and CA9+ENPP3KOcells following treatment with a CA9xENPP3 construct.

[0082] FIG. 40 illustrates flux of clear cell renal cell carcinoma tumors following treatment with a CA9xENPP3 construct.

[0083] FIG. 41 illustrates tumor volume of CA9+ENPP3+ tumors and alanine transaminase levels in mice treated with a CA9xENPP3 construct.

[0084] FIG. 42 illustrates in vitro activity against CA9+ENPP3+ tumor cells, where CA9, SLP76 x ENPP3, LAT constructs mediated significant lysis of CA9+ENPP3+ tumor cells (7860 CA9139K ENPP3132K) in short-term killing assays and attained tumor growth inhibition (TGI) comparable to single-targeting 1st and 2nd generation CAR constructs.

[0085] FIG. 43 illustrates that CA9, SLP76 x ENPP3, LAT constructs maintained persistent cytotoxicity against CA9+ENPP3+ tumor cells (7860 cells) following repeated tumor cell rechallenge.

[0086] FIG. 44 illustrates that CA9, SLP76 x ENPP3, LAT constructs maintained persistent cytotoxicity against CA9+ENPP3+ tumor cells (ACHN cells) following repeated tumor cell rechallenge.

[0087] FIG. 45 illustrates that CA9, SLP76 x ENPP3, LAT constructs maintained persistent cytotoxicity against CA9+ENPP3+ tumor cells (7860 cells) following repeated tumor cell rechallenge.

[0088] FIG. 46 illustrates coculturing of CA9, SLP x ENPP3, LAT constructs with CA9+ENPP3+ tumor cells (7860 CA950K ENPP335K) induced potent secretion of effector cytokines.

[0089] FIG. 47 illustrates anti -turn or activity of CA9, SLP x ENPP3, LAT constructs, as compared to an ENPP3 2nd generation CAR construct and a CA9 2nd generation CAR construct.WSGR Docket Number: 63580-708.601

[0090] FIG. 48 illustrates that CA9 single-positive target cells (7860 CA9500K ENPP3KO) were eliminated by the CA9 2nd generation and the CA9 1st generation CAR constructs, but were spared by CA9, SLP x ENPP3, LAT constructs.

[0091] FIG. 49 illustrates that ENPP3 single-positive target cells (7860 CA9K0 ENPP350K) were eliminated by the ENPP3 2nd generation CAR construct, but were spared by CA9, SLP x ENPP3.

[0092] FIG. 50 illustrates that coculture with ENPP3 single-positive target cells (7860 CA9K0 ENPP350K) do not induce the secretion of effector cytokines by CA9, SLP x ENPP3, LAT constructs.DETAILED DESCRIPTION

[0093] Treatment of solid tumor malignancies with CAR T cells may be limited by off-target toxicity due to low expression of target antigens on healthy cells. Provided herein are CAR T cells that may address such toxicity by binding to two target antigens of tumor cells. The CAR T cells may comprise a first fusion protein (e.g., first CAR construct) that binds to the first antigen, and a second fusion protein (e.g., second CAR construct) that binds to the second antigen. The first fusion protein may comprise a first signaling molecule, LAT, and the second fusion protein may comprise a second signaling molecule, SLP76. Certain LAT molecules provided herein may increase potency of CAR T cell therapy, while maintaining selectivity for cells expressing both target antigens. Certain LAT molecules provided herein may increase expression of CAR constructs as compared to CAR constructs having wild-type LAT molecules. Certain CAR T cells herein bind to CA9 and / or ENPP3.

[0094] CA9, also known as carbonic anhydrase IX (CAIX), is a protein that belongs to the carbonic anhydrase family. Carbonic anhydrases are zinc metalloenzymes that catalyze the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid. They participate in a variety of biological processes, including maintaining the acid-base balance and transporting carbon dioxide. CA9 is mainly expressed in the gastrointestinal tract and facilitates acid secretion. However, CA9 can be overexpressed in cancers such as clear cell renal cell carcinoma (ccRCC), as well as some other cancer types. The sequence of CA9 is provided in Table 1.

[0095] ENPP3, also known as ectonucleotide pyrophosphatase / phosphodiesterase family member 3 and CD203c, is a protein that belongs to the cell-surface ectonucleotide pyrophosphatase / phosphodiesterase family. ENPP3 is a single pass transmembrane protein that functions to metabolize extracellular nucleotides, such as ATP, GTP, UTP, and CTP. ENPP3 is made up of three domains, a nuclease-like domain (NUC), a phosphodiesterase catalytic domain (PDE), and a somatomedin B-like (SMB) domain. However, ENPP3 can be overexpressed inWSGR Docket Number: 63580-708.601 cancers such as clear cell renal cell carcinoma (ccRCC), as well as some other cancer types. The sequence of ENPP3 is provided in Table 1.Table 1

[0096] Treatment of solid tumor malignancies with cell therapy approaches (CAR T cells) is often limited by target expression - an ideal target for conventional CAR T cells would be expression on the tumor tissue, and no or low expression on healthy tissues. Otherwise, there will be off-tumor on-target toxicity due to CAR T cell cytotoxicity of normal tissue. This has been shown previously with targeting of CA9 in clear cell renal cell carcinoma (ccRCC) where though efficacious against tumor, on-target toxicities were identified due to CA9 expression in other tissues, such as bile ducts, leading to the conclusion of the trial. Provided herein are CARWSGR Docket Number: 63580-708.601T cells that may address this issue by having two antigen-binding domains - one specific for CA9, and another specific for ENPP3. A non-limiting example is shown in FIG. 1. As such, CA9 may be de-risked as a target for CAR T cells through the identification and exploitation of a second target antigen, such as ENPP3, in ccRCC. ENPP3 displays high tumor-specific expression, with a different subset of healthy tissue liabilities including basophils and intestinal crypts. Combined, co-expression of CA9 and ENPP3 may be limited to CA9+, ENPP3+expressing tumors, such as ccRCC.CA9-binding antibodies and antibody fragments

[0097] Provided herein are antibodies and antibody fragments that bind CA9. Moreover, in certain instances, the antibodies and antibody fragments provided herein are also advantageous in that they target cell expressing CA9, e.g., cancer cells overexpressing CA9. As an example, clear cell renal cell carcinoma. In certain embodiments, the antibody and antibody fragment is a single-chain antibody. In certain embodiments, the single-chain antibody is a single chain variable fragment (scFv).

[0098] Antibody is used in the broadest sense and generally refers to and / or includes monoclonal antibodies, multi-valent antibodies, multi-specific, single domain antibodies, and antigen-binding fragments of antibodies that bind CA9. Antibody fragments (also referred to as: antigen-binding antibody fragments or antigen-binding fragments) generally refer to and include antibody-derived proteins that comprise a functional set of CDRs (e.g., a CDRH1-3 and CDRL1-3 or a CDRH1-3 for a single domain antibody) that bind CA9, and have a molecular weight less than a full length IgG antibody (e.g., a molecular weight less than -150,00 Daltons). In certain embodiments, an antibody fragment (e.g., CA9-binding fragment) includes: fragment antigen binding (Fab) fragments, F(ab’)2 fragments, Fab’ fragments, Fv fragments, IgG (rlgG) fragments, a VH domain paired / complexed with a VL domain, and single chain antibody fragments, including single chain variable fragments (sFv or scFv). Single domain antibodies generally refer to an antibody having a single variable region that confers binding to a target protein, utilizing functional set of CDRs comprising a CDR1, CDR2, and CDR3. In certain instances for single domain antibodies, CDR1, CDR2, and CDR3 and CDRH1, CDRH2, and CDRH3 are used interchangeably. In certain embodiments, a single domain antibody is a VHH or comprises a VHH domain.

[0099] Antibodies and antigen-binding fragments of antibodies also include genetically engineered, and / or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multi-specific antibodies, multi-valent antibodies, diabodies, triabodies, and tetrabodies, tandem di-scFv, tandem tri-scFv. Antibodies also include full-lengthWSGR Docket Number: 63580-708.601 antibodies (also referred to as: an intact antibody and / or whole antibody) and also includes antibodies having a structure substantially similar to native antibodies, such as those having heavy chains that contain a CHI domain and an Fc region. Such Fc regions can be of any class or sub-class, including IgG and sub-classes thereof (e.g., IgGl and IgG4), IgM, IgE, IgA, and IgD.

[0100] CA9 generally refers to and / or includes the protein encoded by the CA9 gene. CA9 is generally known as carbonic anhydrase 9, membrane antigen MN, P54 / 58N, renal cell carcinoma-associated antigen G250 (RCC-associated antigen G250), and pMWl. In certain embodiments, the CA9 gene refers to NCBI GenelD 768 and / or HGNC ID: HGNC: 1383, which includes sequence information on CA9. In certain embodiments, a CA9 protein refers to and includes the protein(s) of UniProt ID: QI 6790. In certain instances, CA9 comprises a protein comprising the amino acid sequence of SEQ ID NO: 2710.

[0101] Antibodies and / or antibody fragments described and exemplified herein bind CA9. Binding can be determined by bio-layer interferometry, surface plasmon resonance, isothermal titration calorimetry, and / or ELISA. Affinity generally refers to and / or includes the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody or antibody fragment) and its binding target (e.g., CA9). Affinity (i.e., the strength of binding interactions) can also be determined by any known method, such as by bio-layer interferometry, surface plasmon resonance, isothermal titration calorimetry, and / or ELISA. In certain embodiments, binding to CA9 can be determined by binding to recombinant CA9, e.g., a CA9 molecule having any one or any fragment of the amino acid sequences of Table 1. For example, Example 1 shows how binding can be determined for antibodies and antibody fragments that bind CA9. In some embodiments, the antibody or antibody fragment binds the CA9 with an affinity of less than about 1 micromolar (pM).

[0102] Complementarity determining regions (CDRs) generally comprise the amino acids within antibody variable regions that confer antigen specificity and / or binding affinity (e.g., to CA9). In general, there are three CDRs in each heavy chain variable region (CDRH1, CDRH2, or CDRH3) and three CDRs in each light chain variable region (CDRL1, CDRL2, or CDRL3). Framework regions (FRs) generally refer to and / or include non-CDR regions of the heavy and light chain variable regions. In general, there are four FRs in each full-length heavy chain variable region (FRH1, FRH2, FRH3, and FRH4), and four FRs in each full-length light chain variable region (FRL1, FRL2, FRL3, and FRL4).

[0103] Variable regions (also referred to as variable domains) generally refer to and include the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen (e.g., a single variable domain comprises a CDR 1, CDR 2, or CDR 3). The variable domains ofWSGR Docket Number: 63580-708.601 the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three CDRs. In certain instances, a single VH or VL domain can be sufficient to confer antigenbinding specificity (e.g., binding to CA9).

[0104] Provided and exemplified herein are antibodies and antibody fragments that bind CA9, wherein the antibodies and / or antibody fragments comprise: (i) a light chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VL selected from any one of the antibody clones in Table 2, (ii) a heavy chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VH selected from any one of the antibody clones in Table 2, and (iii) a linker, wherein the VH and VL are selected from the same antibody and antibody fragment clone in Table 2.Table 2WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0105] Provided and exemplified herein are antibodies and antibody fragments that bind CA9, wherein the antibodies and / or antibody fragments comprise: (i) a light chain variable domainWSGR Docket Number: 63580-708.601 comprising: a light chain complementarity determining region 1 (CDRL1; a light chain complementarity determining region 2 (CDRL2); and a light chain complementarity determining region 3 (CDRL3); (ii) a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1); a heavy chain complementarity determining region 2 (CDRH2); and a heavy chain complementarity determining region 3 (CDRH3). Such antibodies are provided in Table 3.Table 3WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0106] In certain embodiments, the antibody or antibody fragment that binds CA9 comprises (i) a light chain variable domain comprising the CDRL1-3 amino acid sequence selected from any one of the antibody clones in Table 3, and (ii) a heavy chain variable domain comprising a CDRH1-3 amino acid sequence selected from any one of the antibody clones in Table 3, wherein the CDRH1-3 and CDRL1-3 are selected from the same antibody clone in Table 3.

[0107] In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 5, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 6, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 4. In certainWSGR Docket Number: 63580-708.601 embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 8, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 7. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 12, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 10. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 14, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 17, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 18, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 16. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 20, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 21, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 19. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 23, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 24, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 22. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 26, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 27, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 29, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 28. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 32, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 33, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 31. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 35, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 36, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 34. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 38, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 39, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 37. In certainWSGR Docket Number: 63580-708.601 embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 41, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 40. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 45, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 43. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 47, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 48, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 50, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 51, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 49. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 53, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 54, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 52. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 56, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%,WSGR Docket Number: 63580-708.60197%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 57, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 55. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 59, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 60, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 58. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 62, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 63, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 61. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 65, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 66, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 64. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 68, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 69, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 67. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 71, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 72, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 70. InWSGR Docket Number: 63580-708.601 certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 74, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 75, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 73. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 77, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 78, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 76.

[0108] In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 79-81, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 82-84. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 85-87, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 88-90. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 91-93, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 94-96. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 97-99, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 100-102. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 103-105, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 106-108. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 109-111, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 112-114. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 115-117, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 118-120. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 121-123, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 124-126. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 127-129, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 130-132. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 133-135, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 136-138. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 139-141, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS:WSGR Docket Number: 63580-708.601142-144. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 145-147, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 148-150. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 151-153, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 154-156. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 157-159, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 160-162. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 163-165, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 166-168. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 169-171, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 172-174. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 175-177, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 178-180. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 181-183, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 184-186. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 187-189, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 190-192. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 193-195, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 196-198. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 199-201, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 202-204. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 205-207, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 208-210. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 211-213, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 214-216. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 217-219, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 220-222. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 223-225, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 226-228. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 229-231, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 232-234.

[0109] Provided and exemplified herein are antibodies and antibody fragments that bind CA9, wherein the antibodies and / or antibody fragments comprise: (i) a light chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VL selected from anyWSGR Docket Number: 63580-708.601 one of the antibody clones in Table 4, (ii) a heavy chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VH selected from any one of the antibody clones in Table 4, and (iii) a linker, wherein the VH and VL are selected from the same antibody and antibody fragment clone in Table 4.Table 4WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0110] Provided and exemplified herein are antibodies and antibody fragments that bind CA9, wherein the antibodies and / or antibody fragments comprise: (i) a light chain variable domainWSGR Docket Number: 63580-708.601 comprising: a light chain complementarity determining region 1 (CDRL1; a light chain complementarity determining region 2 (CDRL2); and a light chain complementarity determining region 3 (CDRL3); (ii) a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1); a heavy chain complementarity determining region 2 (CDRH2); and a heavy chain complementarity determining region 3 (CDRH3). Such antibodies are provided in Table 5.Table 5WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601[OHl] In certain embodiments, the antibody or antibody fragment that binds CA9 comprises (i) a light chain variable domain comprising the CDRL1-3 amino acid sequence selected from any one of the antibody clones in Table 5, and (ii) a heavy chain variable domain comprising a CDRH1-3 amino acid sequence selected from any one of the antibody clones in Table 5, wherein the CDRH1-3 and CDRL1-3 are selected from the same antibody clone in Table 5.

[0112] In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 236, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 237, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 235. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 239, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 240, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 238. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 242, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 243, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 241. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%,WSGR Docket Number: 63580-708.60196%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 245, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 246, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 244. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 248, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 249, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 247. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 251, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 252, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 250. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 254, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 255, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 253. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 257, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 258, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 256. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 260, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 261, and a linker. In some embodiments, the antibody or antibody fragmentWSGR Docket Number: 63580-708.601 comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 259. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 263, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 264, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 262. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 266, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 267, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 265. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 269, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 270, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 268. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 272, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 273, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 271. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 275, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 276, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 274. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at leastWSGR Docket Number: 63580-708.60180%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 278, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 279, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 277. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 281, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 282, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 280. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 284, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 285, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 283. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 287, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 288, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 286. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 290, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 291, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 289. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 293, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 294, and a linker. In someWSGR Docket Number: 63580-708.601 embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 292. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 296, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 297, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 295. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 299, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 300, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 298. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 302, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 303, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 301.

[0113] In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 304-306, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 307-309. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 310-312, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 313-315. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 316-318, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 319-321. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 322-324, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 325-327. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 328-330, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 331-333. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 334-336, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 337-339. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQWSGR Docket Number: 63580-708.601ID NOS: 340-342, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 343-345. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 346-348, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 349-351. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 352-354, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 355-357. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 358-360, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 361-363. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 364-366, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 367-369. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 370-372, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 373-375. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 376-378, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 379-381. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 382-384, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 385-387. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 388-390, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 391-393. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 394-396, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 397-399. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 400-402, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 403-405. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 406-408, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 409-411. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 412-414, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 415-417. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 418-420, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 421-423. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 424-426, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 427-429. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 430-432, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 433-435. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 436-438, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 439-441.WSGR Docket Number: 63580-708.601

[0114] Provided and exemplified herein are antibodies and antibody fragments that bind CA9, wherein the antibodies and / or antibody fragments comprise: a heavy chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VH selected from any one of the antibody clones in Table 6. In some embodiments, the CA9 antibody or antibody fragment comprises: a heavy chain variable domain having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583.Table 6WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0115] Provided and exemplified herein are single domain antibodies and antibody fragments that bind CA9, wherein the single domain antibodies and / or antibody fragments comprise: (i) a heavy chain variable region comprising: a heavy chain complementarity determining region 1 (CDRH1); a heavy chain complementarity determining region 2 (CDRH2); and a heavy chain complementarity determining region 3 (CDRH3). Such antibodies are provided in Table 7.Table 7WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0116] In certain embodiments, the antibody or antibody fragment that binds CA9 comprises a heavy chain variable domain comprising a CDRH1-3 amino acid sequence selected from anyWSGR Docket Number: 63580-708.601 one of the antibody clones in Table 7. In some embodiments, the CA9 antibody or antibody fragment comprises: (i) a heavy chain variable region comprising: a heavy chain complementarity determining region 1 (CDRH1) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1044; a heavy chain complementarity determining region 2 (CDRH2) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1045; and a heavy chain complementarity determining region 3 (CDRH3) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1046. In some embodiments, the CA9 antibody or antibody fragment comprises: (i) a heavy chain variable region comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising SEQ ID NO: 1044; a heavy chain complementarity determining region 2 (CDRH2) comprising SEQ ID NO: 1045; and a heavy chain complementarity determining region 3 (CDRH3) comprising SEQ ID NO: 1046.

[0117] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 442. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 443. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 444. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 445. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 446. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 447. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 448. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 449. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 450. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 451. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 452. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 453. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 454. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 455. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 456. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 457. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 458. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 459. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 460. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 461. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 462. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 463. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 464. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 465. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 466. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 467. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 468. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 469. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 470. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 471. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 472. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 473. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 474. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 475. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 476. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 477. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 478. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 479. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 480. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 481. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 482. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 483. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 484. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 485. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 486. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 487. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 488. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 489. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 490. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 491. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 492. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 493. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 494. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 495. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 496. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 497. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 498. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 499. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 500. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 501. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 502. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 503. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 504. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 505. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 506. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 507. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 508. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 509. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 510. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 511. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 512. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 513. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 514. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 515. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 516. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 517. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 518. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 519. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 520. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 521. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 522. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 523. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 524. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 525. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 526. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 527. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 528. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 529. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 530. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 531. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 532. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 533. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 534. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 535. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 536. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 537. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 538. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 539. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 540. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 541. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 542. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 543. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 544. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 545. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 546. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 547. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 548. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 549. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 550. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 551. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 552. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 553. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 554. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 555. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 556. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 557. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 558. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 559. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 560. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 561. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 562. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 563. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 564. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 565. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 566. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 567. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 568. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 569. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 570. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 571. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 572. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 573. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 574. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 575. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 576. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 577. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 578. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 579. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 580. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 581. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 582. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 583. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 584. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 585. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 586. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 587. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 588. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 589. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 590. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 591. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 592. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 593. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 594. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 595. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 596. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 597. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 598. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 599. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 600. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 601. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 602. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 603. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 604. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 605. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 606. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 607. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 608. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 609. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 610. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 611. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 612. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 613. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 614. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 615. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 616. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 617. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 618. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 619. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 620.

[0118] In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 621-623. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 624-626. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 627-629. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 630-632. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 633-635. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 636-638. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 639- 641. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 642-644. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 645-647. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 648-650. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 651-653. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 654-656. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 657-659. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 660- 662. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 663-665. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 666-668. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 669-671. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 672-674. In some embodiments, the variable domain of the single domainWSGR Docket Number: 63580-708.601 antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 675-677. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 678-680. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 681- 683. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 684-686. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 687-689. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 690-692. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 693-695. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 696-698. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 699-701. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 702- 704. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 705-707. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 708-710. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 711-713. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 714-716. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 717-719. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 720-722. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 723- 725. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 726-728. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 729-731. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 732-734. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 735-737. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 738-740. In some embodiments, the variable domain of the single domain antibody or antibody fragmentWSGR Docket Number: 63580-708.601 comprises the CDR1-3 of SEQ ID NOS: 741-743. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 744- 746. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 747-749. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 750-752. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 753-755. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 756-758. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 759-761. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 762-764. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 765- 767. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 768-770. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 771-773. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 774-776. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 777-779. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 780-782. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 783-785. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 786- 788. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 789-791. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 792-794. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 795-797. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 798-800. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 801-803. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 804-806. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 807-WSGR Docket Number: 63580-708.601809. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 810-812. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 813-815. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 816-818. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 819-821. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 822-824. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 825-827. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 828- 830. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 831-833. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 834-836. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 837-839. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 840-842. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 843-845. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 846-848. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 849- 851. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 852-854. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 855-857. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 858-860. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 861-863. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 864-866. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 867-869. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 870- 872. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 873-875. In some embodiments, the variableWSGR Docket Number: 63580-708.601 domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 876-878. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 879-881. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 882-884. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 885-887. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 888-890. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 891- 893. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 894-896. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 897-899. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 900-902. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 903-905. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 906-908. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 909-911. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 912- 914. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 915-917. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 918-920. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 921-923. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 924-926. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 927-929. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 930-932. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 933- 935. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 936-938. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 939-941. In some embodiments, the variable domain of the single domain antibody orWSGR Docket Number: 63580-708.601 antibody fragment comprises the CDR1-3 of SEQ ID NOS: 942-944. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 945-947. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 948-950. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 951-953. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 954- 956. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 957-959. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 960-962. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 963-965. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 966-968. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 969-971. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 972-974. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 975- 977. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 978-980. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 981-983. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 984-986. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 987-989. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 990-992. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 993-995. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 996- 998. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 999-1001. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1002-1004. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1005-1007. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3WSGR Docket Number: 63580-708.601 of SEQ ID NOS: 1008-1010. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1011-1013. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1014-1016. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1017-1019. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1020-1022. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1023-1025. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1026-1028. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1029-1031. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1032-1034. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1035-1037. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1038-1040. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1041-1043. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1044-1046. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1047-1049. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1050-1052. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1053-1055. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1056-1058. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1059-1061. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1062-1064. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1065-1067. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1068-1070. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1071-1073. In some embodiments, the variable domain of the single domain antibody or antibody fragmentWSGR Docket Number: 63580-708.601 comprises the CDR1-3 of SEQ ID NOS: 1074-1076. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1077-1079. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1080-1082. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1083-1085. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1086-1088. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1089-1091. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1092-1094. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1095-1097. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1098-1100. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1101-1103. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1104-1106. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1107-1109. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1110-1112. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1113-1115. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1116-1118. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1119-1121. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1122-1124. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1125-1127. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1128-1130. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1131-1133. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1134-1136. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1137-1139. In some embodiments, the variable domain of the single domain antibody orWSGR Docket Number: 63580-708.601 antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1140-1142. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1143-1145. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1146-1148. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1149-1151. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1152-1154. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1155-1157.

[0119] Provided and exemplified herein are antibodies and antibody fragments that bind CA9, wherein the antibodies and / or antibody fragments comprise: a heavy chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VH selected from any one of the antibody clones in Table 8. In some embodiments, the CA9 antibody or antibody fragment comprises: a heavy chain variable domain having at least 80%, 85%, 90%, 91%, 92%,93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168.Table 8WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0120] Provided and exemplified herein are antibodies and antibody fragments that bind CA9, wherein the antibodies and / or antibody fragments comprise: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1); a heavy chainWSGR Docket Number: 63580-708.601 complementarity determining region 2 (CDRH2); and a heavy chain complementarity determining region 3 (CDRH3). Such antibodies are provided in Table 9.Table 9WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0121] In certain embodiments, the antibody or antibody fragment that binds CA9 comprises a heavy chain variable domain comprising a CDRH1-3 amino acid sequence selected from any one of the antibody clones in Table 9.

[0122] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1158. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1159. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1160. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1161. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1162. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ IDWSGR Docket Number: 63580-708.601NO: 1163. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1164. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1165. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1166. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1167. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1169. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1170. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1171. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1172. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1173. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1174. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1175. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1176. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ IDWSGR Docket Number: 63580-708.601NO: 1177. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1178. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1179. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1180. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1181. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1182. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1183. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1184. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1185. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1186. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1187. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1188. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1189. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1190. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ IDWSGR Docket Number: 63580-708.601NO: 1191. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1192. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1193. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1194. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1195. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1196. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1197. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1198. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1199. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1200. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1201. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1202. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1203. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1204. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ IDWSGR Docket Number: 63580-708.601NO: 1205. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1206. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1207. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1208. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1209. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1210.

[0123] In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1211-1213. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1214-1216. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1217-1219. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1220-1222. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1223-1225. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1226-1228. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1229-1231. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1232-1234. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1235-1237. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1238-1240. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1241-1243. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1244-1246. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1247-1249. In some embodiments, the variable domain of the single domain antibody or antibody fragmentWSGR Docket Number: 63580-708.601 comprises the CDR1-3 of SEQ ID NOS: 1250-1252. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1253-1255. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1256-1258. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1259-1261. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1262-1264. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1265-1267. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1268-1270. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1271-1273. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1274-1276. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1277-1279. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1280-1282. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1283-1285. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1286-1288. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1289-1291. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1292-1294. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1295-1297. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1298-1300. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1301-1303. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1304-1306. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1307-1309. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1310-1312. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1313-1315. In some embodiments, the variable domain of the single domain antibody orWSGR Docket Number: 63580-708.601 antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1316-1318. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1319-1321. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1322-1324. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1325-1327. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1328-1330. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1331-1333. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1334-1336. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1337-1339. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1340-1342. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1343-1345. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1346-1348. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1349-1351. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1352-1354. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1355-1357. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1358-1360. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1361-1363. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1364-1366. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1367-1369.

[0124] Provided and exemplified herein are antibodies and antibody fragments that bind CA9, wherein the antibodies and / or antibody fragments comprise: a heavy chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VH selected from any one of the antibody clones in Table 10.WSGR Docket Number: 63580-708.601Table 10. Humanized CA9 VHH SequencesWSGR Docket Number: 63580-708.601

[0125] Provided and exemplified herein are antibodies and antibody fragments that bind CA9, wherein the antibodies and / or antibody fragments comprise: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1); a heavy chain complementarity determining region 2 (CDRH2); and a heavy chain complementarity determining region 3 (CDRH3). Such antibodies are provided in Table 11.Table 11WSGR Docket Number: 63580-708.601

[0126] In certain embodiments, the antibody or antibody fragment that binds CA9 comprises a heavy chain variable domain comprising a CDRH1-3 amino acid sequence selected from any one of the antibody clones in Table 11.

[0127] In some embodiments, the antibody or antibody fragment that binds CA9 comprises a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1241; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1242; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1243.

[0128] In certain embodiments, the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168.

[0129] In some embodiments, the antibody or antibody fragment that binds CA9 comprises a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1307; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1308; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1309.

[0130] In certain embodiments, the antibody or antibody fragment comprises: a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1190.WSGR Docket Number: 63580-708.601

[0131] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1386; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1387; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1388.

[0132] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1370.

[0133] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1389; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1390; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1391.

[0134] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1371.

[0135] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1392; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1393; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1394.

[0136] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1372.

[0137] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1395; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1396; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1397.WSGR Docket Number: 63580-708.601

[0138] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1373.

[0139] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1398; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1399; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1400.

[0140] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1374.

[0141] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1401; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1402; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1403.

[0142] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1375.

[0143] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1404; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1405; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1406.

[0144] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1376.

[0145] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1407; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQWSGR Docket Number: 63580-708.601ID NO: 1408; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1409.

[0146] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1377.

[0147] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1410; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1411; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1412.

[0148] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1378.

[0149] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1413; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1414; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1415.

[0150] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1379.

[0151] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1416; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1417; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1418.

[0152] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1380.

[0153] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1419; a heavy chainWSGR Docket Number: 63580-708.601 complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1420; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1421.

[0154] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1381.

[0155] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1422; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1423; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1424.

[0156] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1382.

[0157] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1425; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1426; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1427.

[0158] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1383.

[0159] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 1428; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1429; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1430.

[0160] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1384.

[0161] In some embodiments, the antibody or antibody fragment that binds CA9 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1WSGR Docket Number: 63580-708.601(CDRH1) comprising the amino acid sequence of SEQ ID NO: 1431; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 1432; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 1433.

[0162] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1385.ENPP3-binding antibodies and antibody fragments

[0163] Provided herein are antibodies and antibody fragments that bind ENPP3. Moreover, in certain instances, the antibodies and antibody fragments provided herein are also advantageous in that they target cell expressing ENPP3, e.g., cancer cells overexpressing ENPP3. In certain embodiments, the antibody and antibody fragment is a single-chain antibody. In certain embodiments, the single-chain antibody is a single chain variable fragment (scFGv).

[0164] Antibody is used in the broadest sense and generally refers to and / or includes monoclonal antibodies, multi-valent antibodies, multi-specific, single domain antibodies, and antigen-binding fragments of antibodies that bind ENPP3. Antibody fragments (also referred to as: antigen-binding antibody fragments) generally refer to and include antibody-derived proteins that comprise a functional set of CDRs (e.g., a CDRH1-3 and CDRL1-3 or a CDRH1-3 for a single domain antibody) that bind ENPP3, and have a molecular weight less than a full length IgG antibody (e.g., a molecular weight less than -150,000 Daltons). In certain embodiments, an antibody fragment (e.g., ENPP3-binding fragment) includes: fragment antigen binding (Fab) fragments, F(ab’)2 fragments, Fab’ fragments, Fv fragments, IgG (rlgG) fragments, a VH domain paired / complexed with a VL domain, and single chain antibody fragments, including single chain variable fragments (sFv or scFv). Single domain antibodies generally refer to an antibody having a single variable region that confers binding to a target protein, utilizing functional set of CDRs comprising a CDR1, CDR2, and CDR3. In certain instances for single domain antibodies, CDR1, CDR2, and CDR3 and CDRH1, CDRH2, and CDRH3 are used interchangeably. In certain embodiments, a single domain antibody is a VHH or comprises a VHH domain.

[0165] Antibodies and antigen-binding fragments of antibodies also include genetically engineered, and / or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multi-specific antibodies, multi-valent antibodies, diabodies, triabodies, and tetrabodies, tandem di-scFv, tandem tri-scFv. Antibodies also include full-lengthWSGR Docket Number: 63580-708.601 antibodies (also referred to as: an intact antibody and / or whole antibody) and also includes antibodies having a structure substantially similar to native antibodies, such as those having heavy chains that contain a CHI domain and an Fc region. Such Fc regions can be of any class or sub-class, including IgG and sub-classes thereof (e.g., IgGl and IgG4), IgM, IgE, IgA, and IgD.

[0166] ENPP3 generally refers to and / or includes the protein encoded by the ENPP3 gene. ENPP3 is generally known as ectonucleotide pyrophosphatase / phosphodiesterase family member 3, CD203c, BIO, NPP3, PDNP3, and PD-IBETA . In certain embodiments, the ENPP3 gene refers to NCBI GenelD 5169 and / or HGNC ID: HGNC: 3358, which includes sequence information on ENPP3. In certain embodiments, a ENPP3 protein refers to and includes the protein(s) of UniProt ID: 014638. In certain instances, ENPP3 comprises a protein comprising the amino acid sequence of SEQ ID NO: 2711.

[0167] Antibodies and / or antibody fragments described and exemplified herein bind ENPP3. Binding can be determined by bio-layer interferometry, surface plasmon resonance, isothermal titration calorimetry, and / or ELISA. Affinity generally refers to and / or includes the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody or antibody fragment) and its binding target (e.g., ENPP3). Affinity (i.e., the strength of binding interactions) can also be determined by any known method, such as by bio-layer interferometry, surface plasmon resonance, isothermal titration calorimetry, and / or ELISA. In certain embodiments, binding to ENPP3 can be determined by binding to recombinant ENPP3, e.g., a ENPP3 molecule having any one or any fragment of the amino acid sequences of Table 1. For example, Example 1 shows how binding can be determined for antibodies and antibody fragments that bind ENPP3. In some embodiments, the antibody or antibody fragment binds the ENPP3 with an affinity of less than about 100 nM, less than about 50 nM, less than about 25 nM, less than about 10 nM, less than about 5 nM, less than about 1 nM, less than about 0.5 nM or less than about 0.2 nM.

[0168] Complementarity determining regions (CDRs) generally comprise the amino acids within antibody variable regions that confer antigen specificity and / or binding affinity (e.g., to ENPP3). In general, there are three CDRs in each heavy chain variable region (CDRH1, CDRH2, CDRH3) and three CDRs in each light chain variable region (CDRL1, CDRL2, CDRL3). Framework regions (FRs) generally refer to and / or include non-CDR regions of the heavy and light chain variable regions. In general, there are four FRs in each full-length heavy chain variable region (FRH1, FRH2, FRH3, and FRH4), and four FRs in each full-length light chain variable region (FRL1, FRL2, FRL3, and FRL4).WSGR Docket Number: 63580-708.601

[0169] Variable regions (also referred to as variable domains) generally refer to and include the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen (e.g., a single variable domain comprises a CDR 1, CDR 2, and CDR 3). The variable domains of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three CDRs. In certain instances, a single VH or VL domain can be sufficient to confer antigen-binding specificity (e.g., binding to ENPP3).

[0170] Provided and exemplified herein are antibodies and antibody fragments that bind ENPP3, wherein the antibodies and / or antibody fragments comprise: (i) a light chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VL selected from any one of the antibody clones in Table 12, (ii) a heavy chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VH selected from any one of the antibody clones in Table 12, and (iii) a linker, wherein the VH and VL are selected from the same antibody and antibody fragment clone in Table 12. In some embodiments, the ENPP3 antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000.Table 12WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0171] Provided and exemplified herein are antibodies and antibody fragments that bind ENPP3, wherein the antibodies and / or antibody fragments comprise: (i) a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1; a light chain complementarity determining region 2 (CDRL2); and a light chain complementarity determiningWSGR Docket Number: 63580-708.601 region 3 (CDRL3); (ii) a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1); a heavy chain complementarity determining region 2 (CDRH2); and a heavy chain complementarity determining region 3 (CDRH3). Such antibodies are provided in Table 13. In some embodiments, the ENPP3 antibody or antibody fragment comprises the CDRs of the light chain variable region (VL) of SEQ ID NO: 2450, and the heavy chain variable region (VH) of SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises the CDRs of SEQ ID NO: 3000.Table 13WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0172] In certain embodiments, the antibody or antibody fragment that binds ENPP3 comprises(i) a light chain variable domain comprising the CDRL1-3 amino acid sequence selected from any one of the antibody clones in Table 13, and (ii) a heavy chain variable domain comprising a CDRH1-3 amino acid sequence selected from any one of the antibody clones in Table 13, wherein the CDRH1-3 and CDRL1-3 are selected from the same antibody clone in Table 13.

[0173] In certain embodiments, the antibody or antibody fragment that binds ENPP3 comprises: a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 2668; a heavy chainWSGR Docket Number: 63580-708.601 complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 2669; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 2670; and a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 2671; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 2672; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 2673.

[0174] In some embodiments, the ENPP3 antibody or antibody fragment comprises the CDRs of the light chain variable region (VL) of SEQ ID NO: 2450, and the heavy chain variable region (VH) of SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises the CDRs of SEQ ID NO: 3000.

[0175] In some embodiments, the ENPP3 antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and a heavy chain variable region (VH) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451. In some embodiments, the ENPP3 antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3000.

[0176] In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2351, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2352, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2350. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2354, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2355, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2353. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2357, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2358, and a linker.WSGR Docket Number: 63580-708.601In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2356. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2360, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2361, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2359. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2363, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2364, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2362. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2366, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2367, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2365. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2369, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2370, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2368. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2372, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2373, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2371. In certain embodiments, theWSGR Docket Number: 63580-708.601 antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2375, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2376, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2374. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2378, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2379, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2377. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2381, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2382, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2380. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2384, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2385, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2383. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2387, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2388, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2386. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2390, a heavy chain variableWSGR Docket Number: 63580-708.601 region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2391, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2389. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2393, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2394, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2392. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2396, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2397, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2395. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2399, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2400, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2398. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2402, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2403, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2401. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2405, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2406, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%,WSGR Docket Number: 63580-708.60185%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2404. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2408, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2409, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2407. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2411, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2412, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2410. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2414, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2415, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2413. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2417, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2418, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2416. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2420, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2421, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2419. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at leastWSGR Docket Number: 63580-708.60180%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2423, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2424, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2422. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2426, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2427, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2425. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2429, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2430, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2428. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2432, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2433, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2431. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2435, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2436, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2434. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2438, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identityWSGR Docket Number: 63580-708.601 to SEQ ID NO: 2439, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2437. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2441, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2442, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2440. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2444, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2445, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2443. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2447, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2448, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2446. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2449. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2453, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2454, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity toWSGR Docket Number: 63580-708.601SEQ ID NO: 2452. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2456, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2457, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2455. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2459, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2460, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2458. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2462, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2463, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2461. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2465, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2466, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2464. In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2468, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2469, and a linker. In some embodiments, the antibody or antibody fragment comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2467. The linker may connect the VH and VL to form a scFv. As a non-limiting example, the linker comprises GGGGSGGGGSGGGGS (SEQ ID NO: 3015).WSGR Docket Number: 63580-708.601

[0177] In certain embodiments, the antibody or antibody fragment comprises: a light chain variable region (VL) having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, a heavy chain variable region (VH) having at least 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451, and a linker. The linker may connect the VH and VL to form a scFv. As a nonlimiting example, the linker comprises GGGGSGGGGSGGGGS (SEQ ID NO: 3015).

[0178] In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2470-2472, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2473-2475. In some embodiments, the heavy chain variable domain comprises the CDR1- 3 of SEQ ID NOS: 2476-2478, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2479-2481. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2482-2484, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2485-2487. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2488-2490, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2491-2493. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2494-2496, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2497-2499. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2500-2502, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2503-2505. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2506- 2508, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2509-2511. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2512-2514, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2515- 2517. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2518-2520, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2521-2523. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2524-2526, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2527-2529. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2530-2532, and the light chain variable domain comprises the CDR1- 3 of SEQ ID NOS: 2533-2535. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2536-2538, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2539-2541. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2542-2544, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2545-2547. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2548-2550, and the lightWSGR Docket Number: 63580-708.601 chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2551-2553. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2554- 2556, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2557-2559. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2560-2562, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2563- 2565. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2566-2568, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2569-2571. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2572-2574, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2575-2577. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2578-2580, and the light chain variable domain comprises the CDR1- 3 of SEQ ID NOS: 2581-2583. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2584-2586, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2587-2589. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2590-2592, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2593-2595. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2596-2598, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2599-2601. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2602- 2604, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2605-2607. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2608-2610, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2611- 2613. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2614-2616, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2617-2619. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2620-2622, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2623-2625. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2626-2628, and the light chain variable domain comprises the CDR1- 3 of SEQ ID NOS: 2629-2631. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2632-2634, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2635-2637. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2638-2640, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2641-2643. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2644-2646, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2647-2649. In someWSGR Docket Number: 63580-708.601 embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2650- 2652, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2653-2655. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2656-2658, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2659- 2661. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2662-2664, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2665-2667. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2668-2670, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2671-2673. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2674-2676, and the light chain variable domain comprises the CDR1- 3 of SEQ ID NOS: 2677-2679. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2680-2682, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2683-2685. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2686-2688, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2689-2691. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2692-2694, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2695-2697. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2698- 2700, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2701-2703. In some embodiments, the heavy chain variable domain comprises the CDR1-3 of SEQ ID NOS: 2704-2706, and the light chain variable domain comprises the CDR1-3 of SEQ ID NOS: W1- 2709.

[0179] Provided and exemplified herein are antibodies and antibody fragments that bind ENPP3, wherein the antibodies and / or antibody fragments comprise: a heavy chain variable domain comprising an amino acid sequence having at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a VH selected from any one of the antibody clones in Table 14.Table 14WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0180] Provided and exemplified herein are single domain antibodies and antibody fragments that bind ENPP3, wherein the single domain antibodies and / or antibody fragments comprise: (i) a heavy chain variable region comprising: a heavy chain complementarity determining region 1 (CDRH1); a heavy chain complementarity determining region 2 (CDRH2); and a heavy chain complementarity determining region 3 (CDRH3). Such antibodies are provided in Table 15.Table 15WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601WSGR Docket Number: 63580-708.601

[0181] In certain embodiments, the antibody or antibody fragment that binds ENPP3 comprises a heavy chain variable domain comprising a CDRH1-3 amino acid sequence selected from any one of the antibody clones in Table 15.

[0182] In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1434. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1435. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1436. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1437. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1438. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1439. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1440. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1441. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1442. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1443. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1444. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1445. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1446. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1447. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1448. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1449. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1450. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1451. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1452. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1453. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1454. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1455. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1456. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1457. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1458. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1459. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1460. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1461. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1462. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1463. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1464. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1465. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1466. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1467. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1468. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1469. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1470. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1471. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1472. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1473. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1474. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1475. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1476. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1477. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1478. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1479. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1480. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1481. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1482. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1483. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1484. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1485. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1486. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1487. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1488. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1489. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1490. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1491. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1492. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1493. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1494. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1495. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1496. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1497. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1498. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1499. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1500. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1501. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1502. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1503. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1504. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1505. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1506. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1507. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1508. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1509. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1510. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1511. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1512. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1513. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1514. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1515. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1516. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1517. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1518. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1519. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1520. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1521. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1522. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1523. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1524. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1525. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1526. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1527. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1528. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1529. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1530. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1531. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1532. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1533. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1534. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1535. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1536. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1537. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1538. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1539. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1540. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1541. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1542. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1543. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1544. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1545. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1546. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1547. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1548. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1549. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1550. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1551. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1552. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1553. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1554. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1555. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1556. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1557. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1558. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1559. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1560. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1561. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1562. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1563. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1564. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1565. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1566. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1567. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1568. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1569. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1570. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1571. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,WSGR Docket Number: 63580-708.60199%, or 100% sequence identity to SEQ ID NO: 1572. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1573. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1574. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1575. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1576. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1577. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1578. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1579. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1580. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1581. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1582. In certain embodiments, the single domain antibody or antibody fragment comprises: a variable region having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1583.

[0183] In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1584-1586. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1587-1589. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1590-1592. In some embodiments, the variable domain of the single domain antibody or antibody fragmentWSGR Docket Number: 63580-708.601 comprises the CDR1-3 of SEQ ID NOS: 1593-1595. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1596-1598. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1599-1601. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1602-1604. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1605-1607. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1608-1610. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1611-1613. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1614-1616. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1617-1619. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1620-1622. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1623-1625. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1626-1628. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1629-1631. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1632-1634. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1635-1637. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1639-1640 and AMA. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1641-1643. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1644-1646. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1647-1649. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1650-1652. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1653-1655. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1656-1658. In some embodiments, the variable domain of the single domainWSGR Docket Number: 63580-708.601 antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1659-1661. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1662-1664. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1665-1667. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1668-1670. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1672-1673 and AMA. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1674-1676. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1677-1679. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1681-1682 and AMA. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1683-1685. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1686-1688. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1689-1691. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1692-1694. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1695-1697. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1698-1700. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1701-1703. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1704-1706. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1707-1709. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1710-1712. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1713-1715. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1716-1718. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1719-1721. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1722-1724. In some embodiments,WSGR Docket Number: 63580-708.601 the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1725-1727. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1728-1730. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1731-1733. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1734-1736. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1737-1739. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1740-1742. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1743-1745. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1746-1748. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1749-1751. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1752-1754. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1755-1757. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1759-1760 and AMA. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1761-1763. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1764-1766. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1767-1769. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1770-1772. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1773-1775. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1776-1778. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1779-1781. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1782-1784. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1785-1787. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1788-1790. In someWSGR Docket Number: 63580-708.601 embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1791-1793. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1794-1796. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1797-1799. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1800-1802. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1803-1805. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1806-1808. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1809-1811. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1812-1814. In some embodiments, the variable domain of the single domain antibody or antibody fragment comprises the CDR1-3 of SEQ ID NOS: 1815-1817. I...

Claims

WSGR Docket Number: 63580-708.601CLAIMSWhat is Claimed:

1. A pharmaceutical composition comprising a first fusion protein comprising an antibody or antibody fragment that binds ENPP3, and a second fusion protein comprising an antibody or antibody fragment that binds CA9, wherein:(a) the antibody or antibody fragment that binds ENPP3 comprises: (i) a heavy chain variable domain comprising: a heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence of SEQ ID NO: 2668; a heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence of SEQ ID NO: 2669; and a heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence of SEQ ID NO: 2670; and (ii) a light chain variable domain comprising: a light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence of SEQ ID NO: 2671; a light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence of SEQ ID NO: 2672; and a light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence of SEQ ID NO: 2673; (ii) a variable heavy domain of heavy chain (VHH) comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 2106; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 2107; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 2108; or (iii) a variable heavy domain of heavy chain (VHH) comprising: a CDRH1 comprising the amino acid sequence of SEQ ID NO: 2109; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 2110; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 2111; and(b) the antibody or antibody fragment that binds CA9 comprises a variable heavy domain of heavy chain (VHH) comprising: (i) a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1241; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 1242; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 1243; (ii) a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1307; a CDRH2 comprising the amino acid sequence of SEQ ID NO: 1308; and a CDRH3 comprising the amino acid sequence of SEQ ID NO: 1309.

2. The pharmaceutical composition of claim 1, wherein the first fusion protein comprises a LAT polypeptide and the second fusion protein comprises a SLP76 polypeptide.

3. The pharmaceutical composition of claim 2, wherein the LAT polypeptide comprises any one of SEQ ID NOS: 2714, 2715, 2723, 2724, or 3007-3014; and the SLP76 polypeptide comprises SEQ ID NO: 2712 or 2713.WSGR Docket Number: 63580-708.6014. The pharmaceutical composition of claim 3, wherein the LAT polypeptide comprises SEQ ID NO: 3009, optionally wherein the LAT polypeptide does not comprise amino acids 1-63 of SEQ ID NO: 2723 or amino acids 173-235 of SEQ ID NO: 2723; and the SLP76 polypeptide comprises SEQ ID NO: 2712.

5. The pharmaceutical composition of any one of claims 1-4, wherein the antibody or antibody fragment that binds CA9 comprises (b)(i), and the VHH has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1168.

6. The pharmaceutical composition of any one of claims 1-4, wherein the antibody or antibody fragment that binds CA9 comprises (b)(i), and the VHH has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1190.

7. The pharmaceutical composition of any one of claims 1-6, wherein the antibody or antibody fragment that binds ENPP3 comprises (a)(ii), and the VHH has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2035.

8. The pharmaceutical composition of any one of claims 1-6, wherein the antibody or antibody fragment that binds ENPP3 comprises (a)(iii), and the VHH has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2036.

9. The pharmaceutical composition of any one of claims 1-6, wherein the antibody or antibody fragment that binds ENPP3 comprises (a)(i), and the light chain variable region (VL) has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2450, and the heavy chain variable region (VH) has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2451.

10. The pharmaceutical composition of any one of claims 1-6, wherein the antibody or antibody fragment that binds ENPP3 comprises (a)(i), and a sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2449 or SEQ ID NO: 3000.

11. A pharmaceutical composition comprising:(a) a first chimeric antigen receptor (CAR) polypeptide comprising:(i) an antibody or antibody fragment having a binding affinity for a CA9 protein;(ii) a first transmembrane domain; andWSGR Docket Number: 63580-708.601(iii) a first intracellular signaling domain; and(b) a second chimeric antigen receptor (CAR) polypeptide comprising:(i) an antibody or antibody fragment having a binding affinity for an ENPP3 protein;(ii) a second transmembrane domain; and(iii) a second intracellular signaling domain different from the first ligand, wherein the binding affinity for the CA9 protein is lower compared to the binding affinity for the ENPP3 protein.

12. The pharmaceutical composition of claim 11, wherein the binding affinity for the CA9 protein is between about 10 micromolar to about 1 micromolar.

13. The pharmaceutical composition of claim 11 or claim 12, wherein the binding affinity for the ENPP3 protein is between about 50 x 1 O’9M, to about 5 x 1 O’9M.

14. The pharmaceutical composition of claim 11, wherein the binding affinity for the CA9 protein comprises a dissociation rate constant (koff) between about 1.0 x 10’3S'1to about 5.0 x IO’3S’1.

15. The pharmaceutical composition of claim 11, wherein the binding affinity for the CA9 protein comprises a dissociation rate constant (koff) between about 1.0 x 10’4S'1to about 5.0 x IO’4S’1.

16. The pharmaceutical composition of claim 11, wherein the binding affinity for the CA9 protein comprises a dissociation rate constant (koff) between about 1.0 x 10’5S'1to about 5.0 x IO’5S’1.

17. The pharmaceutical composition of claim 11, wherein the binding affinity for the ENPP3 protein comprises a dissociation rate constant (koff) between about 1.0 x 10’3S'1to about 5.0 x IO’3S’1.

18. The pharmaceutical composition of claim 11, wherein the binding affinity for the ENPP3 protein comprises a dissociation rate constant (koff) between about 1.0 x 10’4S'1to about 5.0 x IO’4S’1.

19. The pharmaceutical composition of claim 11, wherein the binding affinity for the ENPP3 protein comprises a dissociation rate constant (koff) between about 1.0 x 10’5S'1to about 5.0 x IO’5S’1.

20. The pharmaceutical composition of claim 11, wherein the binding affinity for the ENPP3 protein comprises a dissociation rate constant (koff) of about 1.0 x 10’6S’1, about 2.0 x 10’6S’1, about 3.0 x 10’6S’1, about 4.0 x 10’6S’1, or about 5.0 x 10’6S’1.WSGR Docket Number: 63580-708.60121. The pharmaceutical composition of any one of claims 11-20, wherein binding of the first extracellular ligand-binding domain to the CA9 protein, in absence of binding of the second extracellular ligand-binding domain to the ENPP3 protein, does not activate the first intracellular signaling domain.

22. The pharmaceutical composition of any one of claims 1-21, wherein the antibody or antibody fragment that binds ENPP3 does not bind to a cell with low expression of ENPP3, and the antibody or antibody fragment that binds CA9 does not bind to a cell with low expression of CA9.

23. A nucleic acid composition comprising a nucleic acid encoding the first fusion protein of any one of claims 1-22, and a nucleic acid encoding the second fusion protein of any one of claims 1-22.

24. The nucleic acid composition of claim 23, wherein the nucleic acid composition is a viral vector.

25. A lymphocyte comprising the pharmaceutical composition of any one of claims 1-22, or the nucleic acid composition of claim 23 or claim 24.

26. The lymphocyte of claim 25, wherein the lymphocyte is a T cell, a NK cell, or a NKT cell.

27. A method of inhibiting proliferation of a cell expressing CA9 and ENPP3, the method comprising: contacting a cell with the pharmaceutical composition of any one of claims 1-22, the nucleic acid composition of claim 23 or claim 24, or the lymphocyte of claim 25 or claim 26.

28. A method of treating clear cell renal cell carcinoma, the method comprising administering to a subject in need thereof the pharmaceutical composition of any one of claims 1-22, the nucleic acid composition of claim 23 or claim 24, or the lymphocyte of claim 25 or claim 26.

29. The method of claim 28, wherein prior to the administering, the subject was treated with a cancer therapy.

30. The method of claim 29, wherein the cancer therapy comprises an immuno-oncology therapy, a tyrosine kinase inhibitor, or a HIF inhibitor, or a combination of two or more thereof.

31. The method of any one of claims 28-30, wherein prior to the administering, the CA9 and / or the ENPP3 is detected from a sample obtained from the subject, optionally wherein the CA9 or the ENPP3 is detected using immunohistochemistry or positron emission tomography.

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