Anti-GAL3 Antibodies and Methods for Use in Insulin Resistance

Abstract

Disclosed herein are methods and compositions for disrupting the interaction between galectin-3 and insulin receptor or glucose transporter.Furthermore, disclosed herein are methods and compositions for treating disease or disorder in a subject, such as diabetes mellitus, insulin resistance, chronic hyperinsulinemia, metabolic syndrome, insulin resistance type A, insulin resistance type B, gestational diabetes, acanthosis nigricans, polycystic ovarian syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), rhabdomyosarcoma, or cancer treatment.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63 / 202,373, filed June 8, 2021, which is expressly incorporated herein by reference in its entirety.

[0002] Sequence Listing Reference This application is being filed with an electronic Sequence Listing, which is provided as a file named SeqListingIMMUT029WO.TXT, was created and last updated on June 7, 2022, and is 1,984,218 bytes in size. The information in this electronic Sequence Listing is incorporated herein by reference in its entirety.

[0003] Technical Field Aspects of the present disclosure generally relate to antibodies or binding fragments thereof that block or disrupt the interaction between galectin-3 (Gal3) and insulin receptor (INSR) or glucose transporters, such as glucose transporter 1 (GLUT1) or glucose transporter 4 (GLUT4). [Background technology]

[0004] Galectin-3 (Gal3, GAL3) is a lectin, i.e., a carbohydrate-binding protein, with specificity for β-galactosides. In human cells, Gal3 is expressed and can be found in the nucleus, cytoplasm, cell surface, and extracellular space. Gal3 recognizes and interacts with β-galactose conjugates on various proteins. Summary of the Invention

[0005] Aspects of the present disclosure generally relate to antibodies or binding fragments thereof that block or disrupt the interaction between galectin-3 (Gal3) and the insulin receptor (INSR) or glucose transporters, such as glucose transporter 1 (GLUT1) or glucose transporter 4 (GLUT4). Additionally, disclosed herein are methods and compositions for the treatment of diseases or disorders that may be associated with impaired INSR and / or GLUT function, such as, but not limited to, diabetes mellitus, insulin resistance, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), rhabdomyosarcoma, or cancer.

[0006] Galectin-3 (Gal3) has been suggested to have immunomodulatory activity. An example of this is the interaction between Gal3 and T cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3), which can cause suppression of immune responses, such as T cell activation, allowing cancer cells to evade immune clearance. This phenomenon and methods for inhibiting this phenomenon are exemplified in International Publication Nos. 2019 / 023247 and 2020 / 160156, each of which is expressly incorporated herein by reference in its entirety.

[0007] Disclosed herein are anti-Gal3 antibodies or binding fragments thereof. In some embodiments, the antibodies or binding fragments thereof are H -CDR1, V H -CDR2, and V H - a heavy chain variable region comprising CDR3; and V L -CDR1, V L -CDR 2, and V L In some embodiments, the V H- CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 32, 37, or 66. In some embodiments, the V H - CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 801, 951, 952, 77, or 108. In some embodiments, the V H - CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 953, 954, 802, 118, or 164. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 171, 178, or 215. In some embodiments, the V L - CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 222, 229, or 225. In some embodiments, the V L- CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 257, 256, or 291.

[0008] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 806-820, 955-968, 1067-1109, or 1415-1439. In some embodiments, the light chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 821-835, 969-982, 1110-1152, or 1440-1464. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 836-850, 983-996, 1411, 1153-1195, or 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 851-865, 997-1010, 1196-1238, 1412, or 1490-1514.

[0009] Also disclosed herein are nucleic acids comprising a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the nucleic acid sequences of SEQ ID NOs: 866-925, 1011-1066, 1239-1410, 1413-1414, or 1515-1614.

[0010] Also disclosed herein are methods for enhancing glucose transporter (GLUT) translocation in cells. In some embodiments, the methods can include contacting a cell with an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the glucose transporter is glucose transporter 1 (GLUT1) and / or glucose transporter 4 (GLUT4). In some embodiments, binding of the anti-Gal3 antibody or binding fragment thereof to Gal3 in the cell inhibits blockage of Gal3-mediated GLUT translocation. In some embodiments, the methods are performed in vitro or in vivo. In some embodiments, GLUT translocation in cells is enhanced by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% after contact with the anti-Gal3 antibody or binding fragment thereof compared to cells not contacted with the anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment is any one or more of the above anti-Gal3 antibodies or binding fragments thereof disclosed herein, or any portion or component of any one or more of the above anti-Gal3 antibodies or binding fragments thereof, including, but not limited to, one, two, three, four, five, or six CDRs, heavy chain variable region, light chain variable region, heavy chain, or light chain.

[0011] Also disclosed herein are methods for enhancing glucose transporter (GLUT) translocation in cells. In some embodiments, the methods can include contacting cells with a complex formed by preincubating Gal3 with an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the glucose transporter is glucose transporter 1 (GLUT1) and / or glucose transporter 4 (GLUT4). In some embodiments, the methods are performed in vitro or in vivo. In some embodiments, GLUT translocation in cells is enhanced by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% after contacting cells with a complex of Gal3 preincubated with an anti-Gal3 antibody or binding fragment thereof compared to cells not contacted with a complex of Gal3 preincubated with an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment is any one or more of the above anti-Gal3 antibodies or binding fragments thereof disclosed herein, or any portion or component of any one or more of the above anti-Gal3 antibodies or binding fragments thereof, including, but not limited to, one, two, three, four, five, or six CDRs, heavy chain variable region, light chain variable region, heavy chain, or light chain.

[0012] Also disclosed herein is a method for improving insulin sensitivity in a subject in need thereof. In some embodiments, the method may include administering an anti-Gal3 antibody or binding fragment thereof to a subject. In some embodiments, binding of the anti-Gal3 antibody or binding fragment thereof to Gal3 in the subject inhibits blockage of Gal3-mediated GLUT translocation in the subject, thereby improving insulin sensitivity in the subject. In some embodiments, the GLUT is glucose transporter 1 (GLUT1) and / or glucose transporter 4 (GLUT4). In some embodiments, the method further includes identifying a subject in need of improved insulin sensitivity prior to the administering step. In some embodiments, the method further includes detecting improved insulin sensitivity in the subject after the administering step. In some embodiments, detecting improved insulin sensitivity in the subject is performed by measuring blood glucose levels, measuring blood insulin levels, a glucose tolerance test, or a hyperinsulinemic-euglycemic clamp. In some embodiments, the insulin sensitivity in the subject is improved by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% compared to the subject's insulin sensitivity before the administering step. In some embodiments, the anti-Gal3 antibody or binding fragment is any one or more of the above anti-Gal3 antibodies or binding fragments thereof disclosed herein, or any portion or component of any one or more of the above anti-Gal3 antibodies or binding fragments thereof, including, but not limited to, one, two, three, four, five, or six CDRs, heavy chain variable region, light chain variable region, heavy chain, or light chain.

[0013] Also disclosed herein are methods for improving insulin sensitivity in a subject in need thereof. In some embodiments, the method may include improving insulin sensitivity in the subject by administering to the subject a complex preincubated with Gal3 and an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the GLUT is glucose transporter 1 (GLUT1) and / or glucose transporter 4 (GLUT4). In some embodiments, the method further includes identifying a subject in need of improved insulin sensitivity prior to the administering step. In some embodiments, the method further includes detecting improved insulin sensitivity in the subject after the administering step. In some embodiments, detecting improved insulin sensitivity in the subject is performed by measuring blood glucose levels, measuring blood insulin levels, a glucose tolerance test, or a hyperinsulinemic-euglycemic clamp. In some embodiments, the insulin sensitivity in the subject is improved by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% compared to the subject's insulin sensitivity before the administering step. In some embodiments, the anti-Gal3 antibody or binding fragment is any one or more of the above anti-Gal3 antibodies or binding fragments thereof disclosed herein, or any portion or component of any one or more of the above anti-Gal3 antibodies or binding fragments thereof, including, but not limited to, one, two, three, four, five, or six CDRs, heavy chain variable region, light chain variable region, heavy chain, or light chain.

[0014] Also disclosed herein are methods for treating a disease associated with insulin resistance in a subject in need thereof. In some embodiments, the method may include treating the disease associated with insulin resistance in a subject by administering to the subject an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the insulin Resistance-associated diseases include diabetes mellitus, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer. In some embodiments, the method further comprises identifying a subject in need of treatment for the insulin resistance-associated disease prior to the administering step. In some embodiments, the method further comprises detecting an improvement in the insulin resistance-associated disease after the administering step. In some embodiments, detecting an improvement in the insulin resistance-associated disease comprises detecting an improvement in insulin sensitivity in the subject. In some embodiments, detecting an improvement in insulin sensitivity in the subject is performed by measuring blood glucose levels, measuring blood insulin levels, a glucose tolerance test, or a hyperinsulinemic-euglycemic clamp. In some embodiments, the insulin sensitivity in the subject is improved by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% compared to the subject's insulin sensitivity before the administering step. In some embodiments, the anti-Gal3 antibody or binding fragment is any one or more of the above anti-Gal3 antibodies or binding fragments thereof disclosed herein, or any portion or component of any one or more of the above anti-Gal3 antibodies or binding fragments thereof, including, but not limited to, one, two, three, four, five, or six CDRs, heavy chain variable region, light chain variable region, heavy chain, or light chain.

[0015] Also disclosed herein are methods for treating a disease associated with insulin resistance in a subject in need thereof. In some embodiments, the method may include treating the disease associated with insulin resistance in a subject by administering to the subject a complex preincubated with Gal3 and an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the disease associated with insulin resistance includes diabetes mellitus, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer. In some embodiments, the method further includes identifying a subject in need of treatment for the disease associated with insulin resistance prior to the administering step. In some embodiments, the method further includes detecting an improvement in the disease associated with insulin resistance after the administering step. In some embodiments, detecting an improvement in the disease associated with insulin resistance includes detecting an improvement in insulin sensitivity in the subject. In some embodiments, detecting improved insulin sensitivity in the subject is performed by measuring blood glucose levels, measuring blood insulin levels, a glucose tolerance test, or a hyperinsulinemic-euglycemic clamp. In some embodiments, the insulin sensitivity in the subject is improved by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% compared to the subject's insulin sensitivity before the administering step.In some embodiments, the anti-Gal3 antibody or binding fragment is any one or more of the above anti-Gal3 antibodies or binding fragments thereof disclosed herein, or any portion or component of any one or more of the above anti-Gal3 antibodies or binding fragments thereof, including, but not limited to, one, two, three, four, five, or six CDRs, heavy chain variable region, light chain variable region, heavy chain, or light chain. [Brief explanation of the drawings]

[0016] In addition to the features described above, further features and modifications will be readily apparent from the following description of the drawings and exemplary embodiments, which should be understood to illustrate typical embodiments and are not intended to be limiting in scope. [Figure 1] Figure 1 shows the ability of galectin-3-targeting antibodies at 10 μg / mL, 3 μg / mL, and 1 μg / mL to block binding of Gal3 to the insulin receptor (INSR) as measured by enzyme-linked immunosorbent assay (ELISA). Bars represent mean ± standard deviation. [Figure 2] Figure 2 shows the titration of a limited series of galectin-3-targeting antibodies to block binding of Gal3 to the insulin receptor (INSR) as measured by enzyme-linked immunosorbent assay (ELISA). Bars represent mean ± standard deviation. [Figure 3A] FIG. 3A provides a summary of the properties of exemplary anti-Gal3 antibodies. [Figure 3B] Figure 3B shows the identification of Gal3-binding antibody bins by antibody competition. Values ​​represent inhibition as assessed by biolayer interference. [Figure 4]Figure 4 shows reduced weight gain in mice fed a normal diet or a 60% high-fat diet (HFD) for 8 weeks and administered the isotype control antibody HuIgG4 or Gal3-targeted TB001 (IMT001-4). The left panel shows the absolute mean, and the right panel shows the mean percent gain / loss per animal ± standard error. [Figure 5] Figure 5 shows glucose tolerance in mice treated as in Figure 4. The left panel shows the mean serum glucose values ​​after the glucose bolus; the right panel shows the mean area under the curve (AUC) + / - 1 standard error obtained from the data shown in the left panel. [Figure 6] Figure 6 shows insulin resistance in mice treated as in Figure 4. The left panel shows the mean serum glucose values ​​after the insulin bolus; the right panel shows the mean area under the curve (AOC) + / - 1 standard error obtained from the data shown in the left panel. [Figure 7] Figure 7 shows hematoxylin and eosin staining of formalin-fixed, paraffin-embedded liver sections obtained from mice treated with the treatments in Figure 4. Note the evidence of steatosis in HFD-fed mice treated with control IgG4 and the absence of it in HFD-fed mice treated with IMT001-4 (TB001). [Figure 8] Figure 8 shows serum levels of the liver enzyme ALT in mice treated as in Figure 4. Bars represent the mean ± standard error. [Figure 9] FIG. 9 shows the amount of circulating Gal3 in Bks-Db or C57BL6 / J control mice. [Figure 10] Figure 10 shows Kaplan-Meier curves for healthy C57BL6 / J and Db / Db mice treated with the anti-Gal3 antibody mTB001, the negative control PBS, or the positive control semaglutide. [Figure 11]FIG. 11 shows the changes in fasting blood glucose levels in healthy C57BL6 / J or Db / Db mice treated with either mTB001 or PBS. [Figure 12] FIG. 12 shows the mean survival time of NOD / ShiLtJ mice treated with mTB001 compared to the untreated control group. [Figure 13A] FIG. 13A shows the change in fasting blood glucose levels in NOD / ShiLtJ mice treated with mTB001 compared to the untreated control group. [Figure 13B] FIG. 13B shows the blood levels of C-peptide in NOD / ShiLtJ mice treated with mTB001 and in normal control mice compared to untreated controls. [Figure 14] FIG. 14 shows the primers used for RT-qPCR to quantify inflammatory cytokines in an inflammatory bowel disease (IBD) mouse model. [Figure 15] FIG. 15 shows the measured colon length in DSS-induced IBD mice treated with mTB001 or PBS compared to normal mice. [Figure 16] FIG. 16 shows the quantification of circulating IFN-γ in DSS-induced IBD mice treated with mTB001 (10 mg / kg and 1 mg / kg) or PBS compared to normal mice. [Figure 17] FIG. 17 shows the protein sequences of Gal3, insulin receptor (INSR), glucose transporter 4 (GLUT4), and glucose transporter 1 (GLUT1). [Figure 18] FIG. 18 shows the peptide sequences of Gal3 used to generate and analyze antibodies. [Figure 19A]19A shows exemplary heavy chain variable region complementarity determining region (CDR) 1 for the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy chain variable region CDR1s provided herein. [Figure 19B] 19B shows exemplary heavy chain variable region CDR2s for the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy chain variable region CDR2s provided herein. [Figure 19C] 19C shows exemplary heavy chain variable region CDR3s for the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy chain variable region CDR3s provided herein. [Figure 20A] Figure 20A shows exemplary light chain variable region CDR1s for the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the light chain variable region CDR1s provided herein. [Figure 20B] Figure 20B shows exemplary light chain variable region CDR2s for the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the light chain variable region CDR2s provided herein. [Figure 20C] Figure 20C shows exemplary light chain variable region CDR3s for the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the light chain variable region CDR3s provided herein. [Figure 21-01]21 shows exemplary heavy chain variable region (VH) sequences for the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the VH sequences provided herein. [Figure 21-02] Figure 21 (continued) [Figure 21-03] Figure 21 (continued) [Figure 21-04] Figure 21 (continued) [Figure 21-05] Figure 21 (continued) [Figure 21-06] Figure 21 (continued) [Figure 21-07] Figure 21 (continued) [Figure 21-08] Figure 21 (continued) [Figure 21-09] Figure 21 (continued) [Figure 21-10] Figure 21 (continued) [Figure 21-11] Figure 21 (continued) [Figure 21-12] Figure 21 (continued) [Figure 21-13] Figure 21 (continued) [Figure 22-01] 22 shows exemplary light chain variable region (VL) sequences for the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the VL sequences provided herein. [Figure 22-02] Figure 22 (continued) [Figure 22-03] Figure 22 (continued) [Figure 22-04] Figure 22 (continued) [Figure 22-05] Figure 22 (continued) [Figure 22-06] Figure 22 (continued) [Figure 22-07] Figure 22 (continued) [Figure 22-08] Figure 22 (continued) [Figure 22-09] Figure 22 (continued) [Figure 22-10] Figure 22 (continued) [Figure 22-11] Figure 22 (continued) [Figure 23-1] Figure 23 shows exemplary combinations of heavy and light chain CDRs (CDR1, CDR2, and CDR3) of exemplary anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more of the combinations of heavy and light chain CDRs provided herein. [Figure 23-2] Figure 23 (continued) [Figure 23-3] Figure 23 (continued) [Figure 23-4] Figure 23 (continued) [Figure 23-5] Figure 23 (continued) [Figure 23-6] Figure 23 (continued) [Figure 24-1] 24 shows exemplary heavy and light chain variable region combinations of exemplary anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy and light chain variable region combinations provided herein. [Figure 24-2] Figure 24 (continued) [Figure 24-3] Figure 24 (continued) [Figure 24-4] Figure 24 (continued) [Figure 24-5] Figure 24 (continued) [Figure 24-6] Figure 24 (continued) [Figure 25-01] 25 shows exemplary heavy chain (HC) and light chain (LC) sequences and a table of possible combinations for exemplary anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the HC or LC sequences, or pairs of HC and LC sequences, provided herein. [Figure 25-02] Figure 25 (continued) [Figure 25-03] Figure 25 (continued) [Figure 25-04] Figure 25 (continued) [Figure 25-05] Figure 25 (continued) [Figure 25-06] Figure 25 (continued) [Figure 25-07] Figure 25 (continued) [Figure 25-08] Figure 25 (continued) [Figure 25-09] Figure 25 (continued) [Figure 25-10] Figure 25 (continued) [Figure 25-11] Figure 25 (continued) [Figure 25-12] Figure 25 (continued) [Figure 25-13] Figure 25 (continued) [Figure 25-14] Figure 25 (continued) [Figure 25-15] Figure 25 (continued) [Figure 25-16] Figure 25 (continued) [Figure 25-17] Figure 25 (continued) [Figure 25-18] Figure 25 (continued) [Figure 25-19] Figure 25 (continued) [Figure 25-20] Figure 25 (continued) [Figure 25-21] Figure 25 (continued) [Figure 25-22] Figure 25 (continued) [Figure 25-23] Figure 25 (continued) [Figure 25-24] Figure 25 (continued) [Figure 25-25] Figure 25 (continued) [Figure 25-26] Figure 25 (continued) [Figure 25-27] Figure 25 (continued) [Figure 25-28] Figure 25 (continued) [Figure 25-29] Figure 25 (continued) [Figure 25-30] Figure 25 (continued) [Figure 25-31] Figure 25 (continued) [Figure 25-32] Figure 25 (continued) [Figure 25-33] Figure 25 (continued) [Figure 25-34] Figure 25 (continued) [Figure 25-35]Figure 25 (continued) [Figure 25-36] Figure 25 (continued) [Figure 25-37] Figure 25 (continued) [Figure 25-38] Figure 25 (continued) [Figure 25-39] Figure 25 (continued) [Figure 25-40] Figure 25 (continued) [Figure 25-41] Figure 25 (continued) [Figure 25-42] Figure 25 (continued) [Figure 26-1] Figure 26 shows peptides (following the peptide names shown in Figure 18 as discussed herein) that were found to bind to exemplary anti-Gal3 antibodies disclosed herein, and the bins of these exemplary antibodies. [Figure 26-2] Figure 26 (continued) [Figure 27] FIG. 27 shows the KD(M) values ​​for Gal3 binding for exemplary anti-Gal3 antibodies disclosed herein. [Figure 28] FIG. 28 shows the antibody affinity (KD) of anti-Gal3 humanized antibodies IMT001 and IMT006a to human Gal3, cynomolgus monkey Gal3, and mouse Gal3. [Figure 29] Figure 29 shows antibody names used throughout this disclosure that refer to the same antibody (with exemplary peptide and nucleic acid sequences provided elsewhere in this disclosure and appropriately assigned at least one of the names shown) and may be used interchangeably. Names shown in columns correspond to the same antibody. [Figure 30] Figure 30 shows a graph of relative GLUT4 translocation, determined as the fold change between insulin-stimulated cells and insulin-unstimulated (basal) cells ± Gal3 contacted with various exemplary anti-Gal3 antibodies (or no antibody control), as measured in an immunocytochemistry-based assay. Antibody 2D10 here refers to 2D10-VH0-VL0. [Figure 31A]Figures 31A-B show graphs of relative GLUT4 translocation, calculated as the fold change between insulin-stimulated cells and insulin-unstimulated (basal) cells ± Gal3 contacted with 20H5 variants (Figure 31A) or 2D10-VH0-VL0(2D10) variants (Figure 31B) (or no antibody control), as measured by an immunocytochemistry-based assay. [Figure 31B] Figures 31A-B show graphs of relative GLUT4 translocation, calculated as the fold change between insulin-stimulated cells and insulin-unstimulated (basal) cells ± Gal3 contacted with 20H5 variants (Figure 31A) or 2D10-VH0-VL0(2D10) variants (Figure 31B) (or no antibody control), as measured by an immunocytochemistry-based assay. [Figure 32-1]Figure 32 shows the alignment of the hinge domain and heavy chain constant domain 2 (CH2) amino acid sequences of wild-type human immunoglobulin G1 (IgG1), wild-type IgG2, and wild-type IgG4, as well as their Sigma variants. The alignment uses the EU numbering system. Residues identical to wild-type IgG1 are represented as dots; gaps are represented by hyphens. Differences from wild-type IgG1 are indicated by the sequence designation, and for σ variants, differences from the parent subtype are indicated by the sequence designation. The open boxes below the alignment correspond to the International Immunogenetics Information System (IMGT) chain definitions. The boxes below the alignment correspond to the chain and helix secondary structure assignments for wild-type IgG1. Residues 267-273 form the BC loop, and residues 322-332 form the FG loop. Also shown are exemplary constant regions for the heavy (S228P mutant) and light (κ) chains of human IgG4 (SEQ ID NOs: 945-946), mouse IgG2A (LALAPG and LALA mutants) (SEQ ID NOs: 947-948), and human IgG1 (KEM, REM, and LALAPGv2 mutants) (SEQ ID NOs: 1615-1617). In some embodiments, any one or more of the VH / VL and / or CDRs provided in other figures or disclosed herein may be paired with any one or more of the exemplary constant regions provided herein. [Figure 32-2] Figure 32 (continued) [Figure 32-3] Figure 32 (continued) [Figure 33-01] Figure 33 shows nucleic acid sequences encoding exemplary heavy chain variable regions of the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy chain variable regions provided herein. [Figure 33-02] Figure 33 (continued) [Figure 33-03] Figure 33 (continued) [Figure 33-04] Figure 33 (continued) [Figure 33-05] Figure 33 (continued) [Figure 33-06] Figure 33 (continued) [Figure 33-07] Figure 33 (continued) [Figure 33-08] Figure 33 (continued) [Figure 33-09] Figure 33 (continued) [Figure 33-10] Figure 33 (continued) [Figure 33-11] Figure 33 (continued) [Figure 33-12] Figure 33 (continued) [Figure 33-13] Figure 33 (continued) [Figure 33-14] Figure 33 (continued) [Figure 33-15] Figure 33 (continued) [Figure 33-16] Figure 33 (continued) [Figure 33-17] Figure 33 (continued) [Figure 33-18] Figure 33 (continued) [Figure 33-19] Figure 33 (continued) [Figure 33-20] Figure 33 (continued) [Figure 33-21] Figure 33 (continued) [Figure 33-22] Figure 33 (continued) [Figure 33-23] Figure 33 (continued) [Figure 33-24] Figure 33 (continued) [Figure 33-25] Figure 33 (continued) [Figure 33-26] Figure 33 (continued) [Figure 34-01] Figure 34 shows nucleic acid sequences encoding exemplary light chain variable regions of the anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the light chain variable regions provided herein. [Figure 34-02] Figure 34 (continued) [Figure 34-03] Figure 34 (continued) [Figure 34-04] Figure 34 (continued) [Figure 34-05] Figure 34 (continued) [Figure 34-06] Figure 34 (continued) [Figure 34-07] Figure 34 (continued) [Figure 34-08] Figure 34 (continued) [Figure 34-09] Figure 34 (continued) [Figure 34-10] Figure 34 (continued) [Figure 34-11] Figure 34 (continued) [Figure 34-12] Figure 34 (continued) [Figure 34-13] Figure 34 (continued) [Figure 34-14] Figure 34 (continued) [Figure 34-15] Figure 34 (continued) [Figure 34-16] Figure 34 (continued) [Figure 34-17] Figure 34 (continued) [Figure 34-18] Figure 34 (continued) [Figure 34-19] Figure 34 (continued) [Figure 34-20] Figure 34 (continued) [Figure 34-21] Figure 34 (continued) [Figure 34-22] Figure 34 (continued) [Figure 34-23] Figure 34 (continued) [Figure 34-24] Figure 34 (continued) [Figure 34-25] Figure 34 (continued) [Figure 34-26] Figure 34 (continued) [Figure 35-01] Figure 35 shows the nucleic acid sequence encoding an exemplary heavy chain of an anti-Gal3 antibody disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy chains provided herein. [Figure 35-02] Figure 35 (continued) [Figure 35-03] Figure 35 (continued) [Figure 35-04] Figure 35 (continued) [Figure 35-05] Figure 35 (continued) [Figure 35-06] Figure 35 (continued) [Figure 35-07] Figure 35 (continued) [Figure 35-08] Figure 35 (continued) [Figure 35-09] Figure 35 (continued) [Figure 35-10] Figure 35 (continued) [Figure 35-11] Figure 35 (continued) [Figure 35-12] Figure 35 (continued) [Figure 35-13] Figure 35 (continued) [Figure 35-14] Figure 35 (continued) [Figure 35-15] Figure 35 (continued) [Figure 35-16] Figure 35 (continued) [Figure 35-17] Figure 35 (continued) [Figure 35-18] Figure 35 (continued) [Figure 35-19] Figure 35 (continued) [Figure 35-20] Figure 35 (continued) [Figure 35-21] Figure 35 (continued) [Figure 35-22] Figure 35 (continued) [Figure 35-23] Figure 35 (continued) [Figure 35-24] Figure 35 (continued) [Figure 35-25] Figure 35 (continued) [Figure 35-26] Figure 35 (continued) [Figure 35-27] Figure 35 (continued) [Figure 35-28] Figure 35 (continued) [Figure 35-29] Figure 35 (continued) [Figure 35-30] Figure 35 (continued) [Figure 35-31] Figure 35 (continued) [Figure 35-32] Figure 35 (continued) [Figure 35-33] Figure 35 (continued) [Figure 35-34] Figure 35 (continued) [Figure 35-35] Figure 35 (continued) [Figure 35-36] Figure 35 (continued) [Figure 35-37] Figure 35 (continued) [Figure 35-38] Figure 35 (continued) [Figure 35-39] Figure 35 (continued) [Figure 35-40] Figure 35 (continued) [Figure 35-41] Figure 35 (continued) [Figure 35-42] Figure 35 (continued) [Figure 35-43] Figure 35 (continued) [Figure 35-44] Figure 35 (continued) [Figure 35-45] Figure 35 (continued) [Figure 35-46] Figure 35 (continued) [Figure 35-47] Figure 35 (continued) [Figure 35-48] Figure 35 (continued) [Figure 35-49] Figure 35 (continued) [Figure 35-50] Figure 35 (continued) [Figure 35-51] Figure 35 (continued) [Figure 35-52] Figure 35 (continued) [Figure 35-53] Figure 35 (continued) [Figure 35-54] Figure 35 (continued) [Figure 35-55] Figure 35 (continued) [Figure 35-56] Figure 35 (continued) [Figure 35-57] Figure 35 (continued) [Figure 35-58] Figure 35 (continued) [Figure 35-59] Figure 35 (continued) [Figure 35-60] Figure 35 (continued) [Figure 35-61] Figure 35 (continued) [Figure 35-62] Figure 35 (continued) [Figure 35-63] Figure 35 (continued) [Figure 35-64] Figure 35 (continued) [Figure 35-65] Figure 35 (continued) [Figure 35-66]Figure 35 (continued) [Figure 35-67] Figure 35 (continued) [Figure 35-68] Figure 35 (continued) [Figure 35-69] Figure 35 (continued) [Figure 35-70] Figure 35 (continued) [Figure 35-71] Figure 35 (continued) [Figure 35-72] Figure 35 (continued) [Figure 35-73] Figure 35 (continued) [Figure 36-01] Figure 36 shows the nucleic acid sequence encoding an exemplary light chain of an anti-Gal3 antibody disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the light chains provided herein. [Figure 36-02] Figure 36 (continued) [Figure 36-03] Figure 36 (continued) [Figure 36-04] Figure 36 (continued) [Figure 36-05] Figure 36 (continued) [Figure 36-06] Figure 36 (continued) [Figure 36-07] Figure 36 (continued) [Figure 36-08] Figure 36 (continued) [Figure 36-09] Figure 36 (continued) [Figure 36-10] Figure 36 (continued) [Figure 36-11] Figure 36 (continued) [Figure 36-12] Figure 36 (continued) [Figure 36-13] Figure 36 (continued) [Figure 36-14] Figure 36 (continued) [Figure 36-15] Figure 36 (continued) [Figure 36-16] Figure 36 (continued) [Figure 36-17] Figure 36 (continued) [Figure 36-18] Figure 36 (continued) [Figure 36-19] Figure 36 (continued) [Figure 36-20]Figure 36 (continued) [Figure 36-21] Figure 36 (continued) [Figure 36-22] Figure 36 (continued) [Figure 36-23] Figure 36 (continued) [Figure 36-24] Figure 36 (continued) [Figure 36-25] Figure 36 (continued) [Figure 36-26] Figure 36 (continued) [Figure 36-27] Figure 36 (continued) [Figure 36-28] Figure 36 (continued) [Figure 36-29] Figure 36 (continued) [Figure 36-30] Figure 36 (continued) [Figure 36-31] Figure 36 (continued) [Figure 36-32] Figure 36 (continued) [Figure 36-33] Figure 36 (continued) [Figure 36-34] Figure 36 (continued) [Figure 36-35] Figure 36 (continued) [Figure 36-36] Figure 36 (continued) [Figure 36-37] Figure 36 (continued) [Figure 37A] 37A-37B show an exemplary alignment of the heavy chain CDRs (FIG. 37A) and light chain CDRs (FIG. 37B) of an exemplary anti-Gal3 antibody disclosed herein. [Figure 37B] 37A-37B show an exemplary alignment of the heavy chain CDRs (FIG. 37A) and light chain CDRs (FIG. 37B) of an exemplary anti-Gal3 antibody disclosed herein. [Figure 38A] 38A-38D each show a table containing a subset of the anti-Gal3 antibodies disclosed herein. In some embodiments, sequences containing heavy chain variable region CDRs, light chain variable region CDRs, heavy chain variable regions, light chain variable regions, heavy chains, and light chains, or combinations thereof, can be selected from any one or more of the anti-Gal3 antibodies provided as subsets in each table. [Figure 38B]38A-38D each show a table containing a subset of the anti-Gal3 antibodies disclosed herein. In some embodiments, sequences containing heavy chain variable region CDRs, light chain variable region CDRs, heavy chain variable regions, light chain variable regions, heavy chains, and light chains, or combinations thereof, can be selected from any one or more of the anti-Gal3 antibodies provided as subsets in each table. [Figure 38C] 38A-38D each show a table containing a subset of the anti-Gal3 antibodies disclosed herein. In some embodiments, sequences containing heavy chain variable region CDRs, light chain variable region CDRs, heavy chain variable regions, light chain variable regions, heavy chains, and light chains, or combinations thereof, can be selected from any one or more of the anti-Gal3 antibodies provided as subsets in each table. [Figure 38D] 38A-38D each show a table containing a subset of the anti-Gal3 antibodies disclosed herein. In some embodiments, sequences containing heavy chain variable region CDRs, light chain variable region CDRs, heavy chain variable regions, light chain variable regions, heavy chains, and light chains, or combinations thereof, can be selected from any one or more of the anti-Gal3 antibodies provided as subsets in each table. [Figure 39A] 39A-39E each show a table containing a subset of the anti-Gal3 antibodies disclosed herein. In some embodiments, sequences containing heavy chain variable region CDRs, light chain variable region CDRs, heavy chain variable regions, light chain variable regions, heavy chains, and light chains, or combinations thereof, can be selected from any one or more of the anti-Gal3 antibodies provided as subsets in each table. [Figure 39B] 39A-39E each show a table containing a subset of the anti-Gal3 antibodies disclosed herein. In some embodiments, sequences containing heavy chain variable region CDRs, light chain variable region CDRs, heavy chain variable regions, light chain variable regions, heavy chains, and light chains, or combinations thereof, can be selected from any one or more of the anti-Gal3 antibodies provided as subsets in each table. [Figure 39C]39A-39E each show a table containing a subset of the anti-Gal3 antibodies disclosed herein. In some embodiments, sequences containing heavy chain variable region CDRs, light chain variable region CDRs, heavy chain variable regions, light chain variable regions, heavy chains, and light chains, or combinations thereof, can be selected from any one or more of the anti-Gal3 antibodies provided as subsets in each table. [Figure 39D] 39A-39E each show a table containing a subset of the anti-Gal3 antibodies disclosed herein. In some embodiments, sequences containing heavy chain variable region CDRs, light chain variable region CDRs, heavy chain variable regions, light chain variable regions, heavy chains, and light chains, or combinations thereof, can be selected from any one or more of the anti-Gal3 antibodies provided as subsets in each table. [Figure 39E] 39A-39E each show a table containing a subset of the anti-Gal3 antibodies disclosed herein. In some embodiments, sequences containing heavy chain variable region CDRs, light chain variable region CDRs, heavy chain variable regions, light chain variable regions, heavy chains, and light chains, or combinations thereof, can be selected from any one or more of the anti-Gal3 antibodies provided as subsets in each table. [Figure 40A] Figures 40A-C show quantification of the affinity (KD) for human Gal3 of TB006 (Figure 40A), TB006 (Figure 40B), and the control antibody Synagis (Figure 40C). [Figure 40B] Figures 40A-C show quantification of the affinity (KD) for human Gal3 of TB006 (Figure 40A), TB006 (Figure 40B), and the control antibody Synagis (Figure 40C). [Figure 40C] Figures 40A-C show quantification of the affinity (KD) for human Gal3 of TB006 (Figure 40A), TB006 (Figure 40B), and the control antibody Synagis (Figure 40C). [Figure 41A]Figures 41A-C show quantification of the affinity (KD) for mouse Gal3 of TB006 (Figure 41A), TB006 (Figure 41B), and the control antibody Synagis (Figure 41C). [Figure 41B] Figures 41A-C show quantification of the affinity (KD) for mouse Gal3 of TB006 (Figure 41A), TB006 (Figure 41B), and the control antibody Synagis (Figure 41C). [Figure 41C] Figures 41A-C show quantification of the affinity (KD) for mouse Gal3 of TB006 (Figure 41A), TB006 (Figure 41B), and the control antibody Synagis (Figure 41C). [Figure 42A] Figures 42A-B show quantification of the affinity (KD) of TB006 (Figure 42A, left panel), TB001 (Figure 42B, right panel), and the control antibody Synagis (Figure 42B) for cynomolgus Gal3. [Figure 42B] Figures 42A-B show quantification of the affinity (KD) of TB006 (Figure 42A, left panel), TB001 (Figure 42B, right panel), and the control antibody Synagis (Figure 42B) for cynomolgus Gal3. [Figure 43A] Figures 43A-C show quantification of the affinity (KD) for rat Gal3 of TB006 (Figure 43A), TB001 (Figure 43B), and the control antibody Synagis (Figure 43C). [Figure 43B] Figures 43A-C show quantification of the affinity (KD) for rat Gal3 of TB006 (Figure 43A), TB001 (Figure 43B), and the control antibody Synagis (Figure 43C). [Figure 43C] Figures 43A-C show quantification of the affinity (KD) for rat Gal3 of TB006 (Figure 43A), TB001 (Figure 43B), and the control antibody Synagis (Figure 43C). [Figure 44A]Figures 44A-44E show quantification of insulin-independent GLUT4 translocation mediated by Gal3 complexed with exemplary anti-Gal3 antibodies TB006 (Figure 44A), 2D10 variant (Figure 44B), 20H5 variant (Figure 44C), 21H6 variant (Figure 44D), and other exemplary anti-Gal3 antibodies disclosed herein (Figure 44E). [Figure 44B] Figures 44A-44E show quantification of insulin-independent GLUT4 translocation mediated by Gal3 complexed with exemplary anti-Gal3 antibodies TB006 (Figure 44A), 2D10 variant (Figure 44B), 20H5 variant (Figure 44C), 21H6 variant (Figure 44D), and other exemplary anti-Gal3 antibodies disclosed herein (Figure 44E). [Figure 44C] Figures 44A-44E show quantification of insulin-independent GLUT4 translocation mediated by Gal3 complexed with exemplary anti-Gal3 antibodies TB006 (Figure 44A), 2D10 variant (Figure 44B), 20H5 variant (Figure 44C), 21H6 variant (Figure 44D), and other exemplary anti-Gal3 antibodies disclosed herein (Figure 44E). [Figure 44D] Figures 44A-44E show quantification of insulin-independent GLUT4 translocation mediated by Gal3 complexed with exemplary anti-Gal3 antibodies TB006 (Figure 44A), 2D10 variant (Figure 44B), 20H5 variant (Figure 44C), 21H6 variant (Figure 44D), and other exemplary anti-Gal3 antibodies disclosed herein (Figure 44E). [Figure 44E] Figures 44A-44E show quantification of insulin-independent GLUT4 translocation mediated by Gal3 complexed with exemplary anti-Gal3 antibodies TB006 (Figure 44A), 2D10 variant (Figure 44B), 20H5 variant (Figure 44C), 21H6 variant (Figure 44D), and other exemplary anti-Gal3 antibodies disclosed herein (Figure 44E). [Figure 45]FIG. 45 shows the quantification of insulin-independent GLUT4 translocation mediated by various Gal3 variants complexed with an exemplary anti-Gal3 antibody, TB006. [Figure 46A] Figures 46A-46D show quantification of Gal3 binding to GLUT1 or GLUT4 by ELISA (Figure 46A), and the ability of exemplary anti-Gal3 antibodies TB006 and 2D10-VH0-VL0 to disrupt Gal3 binding to GLUT1 (Figure 46B) or GLUT4 (Figure 46C). Figure 46D shows the IC50 of antibody-mediated disruption of Gal3 binding to GLUT1 or GLUT4 measured in Figures 46B-46C. [Figure 46B] Figures 46A-46D show quantification of Gal3 binding to GLUT1 or GLUT4 by ELISA (Figure 46A), and the ability of exemplary anti-Gal3 antibodies TB006 and 2D10-VH0-VL0 to disrupt Gal3 binding to GLUT1 (Figure 46B) or GLUT4 (Figure 46C). Figure 46D shows the IC50 of antibody-mediated disruption of Gal3 binding to GLUT1 or GLUT4 measured in Figures 46B-46C. [Figure 46C] Figures 46A-46D show quantification of Gal3 binding to GLUT1 or GLUT4 by ELISA (Figure 46A), and the ability of exemplary anti-Gal3 antibodies TB006 and 2D10-VH0-VL0 to disrupt Gal3 binding to GLUT1 (Figure 46B) or GLUT4 (Figure 46C). Figure 46D shows the IC50 of antibody-mediated disruption of Gal3 binding to GLUT1 or GLUT4 measured in Figures 46B-46C. [Figure 46D]Figures 46A-46D show quantification of Gal3 binding to GLUT1 or GLUT4 by ELISA (Figure 46A), and the ability of exemplary anti-Gal3 antibodies TB006 and 2D10-VH0-VL0 to disrupt Gal3 binding to GLUT1 (Figure 46B) or GLUT4 (Figure 46C). Figure 46D shows the IC50 of antibody-mediated disruption of Gal3 binding to GLUT1 or GLUT4 measured in Figures 46B-46C. [Figure 47] Figure 47 shows a hydrogen-deuterium mass spectrometry heat map of hGal3 complexed with GLUT4, indicating the putative regions of Gal3 involved in binding to GLUT4. Darker regions on the heat map indicate less deuterium uptake after binding. [Figure 48] Figure 48 shows fluorescence microscopy images of L6 myoblasts treated with exemplary anti-Gal3 antibodies TB006 or 2D10, with or without Gal3, demonstrating that these anti-Gal3 antibodies are internalized into myoblasts only in the presence of Gal3. [Figure 49A] Figures 49A-B show quantification of Gal3-mediated inhibition of glucose tolerance by co-treatment with anti-Gal3 antibody in vivo. Figure 49A shows an exemplary schematic of this study. Figure 49B shows a time series of glucose levels in blood samples taken after administration of Gal3 ± exemplary anti-Gal3 antibody TB001 followed by glucose administration. Mice injected with Gal3 alone showed increased blood glucose levels, while mice injected with a mixture of Gal3 and anti-Gal3 antibody showed blood glucose levels similar to those of PBS-injected control mice. [Figure 49B]Figures 49A-B show quantification of Gal3-mediated inhibition of glucose tolerance by co-treatment with anti-Gal3 antibody in vivo. Figure 49A shows an exemplary schematic of this study. Figure 49B shows a time series of glucose levels in blood samples taken after administration of Gal3 ± exemplary anti-Gal3 antibody TB001 followed by glucose administration. Mice injected with Gal3 alone showed increased blood glucose levels, while mice injected with a mixture of Gal3 and anti-Gal3 antibody showed blood glucose levels similar to those of PBS-injected control mice. DETAILED DESCRIPTION OF THE INVENTION

[0017] Diabetes mellitus is a group of metabolic diseases characterized by prolonged high blood glucose levels. There are three main types of diabetes mellitus: type I diabetes, type II diabetes, and gestational diabetes. Type I diabetes is caused by the inability of the pancreas to produce enough insulin due to a decrease in insulin-producing beta cells. Type II diabetes is characterized by insulin resistance and can be due to a variety of lifestyle, dietary, and genetic factors, including obesity, poor diet, and stress. Gestational diabetes occurs when pregnant women with no prior history of diabetes develop high blood glucose levels.

[0018] In addition to diabetes, insulin resistance is associated with other diseases. Insulin resistance occurs when a subject's cells become less sensitive to insulin, leading to the pancreas secreting more insulin. If the pancreas cannot produce enough insulin to maintain safe blood glucose levels, the subject can progress to prediabetes and diabetes. Hyperinsulinemia (abnormally high blood insulin levels) may also occur. Insulin resistance is also responsible for other diseases, including metabolic syndrome, type A insulin resistance, type B insulin resistance, acanthosis nigricans, and polycystic ovary syndrome (PCOS). Obesity and cardiovascular disease are also associated with insulin resistance and prediabetes / diabetes.

[0019] Galectin-3 (Gal3, GAL3) is known to play important roles in cell proliferation, adhesion, differentiation, angiogenesis, and apoptosis. This activity is due, at least in part, to its immunomodulatory properties and binding affinity for other immunomodulatory proteins, signaling proteins, and other cell surface markers. Gal3 functions through distinct N- and C-terminal domains. The N-terminal domain (isoform 1: amino acids 1-111; isoform 3: amino acids 1-125) contains a tandem repeat domain (TRD; isoform 1: amino acids 36-109; isoform 3: amino acids 50-123) and is primarily involved in Gal3 oligomerization. The C-terminal domain (isoform 1: amino acids 112-250; isoform 3: amino acids 126-264) contains a carbohydrate recognition and binding domain (CRD) that binds to β-galactosides. An exemplary sequence of human Gal3 isoform 1 (NCBI reference number NP_002297.2) is shown in SEQ ID NO: 1. An exemplary sequence of isoform 3 of human Gal3 (NCBI reference number NP_001344607.1) is shown in SEQ ID NO:2.

[0020] Furthermore, Gal3 has been shown to be elevated in obese humans and is thought to cause insulin resistance and glucose intolerance in these subjects. Gal3 has been shown to directly bind to the insulin receptor and inhibit downstream signaling. Thus, Gal3 may contribute to obesity-induced insulin resistance and chronic tissue inflammation.

[0021] In some embodiments, an anti-Gal3 antibody or binding fragment thereof, or a composition comprising an anti-Gal3 antibody or binding fragment thereof, is provided. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the N-terminal domain, N-terminus, and / or TRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the C-terminal domain, C-terminus, and / or CRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the N-terminal domain, N-terminus, and / or TRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the C-terminal domain, C-terminus, and / or CRD of Gal3.

[0022] In some embodiments provided herein, Gal3 has been shown to inhibit glucose transporter (GLUT) translocation in living cells. In some embodiments, the glucose transporter is GLUT1 and / or GLUT4. This inhibition can result in insulin resistance, leading to diseases or disorders associated with insulin resistance.

[0023] Disclosed herein, in some embodiments, are methods for enhancing GLUT translocation in cells by contacting the cells with an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks or disrupts the interaction between Gal3 and GLUT or another protein associated with GLUT translocation. In some embodiments, the GLUT is GLUT1 and / or GLUT4. This contacting can be performed in vitro or in vivo.

[0024] Also disclosed herein, in some embodiments, is a method for enhancing GLUT translocation in a cell by contacting the cell with a preincubated complex of Gal3 with an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the GLUT is GLUT1 and / or GLUT4. This contacting can be performed in vitro or in vivo.

[0025] Also disclosed herein, in some embodiments, are methods for improving insulin sensitivity in a subject in need thereof by administering an anti-Gal3 antibody or binding fragment thereof to the subject. In some embodiments, the anti-Gal3 antibody or binding fragment thereof improves insulin sensitivity in the subject by blocking or disrupting the interaction between Gal3 and GLUT or another protein associated with GLUT translocation. In some embodiments, the GLUT is GLUT1 and / or GLUT4.

[0026] Also disclosed herein, in some embodiments, is a method for improving insulin sensitivity in a subject in need thereof by administering to the subject a complex preincubated with Gal3 and an anti-Gal3 antibody or binding fragment thereof, whereby the GLUT is GLUT1 and / or GLUT4.

[0027] Also disclosed herein, in some embodiments, are methods for treating a disease associated with insulin resistance in a subject in need thereof by administering to the subject an anti-Gal3 antibody or binding fragment thereof, thereby treating the disease associated with insulin resistance in the subject. In some embodiments, the disease associated with insulin resistance comprises diabetes mellitus, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is administered to the subject. Administering a segment thereof to a subject treats the disease or insulin resistance associated with the disease. In some embodiments, the method comprises administering any antibody or variant thereof as provided herein in a therapeutically effective amount sufficient to interfere with the interaction between GAL3 and GLUT (e.g., GLUT1 and / or GLUT4) to treat (depending on the subject having and / or reducing the risk of) one or more of diabetes mellitus, insulin resistance, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer.

[0028] Also disclosed herein, in some embodiments, are methods for treating a disease associated with insulin resistance in a subject in need thereof by administering to the subject a complex preincubated with Gal3 and an anti-Gal3 antibody or binding fragment thereof, thereby treating the disease in the subject. In some embodiments, the disease associated with insulin resistance includes diabetes mellitus, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer. In some embodiments, the disease, or insulin resistance associated with the disease, is treated by administering to the subject an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the method comprises administering any antibody or variant thereof as provided herein in a therapeutically effective amount sufficient to interfere with the interaction between GAL3 and GLUT (e.g., GLUT1 and / or GLUT4) to treat (depending on the subject having and / or reducing the risk of) one or more of diabetes mellitus, insulin resistance, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer.

[0029] In some embodiments, administration of any one of the anti-Gal3 antibodies or binding fragments thereof disclosed herein can reduce insulin resistance in a subject.

[0030] definition In the following detailed description, reference is made to the accompanying drawings, which also form a part of this specification. In these drawings, like symbols generally identify like components unless context dictates otherwise. The illustrative embodiments set forth in the detailed description, drawings, and claims are not intended to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit and scope of the inventive subject matter presented herein. It will be readily understood that aspects of the present disclosure, while generally described herein and illustrated in the figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are expressly contemplated herein.

[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter belongs. It is to be understood that the foregoing summary and the following detailed description are exemplary and explanatory only and are not restrictive of the claimed subject matter.

[0032] The section headings used herein are for organizational purposes only and do not limit the subject matter described. should not be construed as

[0033] In this application, the use of the singular includes the plural unless specifically stated otherwise. It should be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include the plural unless the context clearly dictates otherwise. In this application, the use of "or" means "and / or" unless specifically stated otherwise. Furthermore, the use of the term "including," as well as other word forms such as "include," "includes," and "included," is non-limiting.

[0034] "About" means an amount, level, value, number, frequency, proportion, dimension, size, content, weight, or length that varies by about 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% from a reference amount, level, value, number, frequency, proportion, dimension, size, content, weight, or length.

[0035] As used herein, unless the context requires otherwise, the terms "comprise," "comprises," and "comprising" should be understood to refer to the inclusion of the stated step or element or steps or elements, and not to the exclusion of any other step or element or steps or elements. "Consisting of" means inclusive of and limited to what follows the phrase "consisting of." That is, the phrase "consisting of" indicates that the recited elements are required, i.e., essential, and that no other elements may be present. "Consisting essentially of" means including the recited elements following the phrase, and is limited to other elements that do not interfere with or contribute to the activity or function specified in this disclosure for the recited elements. That is, the phrase "consisting essentially of" indicates that the recited elements are required, i.e., essential, but that other elements are optional and may or may not be present depending on whether they substantially affect the activity or function of the recited elements.

[0036] As used herein, the terms "individual," "subject," and "patient" refer to any mammal. In some embodiments, the mammal is a human. In some embodiments, the mammal is non-human. None of the above terms require or are limited to situations characterized by the supervision (e.g., constant or intermittent supervision) of a health care professional (e.g., a physician, registered nurse, nurse practitioner, physician assistant, orderly, or hospice worker).

[0037] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length, which may be linear, cyclic, or branched, may contain modified amino acids, or may be interrupted by non-amino acids. These terms also encompass amino acid polymers that have been modified, for example, by sulfation, glycosylation, lipidation, acetylation, phosphorylation, iodination, methylation, oxidation, protein processing, phosphorylation, prenylation, racemization, selenoylation, transfer-RNA-mediated addition of amino acids to proteins such as arginylation, ubiquitination, or any other manipulation, such as conjugation with a labeling component.

[0038] As used herein, the term "amino acid" refers to natural and / or unnatural or synthetic amino acids, including glycine and both the D- and L-optical isomers, as well as amino acid analogs and peptidomimetics.

[0039] A polypeptide or amino acid sequence "derived from" a specified protein refers to the origin of the polypeptide. Preferably, the polypeptide has an amino acid sequence that is essentially identical to, or immunologically identifiable by, the amino acid sequence of a polypeptide encoded by the sequence, or a portion thereof consisting of at least 10-20 amino acids, or at least 20-30 amino acids, or at least 30-50 amino acids. The term also encompasses polypeptides expressed from a specified nucleic acid sequence.

[0040] As used herein, the term "antibody" has the meaning ascribed to it by one of skill in the art and is further intended to encompass any polypeptide chain-containing molecular structure having a specific shape that fits and recognizes an epitope, where one or more non-covalent interactions stabilize the complex between the molecular structure and the epitope. Antibodies may be polyclonal, although monoclonal antibodies may be preferred because they can be reproduced in cell culture or recombinantly and can be modified to reduce their antigenicity.

[0041] In addition to whole immunoglobulins (or their recombinant counterparts), immunoglobulin fragments or "binding fragments" containing epitope-binding sites (e.g., Fab', F(ab')2, single-chain variable region fragments (scFv), diabodies, minibodies, nanobodies, single-domain antibodies (sdAb), or other fragments) are useful as antibody portions in the present invention. Such antibody fragments can be generated from whole immunoglobulins by protease cleavage with ricin, pepsin, papain, etc. Minimal immunoglobulins can be engineered using recombinant immunoglobulin technology. For example, "Fv" immunoglobulins for use in the present invention can be generated by linking the light chain variable region to the heavy chain variable region via a peptide linker (e.g., polyglycine or another sequence that does not form an α-helical or β-sheet motif). Nanobodies or single-domain antibodies can also be obtained from other animals, such as dromedaries, camels, llamas, alpacas, or sharks. In some embodiments, the antibody can be a conjugate, such as a pegylated antibody, a drug conjugate, a radioisotope conjugate, or a toxin conjugate. Monoclonal antibodies directed to a specific epitope or combination of epitopes allow for targeting and / or depletion of cell populations expressing the marker. A variety of techniques using monoclonal antibodies to screen cell populations expressing markers are available, including magnetic separation using antibody-coated magnetic beads, "panning" with antibodies attached to a solid matrix (i.e., plate), and flow cytometry (e.g., U.S. Pat. No. 5,985,660, expressly incorporated herein by reference in its entirety).

[0042] As known in the art, the term "Fc region" is used to define the C-terminal region of an immunoglobulin heavy chain. This "Fc region" may be a native-sequence Fc region or a variant Fc region. Although the boundaries of the Fc region of an immunoglobulin heavy chain may vary, the Fc region of a human IgG heavy chain is usually defined to stretch from the amino acid residue at position Cys226 or from the amino acid residue at position Pro230 to the carboxyl terminus. The numbering of residues within the Fc region is that of the EU index as in Kabat. Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991. The Fc region of an immunoglobulin usually consists of two constant domains, CH2 and CH3. As known in the art, the Fc region may exist in a dimeric or monomeric form.

[0043] As known in the art, a "constant region" of an antibody refers to the constant region of the antibody light chain or the constant region of the antibody heavy chain, either alone or in combination.

[0044] The "variable region" of an antibody refers to the variable region of the antibody light chain or the variable region of the antibody heavy chain, either alone or in combination. As is known in the art, the variable regions of the heavy and light chains each consist of four framework regions (FRs) connected by three complementarity-determining regions (CDRs), also known as hypervariable regions, which contribute to the formation of the antigen-binding site of the antibody. When a variant of a target variable region is desired, particularly a variant with a substitution of an amino acid residue outside the CDR region (i.e., within the framework region), appropriate amino acid substitutions, preferably conservative amino acid substitutions, can be identified by comparing the target variable region with the variable regions of other antibodies in the same canonical class as the target variable region and containing the CDR1 and CDR2 sequences (Chothia and Lesk, J Mol Biol 196(4): 901-917, 1987).

[0045] In some embodiments, delineation of CDRs and identification of the residues that comprise the antibody binding site are achieved by analyzing the structure of the antibody and / or the structure of an antibody-ligand complex. In some embodiments, this can be achieved by any of a variety of techniques known to those of skill in the art, such as X-ray crystallography. In some embodiments, various analytical methods can be employed to identify or estimate CDR regions. Examples of such methods include, but are not limited to, Kabat definition, Chothia definition, the IMGT approach (Lefranc et al., 2003) Dev Comp Immunol. 27:55-77), computational programs such as Paratome (Kunik et al., 2012, Nucl Acids Res. W521-4), AbM definition, and conformational definition.

[0046] The Kabat definition is a standard for numbering residues within antibodies and is typically used to identify CDR regions. See, e.g., Johnson & Wu, 2000, Nucleic Acids Res., 28: 214-8. The Chothia definition is similar to the Kabat definition, but takes into account the location of certain loop structural regions. See, e.g., Chothia et al., 1986, J. Mol. Biol., 196: 901-17; Chothia et al., 1989, Nature, 342: 877-83. The AbM method of definition uses an integrated suite of computer programs for modeling antibody structure produced by Oxford Molecular Group. See, e.g., Martin et al., 1989, Proc Natl Acad Sci (USA), 86:9268-9272; "AbM.TM., A Computer Program for Modeling Variable Regions of Antibodies," Oxford, UK; Oxford Molecular, Ltd. The AbM method is defined by Samudrala et al., 1999, "Ab Initio The tertiary structure of antibodies is modeled from the primary sequence using a combination of knowledge databases and ab initio methods, such as that described by MacCallum et al., 1996, J. Mol. Biol., 5:194-198, “Protein Structure Prediction Using a Combined Hierarchical Approach.” The contact method definition is based on the analysis of available complex crystal structures. See, for example, MacCallum et al., 1996, J. Mol. Biol., 5:194-198. See, e.g., Makabe et al., 2008, Journal of Biological Chemistry, 283:1156-1166. In another approach, referred to herein as "conformational definition" of CDRs, each CDR position can be considered as a residue that contributes enthalpicly to antigen binding. See, e.g., Makabe et al., 2008, Journal of Biological Chemistry, 283:1156-1166. Still other CDR boundary definitions may not strictly adhere to any of the above approaches, but will overlap with at least a portion of the Kabat CDRs, which can be shortened or lengthened in light of predictions or experimental findings that certain residues or groups of residues do not significantly affect antigen binding. As used herein, CDRs can refer to CDRs defined by any approach known in the art, including a combination of approaches. The methods used herein can utilize CDRs defined according to any of these approaches. In any given embodiment comprising two or more CDRs, the CDRs may be defined according to any of the Kabat, Chothia, Extended, IMGT, Paratome, AbM, and / or conformational definitions, or any combination of the above.

[0047] As disclosed herein, sequences having a certain % identity to any of the sequences disclosed herein are contemplated and may be used. The term "% identity" refers to the percentage of identical units (i.e., amino acids or nucleotides) between two or more sequences relative to the length of the sequences. If two or more sequences being compared are the same length, the % identity is for each length. If two or more sequences being compared are different lengths, deletions and / or insertions may be introduced to achieve the best alignment. In some embodiments, these sequences may include peptide sequences, nucleic acid sequences, CDR sequences, variable region sequences, or heavy or light chain sequences. In some embodiments, any sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any of the sequences disclosed herein may be used. In some embodiments, any sequence having at least 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 substitutions, deletions, or additions to any of the sequences disclosed herein can be used. Changes in sequence can apply to, for example, single amino acids, single nucleic acid bases, or nucleic acid codons, although differences in longer contiguous sequences are also contemplated. When applied to antibody sequences, these differences in sequence can apply to antigen-binding regions (e.g., CDRs) or to regions that do not bind to antigen or are only secondary to antigen binding (e.g., framework regions).

[0048] As disclosed herein, sequences having a certain percent homology to any of the sequences disclosed herein are contemplated and may be used. The term "% homology" refers to the degree of conservation between two sequences when considering three-dimensional structure. For example, homology between two protein sequences may depend on structural motifs such as β-strands, α-helices, and other folds, and their distribution in the sequences. Homology may be determined experimentally or in silico through structural determination. In some embodiments, any sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology to any of the sequences disclosed herein may be used. In some embodiments, there are at least 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, Any sequence with 6, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 substitutions, deletions, or additions can be used.

[0049] As applied herein, sequences having a certain percent similarity to any of the sequences disclosed herein are contemplated and may be used. In some embodiments, these sequences may include peptide sequences, nucleic acid sequences, CDR sequences, variable region sequences, or heavy or light chain sequences. As understood in the art with respect to peptide sequences, "similarity" refers to a comparison of amino acids based on their properties, including but not limited to, size, polarity, charge, pK, aromaticity, hydrogen-bonding properties, or the presence of functional groups (e.g., hydroxyl, thiol, amine, carboxyl, etc.). The term "% similarity" refers to the percentage of identical units (i.e., amino acids) between two or more sequences relative to the length of the sequences. If two or more sequences being compared are the same length, the percent similarity will be the respective lengths. If two or more sequences being compared are different lengths, deletions and / or insertions may be introduced to achieve the best alignment. The similarity of two amino acids may dictate whether a particular substitution is conservative or non-conservative. Methods for determining the conservatism of amino acid substitutions are commonly known in the art and may include substitution matrices. Commonly used substitution matrices include BLOSUM45, BLOSUM62, BLOSUM80, PAM100, PAM120, PAM160, PAM200, and PAM250, although other substitution matrices or approaches may be used if deemed appropriate by those of skill in the art. Certain substitution matrices may be preferred over others when considering aspects such as stringency, conservation, and / or divergence of related sequences (e.g., within a species or more broadly), as well as the length of the sequences. As used herein, a peptide sequence having a certain percent similarity to another sequence has up to that many amino acids that are identical or that are permissible substitutions, depending on the method of determining similarity used.In some embodiments, sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to any of the sequences disclosed herein may be used. In some embodiments, any sequence having at least 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 similar substitutions relative to any of the sequences disclosed herein can be used. When applied to antibody sequences, these similar substitutions can be applied to antigen-binding regions (i.e., CDRs) or to regions that do not bind antigen or are only secondary to antigen binding (i.e., framework regions).

[0050] The term "consensus sequence," as used herein with respect to sequences, refers to a generalized sequence that represents all of the various combinations of allowable amino acids at each position in a group of sequences. Consensus sequences provide insight into conserved regions of related sequences, where units (e.g., amino acids or nucleotides) are the same throughout most or all of the sequence, and regions that show differences between the sequences. In the case of antibodies, consensus sequences for CDRs may represent amino acids that are important or unnecessary for antigen binding. While a consensus sequence can be generated using any of the sequences provided herein, it is contemplated that various sequences derived from this consensus sequence can be verified to have similar effects as the template sequence.

[0051] As used herein with respect to antibodies, the term "compete" refers to a first "Cross-competition" means that a first antibody, or antigen-binding portion thereof, binds to an epitope in a manner sufficiently similar to that of a second antibody, or antigen-binding portion thereof, such that the binding of the antibody to its cognate epitope is detectably reduced in the presence of the second antibody, compared to binding of the first antibody in the absence of the second antibody. Alternatively, but not necessarily, binding of the second antibody to its epitope is detectably reduced in the presence of the first antibody. That is, the first antibody can inhibit binding of the second antibody to its epitope, and the second antibody does not inhibit binding of the first antibody to its respective epitope. However, if each detectably inhibits binding of the other antibody to its cognate epitope or cognate ligand, whether to the same extent, a greater extent, or a lesser extent, these antibodies are said to "cross-compete" with each other for binding of their respective epitopes. Both competing and cross-competing antibodies are encompassed by the present invention. Regardless of the mechanism by which such competition or cross-competition occurs (e.g., steric hindrance, conformational change, or binding to a common epitope or portion thereof), one of skill in the art will understand, based on the teachings provided herein, that such competing and / or cross-competing antibodies are encompassed and may be useful in the methods disclosed herein.

[0052] The terms "preferentially bind" or "specifically bind" (used interchangeably herein) by an antibody to an epitope are well understood in the art, and methods for determining such specific or preferential binding are also well known in the art. A molecule is said to exhibit "specific binding" or "preferential binding" if it reacts or binds to a particular cell or substance more frequently, and / or more rapidly, and / or for a longer duration, and / or with greater affinity than it reacts or binds to another cell or substance. An antibody "specifically binds" or "preferentially binds" to a target if it binds with greater affinity, and / or with greater avidity, and / or more rapidly and / or for a longer duration than it binds to other substances. For example, an antibody that specifically or preferentially binds to a target epitope is one that binds to that epitope with greater affinity and / or avidity, and / or more readily and / or for a longer duration, than it binds to other target epitopes or non-target epitopes. It is understood by reading this definition that, for example, an antibody (or moiety or epitope) that specifically or preferentially binds to a first target may or may not specifically or preferentially bind to a second target. Thus, "specific binding" or "preferential binding" does not necessarily require (although it can include) exclusive binding. Usually, but not necessarily, references to binding refer to preferential binding.

[0053] The terms "block" or "disrupt," as used herein with respect to antibodies, refer to the ability of an antibody to interfere with a biological process, including, but not limited to, the activity of an enzyme, the binding of two or more biomolecules (e.g., two or more proteins, peptides, nucleic acids, lipids, etc.), or the progression of a signaling cascade. Generally, the interference with a biological process involves the antibody binding to its target or an epitope thereof, thereby interfering with the normal function of the target, such as blocking the active site of the target, blocking another region of the target that is important for the function of the target, or altering the localization and / or trafficking of the target. The blocking or disrupting activity of an antibody may be quantified in terms of a reduction in the biological process relative to a control condition in which the biological process is not disrupted. In other cases, the blocking or disrupting activity of an antibody may be quantified in terms of modulation, whether direct or inverse, in another biological process known to be associated with the target biological process. In some embodiments, the blocking or disrupting activity is at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 120%, 140%, 160%, 180%, 190%, 210%, 220%, 230%, 240%, 250%, 260%, 280%, 290%, 300%, 410%, 420%, 430%, 440%, 450%, 460%, 480%, 490%, 500%, 510%, 520%, 530%, 540%, 550%, 560%, 570%, 580%, 590%, 600%, 610%, 620%, 630%, 640%, 650%, 660%, 670%, 680%, The anti-Gal3 antibody may cause a change of 0%, 50%, 60%, 70%, 80%, 90%, or 100%, or any percentage within a range defined by any two of the above values. In some embodiments provided herein, the interaction between Gal3 and GLUT (e.g., GLUT1 and / or GLUT4) is a biological process that can be disrupted by an anti-Gal3 antibody. The interaction between Gal3 and GLUT may or may not be a direct interaction between Gal3 and GLUT, and it is contemplated that the anti-Gal3 antibody may interfere with some other aspect of the activity of Gal3 and / or GLUT.

[0054] As used herein, the term "antigen-binding molecule" refers to a molecule comprising an antigen-binding portion that binds to an antigen and, optionally, a scaffold or framework portion that enables the antigen-binding portion to adopt a conformation that promotes binding of the antigen-binding portion or that confers some additional property to the antigen-binding molecule. In some embodiments, the antigen is Gal3. In some embodiments, the antigen-binding portion comprises at least one CDR from an antibody that binds to the antigen. In some embodiments, the antigen-binding portion comprises all three CDRs from the heavy chain of an antibody that binds to the antigen, or all three CDRs from the light chain of an antibody that binds to the antigen. In some embodiments, the antigen-binding portion comprises all six CDRs (three from the heavy chain and three from the light chain) from an antibody that binds to the antigen. In some embodiments, the antigen-binding portion is an antibody fragment.

[0055] Non-limiting examples of antigen-binding molecules include antibodies, antibody fragments (e.g., antigen-binding fragments of antibodies), antibody derivatives, and antibody analogs. Further specific examples include, but are not limited to, single-chain variable region fragments (scFv), nanobodies (e.g., VH domains of camelid heavy chain antibodies; VHH fragments, see Cortez-Retamozo et al., Cancer Research, Vol. 64:2853-57, 2004), Fab fragments, Fab' fragments, F(ab')2 fragments, Fv fragments, Fd fragments, and complementarity-determining region (CDR) fragments. These molecules can be obtained from any mammalian source, such as human, mouse, rat, rabbit, pig, dog, cat, horse, donkey, guinea pig, goat, or camelid. Antibody fragments may compete for the binding of a target antigen to a whole antibody, and may be generated by modifying the whole antibody (e.g., by enzymatic or chemical cleavage) or by synthesizing de novo using recombinant DNA technology or peptide synthesis. Antigen-binding molecules may comprise, for example, other protein or artificial scaffolds having grafted CDRs or CDR derivatives. Such scaffolds include, but are not limited to, antibody-derived scaffolds containing mutations introduced to stabilize the three-dimensional structure of the antigen-binding molecule, and fully synthetic scaffolds comprising biocompatible polymers. See, for example, Korndorfer et al., 2003, Proteins: Structure, Function, and Bioinformatics, Volume 53, Issue 1:121-129 (2003); Roque et al., Biotechnol. Prog. 20:639-654 (2004). Additionally, peptide antibody mimetics ("PAMs") can be used, as well as antibody mimetic-based scaffolds that utilize fibronectin components as scaffolds.

[0056] Antigen-binding molecules can also include proteins containing one or more antibody fragments, either incorporated into a single polypeptide chain or into multiple polypeptide chains. For example, antigen-binding molecules include diabodies (see, e.g., European Patent No. 404,097; International Publication No. WO 93 / 11161; and Hollinger et al., Proc. Natl. Acad. Sci. USA, Vol. 90:6444-6448, 1993); intracellular antibodies; domain antibodies (containing a single VL domain or VH domain); Main, or two or more VH domains linked by a peptide linker; Ward et al. al., Nature, Vol. 341:544-546, 1989); maxibodies (two scFvs fused to an Fc region, see Fredericks et al., Protein Engineering, Design & Selection, Vol. 17:95-106, 2004 and Powers et al. al., Journal of Immunological Methods, Vol. 251:123-135, 2001); triabody; tetrabody; minibody (in which an scFv is fused to a CH3 domain; see Olafsen et al., Protein Eng Des Sel., Vol. 17:315-23, 2004); peptibodies (in which one or more peptides are attached to an Fc region; see WO 00 / 24782); linear antibodies (in which a tandem pair of Fd segments (VH-CH1-VH-CH1) are coupled with a complementary light chain polypeptide to form a pair of antigen-binding regions; see Zapata et al., Protein Eng., Vol. 8:1057-1062, 1995); small modular immunopharmaceuticals (see U.S. Patent Application Publication No. 20030133939); and immunoglobulin fusion proteins (e.g., IgG-scFv, IgG-Fab, 2scFv-IgG, 4scFv-IgG, VH-IgG, IgG-VH, and Fab-scFv-Fc).

[0057] In certain embodiments, the antigen-binding molecule may have the structure of, for example, an immunoglobulin. An "immunoglobulin" is a tetrameric molecule in which each tetramer contains two identical pairs of polypeptide chains, each pair having one "light" chain (approximately 25 kDa) and one "heavy" chain (approximately 50-70 kDa). The amino-terminal portion of each chain contains a variable region consisting of approximately 100-110 or more amino acids, which is primarily responsible for antigen recognition. The carboxy-terminal portion of each chain defines a constant region, which is primarily responsible for effector function.

[0058] Unless otherwise specified, the complementarity defining the regions disclosed herein is according to the IMGT definition. In some embodiments, any of the CDRs disclosed herein can be alternatively interpreted according to definitions accepted by those skilled in the art, such as the Kabat definition, the Chothia definition, etc.

[0059] The term "humanized" refers to hybrid immunoglobulins in which, when provided to a non-human (e.g., rodent or primate) antibody, the immunoglobulin chains or fragments thereof contain minimal sequences derived from the non-human immunoglobulin.

[0060] As used herein, the term "cytokine" refers to small proteins, polypeptides, or peptides involved in inflammatory signaling, or to proteins produced by one cell population that act on another cell as an intercellular mediator or that have an autocrine effect on the cell that produces them. Cytokines include chemokines, interferons, interleukins, lymphokines, monokines, tumor necrosis factors, CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL29, CCL30, CCL31, CCL32, CCL33, CCL34, CCL35, CCL36, CCL37, CCL38, CCL39, CCL40, CCL41, CCL42, CCL43, CCL44, CCL45, CCL46, CCL47, CCL48, CCL49, CCL50, CCL51, CCL52, CCL53, CCL54, CCL55, CCL56, CCL57, CCL58, CCL59, CCL60, CCL61, CCL62, CCL63, CCL64, CCL65, CCL66, CCL67, CCL68, CCL69, CCL70, CCL71, CCL72, CCL73, CCL74, CCL75, CCL76, CCL77, CCL78, CCL79, CCL80, CCL81, CCL82, CCL83, CCL84, CCL85, CCL CL27, CCL28, CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14 , CXCL15, CXCL16, CXCL17, CX3CL1, XCL1, XCL2, INFα, INFβ, INFγ, IL-1, IL-1a, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8 , IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-17A-F, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL -27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, IL-34, IL-35, IL-36, IL-37, IL-38, adesleukin, GM-CSF, TNFα, TNFβ, TNFγ, TGF-I-3 Examples of such proteins include, but are not limited to, TNFSF4, TNFSF5, TNFSF6, TNFSF7, TNFSF8, TNFSF9, TNFSF10, TNFSF11, TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18, or TNFSF19, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), CNTF-like cytokine (CLC), cardiotrophin (CT), Kit ligand (KL), or any combination thereof.

[0061] As used herein, the terms "treat" or "treatment" (as well understood in the art) refer to an approach to obtain beneficial or desired results in a subject's condition, including clinical results. Beneficial or desired clinical results include, but are not limited to, relief or amelioration of one or more symptoms or conditions, attenuation of the extent of the disease, stabilization of the condition (i.e., not worsening), prevention of disease transmission or spread, delay or slowing of disease progression, improvement or palliation of the condition, attenuation of disease recurrence, and remission, whether partial or complete and whether detectable or undetectable. "Treat" and "treatment," as used herein, also include prophylactic treatment. Treatment involves administering a therapeutically effective amount of an active agent to a subject. This administration step may consist of a single administration or a series of administrations. The composition is administered to the subject in an amount and for a duration sufficient to treat the subject. The length of the treatment period depends on various factors, such as the severity of the condition, the age and genetic profile of the subject, the concentration of the active agent, the activity of the composition used in the treatment, or a combination thereof. It will also be understood that the effective amount of an agent used for treatment or prevention may increase or decrease over the course of a particular treatment or prevention regime. Dosage variations may occur, but can be determined by standard diagnostic tests known in the art. In some cases, chronic administration may be necessary.

[0062] The term "effective amount" or "effective dose," as used herein, has its plain and ordinary meaning as understood in light of the present specification and refers to the amount of a described composition or compound that produces a specified observable effect. The actual dosage level of the active ingredient in the active composition of the inventive subject matter of the present disclosure can be varied so that an amount of the active composition or compound is administered that is effective to achieve a specified response for a particular subject and / or application. The selected dosage level can vary depending on various factors, including, but not limited to, the activity of the composition, dosage form, route of administration, combination with other drugs or treatments, the severity of the condition being treated, and the physical condition and medical history of the subject being treated. In some embodiments, a minimal amount is administered, and the dose is gradually increased to the lowest effective amount to avoid dose-limiting toxicity. Determination and adjustment of the effective amount, as well as evaluation of when and how to make such adjustments, are contemplated herein.

[0063] In some non-limiting embodiments, an effective amount or effective dose of a composition or compound relates to an amount or dose that provides a significant, measurable, or sufficient therapeutic effect toward the treatment of any one or more of the diseases provided herein, such as insulin resistance, diabetes mellitus, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer. In some embodiments, an effective amount or dose of a composition or compound may treat, ameliorate, or prevent the progression of any one or more symptoms of the diseases provided herein.

[0064] The term "administering" includes oral administration, topical contact, administration as a suppository, intravenous administration, intraperitoneal administration, intramuscular administration, intralesional administration, intrathecal administration, intranasal administration, or subcutaneous administration, or implantation of a sustained-release device (e.g., a mini-osmotic pump) to a subject. Administration is by any route, including parenteral and transmucosal routes (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, for example, intravenous, intramuscular, intraarteriolar, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial administration. Other delivery modes include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, and the like. "Co-administering" means that a first compound described herein is administered simultaneously with, immediately before, or immediately after the administration of a second compound described herein.

[0065] As used herein, the term "therapeutic target" refers to a gene or gene product whose activity, when modulated (e.g., by modulating expression, biological activity, etc.), can result in modulation of a disease phenotype. As used throughout, "modulation" is intended to refer to an increase or decrease in the indicated phenomenon (e.g., modulation of biological activity refers to an increase in biological activity or a decrease in biological activity).

[0066] As used herein, "pharmaceutically acceptable" has its plain and ordinary meaning as understood in light of the present specification and refers to a carrier, excipient, and / or stabilizer that is non-toxic or has an acceptable level of toxicity to cells or mammals exposed thereto at the dosages and concentrations employed. "Pharmaceutically acceptable," "diluent," "excipient," and / or "carrier," as used herein, has its plain and ordinary meaning as understood in light of the present specification and is intended to encompass any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonicity and absorption delaying agents, and the like, compatible with administration to a vertebrate host, such as a human, cat, or dog. Typically, pharmaceutically acceptable diluents, excipients, and / or carriers are those approved by a regulatory agency of a federal, state, or other regulatory body, or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia, for use in humans and animals, including non-human mammals such as cats and dogs. The terms diluent, excipient, and / or carrier may refer to a diluent, adjuvant, excipient, or vehicle with which a pharmaceutical formulation is administered. Such pharmaceutical diluents, excipients, and / or carriers may be sterile liquids such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin. Water, saline, and aqueous dextrose and glycerol solutions may be used as liquid diluents, excipients, and / or carriers, particularly for injectable formulations. Suitable pharmaceutical diluents and / or excipients include sugar, starch, glucose, fructose, lactose, sucrose, maltose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, salt, sodium chloride, nonfat dry milk, glycerol, propylene, glycol, water, ethanol, and the like. A non-limiting example of a physiologically acceptable carrier is a pH-buffered aqueous solution.Physiologically acceptable carriers may also include one or more of the following: antioxidants such as ascorbic acid, low molecular weight (less than about 10 residues) polypeptides, proteins such as serum albumin, gelatin, immunoglobulins, hydrophilic polymers such as polyvinylpyrrolidone, amino acids, carbohydrates such as glucose, mannose, or dextrin, chelating agents such as EDTA, sugar alcohols such as glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, isomalt, maltitol, or lactitol. , salt-forming counterions such as sodium, and nonionic surfactants such as TWEEN®, polyethylene glycol (PEG), and PLURONICS®. The formulations, if desired, may also contain minor amounts of wetting agents, bulking agents, emulsifying agents, or pH buffering agents. These formulations can take the form of solutions, suspensions, emulsions, sustained-release formulations, etc. The formulation should suit the mode of administration.

[0067] The term "pharmaceutically acceptable salt" has its plain and ordinary meaning as understood in light of this specification and includes relatively non-toxic, inorganic and organic, acid or base addition salts of compositions or excipients, including, but not limited to, analgesics, therapeutic agents, other substances, etc. Examples of pharmaceutically acceptable salts include those derived from mineral acids such as hydrochloric acid and sulfuric acid, and those derived from organic acids such as ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc. Examples of inorganic bases suitable for forming salts include hydroxides, carbonates, and bicarbonates of ammonia, sodium, lithium, potassium, calcium, magnesium, aluminum, zinc, and the like. Salts may also be formed with suitable organic bases, including those that are non-toxic and strong enough to form such salts. For example, classes of such organic bases may include, but are not limited to, mono-, di-, and trialkylamines, including methylamine, dimethylamine, and triethylamine; mono-, di-, or trihydroxyalkylamines, including monoethanolamine, diethanolamine, and triethanolamine; amino acids, including glycine, arginine, and lysine; guanidine; N-methylglucosamine; N-methylglucamine; L-glutamine; N-methylpiperazine; morpholine; ethylenediamine; N-benzylphenethylamine; trihydroxymethylaminoethane.

[0068] As used herein, "carrier" refers to a compound, particle, solid, semi-solid, liquid, or diluent that facilitates the passage, delivery, and / or uptake of a compound into cells, tissues, and / or organs. For example, but not limited to, lipid nanoparticles (LNPs) are a type of carrier that can encapsulate oligonucleotides to protect them from degradation during passage through the bloodstream and / or facilitate delivery to a desired organ, such as the lungs.

[0069] As used herein, "diluent" refers to an ingredient in a pharmaceutical composition that has no pharmacological activity but may be pharmaceutically necessary or desirable. For example, a diluent may be used to increase the bulk of a potent drug whose mass is too small for manufacture and / or administration. A diluent may also be a liquid for dissolving a drug to be administered by injection, ingestion, or inhalation. A common form of diluent in the art is a buffered aqueous solution, such as, but not limited to, phosphate buffered saline, which mimics the composition of human blood.

[0070] The term "excipient" has its ordinary meaning as understood in light of this specification and refers to an inert substance, compound, or material added to a pharmaceutical composition to provide, but not limited to, bulk, consistency, stability, binding ability, lubricity, disintegration ability, etc. to the composition. Excipients with desirable properties include preservatives, adjuvants, stabilizers, solvents, buffers, diluents, solubilizers, detergents, surfactants, chelating agents, antioxidants, alcohols, ketones, aldehydes, ethylenediaminetetraacetic acid (EDTA), citric acid, salt, sodium chloride, sodium bicarbonate, sodium phosphate, sodium borate, sodium citrate, potassium chloride, potassium phosphate, magnesium sulfate, sugars, glucose, dextran, fructose, mannose, lactose, galactose, sucrose, sorbitol, cellulose, methylcellulose, hydroxypropylmethylcellulose (hypromellose), glycerin, polyvinyl alcohol, povidone, propylene glycol, serum, amino acids, polyethylene glycol, polysorbate 20, polysorbate 80, deoxycholate, Examples of suitable anti-inflammatory agents include, but are not limited to, sodium hydroxybenzoate, sodium taurodeoxycholate, magnesium stearate, octylphenol ethoxylate, benzethonium chloride, thimerosal, gelatin, esters, ethers, 2-phenoxyethanol, urea, or vitamins, or any combination thereof. The amount of excipient may be present in the pharmaceutical composition in a percentage that is 0 w / w%, 0.1 w / w%, 0.2 w / w%, 0.3 w / w%, 0.4 w / w%, 0.5 w / w%, 0.6 w / w%, 0.7 w / w%, 0.8 w / w%, 0.9 w / w%, 1 w / w%, 2 w / w%, 3 w / w%, 4 w / w%, 5 w / w%, 6 w / w%, 7 w / w%, 8 w / w%, 9 w / w%, 10 w / w%, 20 w / w%, 30 w / w%, 40 w / w%, 50 w / w%, 60 w / w%, 70 w / w%, 80 w / w%, 90 w / w%, 95 w / w%, 100 w / w%, or any weight percentage within a range defined by any two of the above numbers.

[0071] Additional excipients with desirable properties include preservatives, adjuvants, stabilizers, solvents, buffers, diluents, solubilizers, detergents, surfactants, chelating agents, antioxidants, alcohols, ketones, aldehydes, ethylenediaminetetraacetic acid (EDTA), tris(hydroxymethyl)aminomethane (Tris), citric acid, ascorbic acid, acetic acid, salts, phosphates, citrates, acetates, succinates, chlorides, bicarbonates, borates, sulfates, sodium chloride, sodium bicarbonate, sodium phosphate, sodium borate, sodium citrate, potassium chloride, potassium phosphate, magnesium sulfate, sugars, glucose, dextran 40, fructose, mannose, lactose, trehalose, galactose, sucrose, sorbitol, mannitol, cellulose, The preferred stimulants include, but are not limited to, glucose, serum, amino acids, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer, poloxamer 188, sodium deoxycholate, sodium taurodeoxycholate, magnesium stearate, octylphenol ethoxylate, benzethonium chloride, thimerosal, gelatin, esters, ethers, 2-phenoxyethanol, urea, or vitamins, or any combination thereof. Some excipients may be in residual amounts or contaminants from the manufacturing process, including, but not limited to, serum, albumin, ovalbumin, antibiotics, inactivating agents, formaldehyde, glutaraldehyde, β-propiolactone, gelatin, cell debris, nucleic acids, peptides, amino acids, or growth media components, or any combination thereof.The amount of excipient may be present in the formulation in a percentage that is at least 0 w / w%, 0.1 w / w%, 0.2 w / w%, 0.3 w / w%, 0.4 w / w%, 0.5 w / w%, 0.6 w / w%, 0.7 w / w%, 0.8 w / w%, 0.9 w / w%, 1 w / w%, 2 w / w%, 3 w / w%, 4 w / w%, 5 w / w%, 6 w / w%, 7 w / w%, 8 w / w%, 9 w / w%, 10 w / w%, 20 w / w%, 30 w / w%, 40 w / w%, 50 w / w%, 60 w / w%, 70 w / w%, 80 w / w%, 90 w / w%, 95 w / w%, 100 w / w%, or any weight percentage within a range defined by any two of the above numbers.

[0072] As used herein, the term "purity" of any given substance, compound, or material refers to the amount of that substance, compound, or material actually present compared to the amount expected to be present. For example, a substance, compound, or material may be at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% pure, including all decimal points in between. Purity may be affected by unwanted impurities, including, but not limited to, by-products, isomers, enantiomers, degradation products, solvents, carriers, vehicles, or contaminants, or any combination thereof. Purity may be measured by any method, including chromatography, liquid chromatography, gas chromatography, spectroscopy, ultraviolet-visible spectroscopy, infrared spectroscopy, mass spectrometry, nuclear magnetic resonance spectroscopy, gravimetry, or titration, or by any other method. The present invention can be measured by techniques including, but not limited to, fluoroscopy, fluorometric analysis, or any combination thereof.

[0073] As used herein, the terms "standard of care," "best practice," and "standard of care" refer to a treatment that is recognized by physicians as appropriate, correct, effective, and / or widely used for a particular disease. The standard of care for a particular disease depends on many factors, including the biological effectiveness of the treatment, the area or location in the body, the patient's condition (e.g., age, weight, sex, genetic risk, other physical disorders, secondary conditions), toxicity, metabolism, bioaccumulation, therapeutic index, dosage, and other factors known in the art. Determining the standard of care for a disease also depends on establishing safety and efficacy in clinical trials standardized by regulatory agencies such as the U.S. Food and Drug Administration, the International Conference on Harmonization, Health Canada, the European Medicines Agency, the Agency for Therapeutic Goods and Medicines, the Central Therapeutic Goods Control Organization, the National Medical Products Administration, the Pharmaceuticals and Medical Devices Agency, the Ministry of Food and Drug Safety, and the World Health Organization. Standard treatments for a disease may include, but are not limited to, surgery, radiation therapy, chemotherapy, targeted therapy, or immunotherapy.

[0074] As used herein, the term "insulin resistance" is understood in the art and refers to the phenomenon in which a subject's cells become less sensitive to insulin, whether produced endogenously by the subject's pancreas or administered exogenously for therapeutic purposes. Insulin is necessary to signal cells to take up glucose for use as an energy source. Excessive blood glucose and / or elevated blood insulin levels (which may also be elevated by the pancreas in response to high blood glucose levels) can cause cells to become less responsive to normal levels of insulin release. This can lead to prediabetes and type 2 diabetes, among other conditions, but insulin resistance has also been associated with other diseases and disorders, such as metabolic syndrome, obesity, muscle wasting, hyperinsulinemia, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovarian syndrome, pancreatic cancer-related diabetes mellitus (PCDM), and cancer. Furthermore, while insulin resistance is not typically the primary cause of type 1 diabetes, type 1 diabetes can also develop insulin resistance.

[0075] Also provided herein are methods for "improving insulin sensitivity" in cells, patients, etc., where "improving insulin sensitivity" refers to improving insulin resistance and increasing the relative response of cells or patients to normal insulin levels. Insulin sensitivity is the ability of insulin to remove excess glucose from the bloodstream by inducing glucose uptake by peripheral tissues, such as skeletal muscle and adipose tissue. Diabetes is a metabolic disorder caused by impaired insulin secretion and insulin action (otherwise known as insulin sensitivity in insulin-responsive tissues, which results in glucose clearance). Improvements in insulin sensitivity can be measured through approaches commonly known in the art, such as measuring a patient's blood glucose or blood insulin levels, a glucose tolerance test, or a hyperinsulinemic-euglycemic clamp. In in vitro studies, improvements in insulin sensitivity can be measured indirectly according to the glucose transporter 1 (GLUT1) or glucose transporter 4 (GLUT4) translocation insulin stimulation index. Information regarding this measurement can be found, for example, in: Sun Y, Chiu TT, Foley KP, Bilan PJ, Klip A. (2014) “Myosin Va mediates Rab8A-regulated GLUT4 vesicle exocytosis in insulin-stimulated muscle cells”. Mol Biol Cell. 25: 1159-70, and Tunduguru R, Zhang J, Aslamy A, Salunkhe VA, Brozinick JT, Elmendorf JS, Thurmond DC. “The actin-related p41ARC subunit contributes to p21-activated ki These methods are known to those skilled in the art, as set forth in "Patient with a Glucose-1 Protein (PAK1)-Mediated Glucose Uptake into Skeletal Muscle Cells." J Biol Chem. 2017 Sep 25. pii: jbc.M117.801340, each of which is expressly incorporated herein by reference in its entirety. For example, improvements in insulin sensitivity with an anti-Gal3 antibody or binding fragment thereof can be compared to other therapeutic regimens, such as dietary modifications, weight loss, exercise, metformin, and thiazolidinediones, that are indicated for insulin-resistant patients.

[0076] As used herein, the term "glucose transporter 1 (GLUT1)" refers to the major insulin-independent glucose transporter that is highly conserved among mammals and widely found in various tissues. Dysfunction in GLUT1 has been associated with GLUT1 deficiency syndrome (de vivo disease), idiopathic generalized epilepsy, dystonia, and stomatin-deficient cryohydrocytosis. An exemplary sequence of human GLUT1 is provided as SEQ ID NO: 1618. GLUT1 is also known as SLC2A1.

[0077] As used herein, the term "glucose transporter 4 (GLUT4)" refers to an insulin-responsive glucose transporter expressed by cells. An exemplary sequence of human GLUT4 is provided as SEQ ID NO: 950. GLUT4 is a transmembrane protein that facilitates the exchange of glucose between cells and the bloodstream. GLUT4 stored in intracellular vesicles translocates to the plasma membrane after an insulin-induced signaling cascade. In insulin-resistant cells, this translocation process is inhibited, resulting in less GLUT4 being delivered to the plasma membrane and abnormal glucose uptake. GLUT4 is also known as SLC2A4.

[0078] Also provided herein are methods directed to "enhancing GLUT translocation." This term refers to the improved transport and activity of GLUTs in cells, such as insulin-resistant cells, which may originally exhibit reduced GLUT translocation compared to normal cells. In some embodiments, the GLUT is GLUT1 and / or GLUT4. Enhancement of GLUT translocation can also be applied to the restoration of dysfunctional GLUT translocation caused by adverse cellular function. In some embodiments, as shown herein, GLUT translocation is inhibited by Gal3. Application of a Gal3 inhibitor, such as an anti-Gal3 antibody, can improve GLUT translocation and thereby restore Gal3 activity. In some embodiments, the enhancement can be at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%, or any percentage enhancement within a range defined by any two of the above values.

[0079] As used herein, the term "inhibit" refers to a suppression or reduction in an expected activity, such as a cellular activity. The suppression or reduction can be at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%, or any percentage within a range defined by any two of the above values, where 100% suppression or reduction represents complete inhibition and any lower percentage represents partial inhibition. The suppression or reduction of the expected activity can be observed by direct or indirect methods. For example, as disclosed herein, Gal3 has been shown to inhibit GLUT (e.g., GLUT1 and / or GLUT4) translocation in cells. This inhibition of GLUT translocation (as well as the inhibition of the aforementioned by, for example, one or more of the proteins disclosed herein) can be observed by direct or indirect methods. Potential reversal of inhibition) can be observed through direct observation of intracellular GLUT translocation or abundance, or through observation of indirect properties such as glucose uptake.

[0080] The term "half maximal inhibitory concentration," often abbreviated as "IC50," refers to the concentration of a substance (e.g., a compound or an antibody) that results in 50% inhibition of a biological process or a component of that process (e.g., protein binding).

[0081] The term "w / w%" or "wt / wt%" refers to the percentage expressed as the weight of an ingredient or agent relative to the total weight of the composition, multiplied by 100.

[0082] It is understood that antibodies having the antibody names described herein may be referred to using shortened versions of the antibody names, as long as they do not conflict with other antibodies described herein. For example, F846C.1B2 may also be referred to as 846C.1B2, or 846.1B2. This may also refer to fragments of the antibody (e.g., having the same one, three, or six CDRs).

[0083] Exemplary Anti-Gal3 Antibodies and Binding Fragments Thereof Disclosed herein and applicable to any of the methods or uses disclosed herein are anti-Gal3 antibodies or binding fragments thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the N-terminal domain of Gal3, the N-terminus of Gal3, or the tandem repeat domain (TRD) of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the N-terminus of Gal3, the N-terminal domain of Gal3, or the TRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the C-terminus of Gal3, the C-terminal domain of Gal3, or the CRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the C-terminus of Gal3, the C-terminal domain of Gal3, or the CRD of Gal3. In some embodiments, any of the anti-Gal3 antibodies or binding fragments thereof, or any of the anti-Gal3 antibodies or binding fragments provided herein, may be replaced with an antigen-binding molecule that binds to Gal3.

[0084] In some embodiments, the constructs provided herein are provided in a subcutaneous or intravenous dosage form. In some embodiments, the constructs provided herein are provided in a subcutaneous dosage form.

[0085] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising V L -CDR1, V L -CDR2, and V L - a light chain variable region comprising CDR3. In some embodiments, the V H-CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of any of SEQ ID NOs: 27-70. H -CDR2 is at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 11 In some embodiments, the V comprises an amino acid sequence having 5%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity. H -CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of any of SEQ ID NOs: 112-169, 802, 953, and 954. In some embodiments, the V L-CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 170 to 220. In some embodiments, the V L -CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of any of SEQ ID NOs: 221-247. L - CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence of any of SEQ ID NOs: 248-296. In some embodiments, the antibody comprises a VL sequence, a VH sequence, a VL / VH pairing, and / or a VL / VH pairing selected from the heavy and light chain sequences shown in Figure 25. H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, V L-comprises one or more sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to CDR3 (including 1, 2, 3, 4, or 5 amino acid substitutions in any one or more of these CDRs).

[0086] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising V L -CDR1, V L -CDR2, and V L - a light chain variable region comprising CDR3. In some embodiments, the V H -CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to the amino acid sequence of any of SEQ ID NOs: 27-70. H -CDR2 has at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, In some embodiments, the V comprises an amino acid sequence having 5%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity. H -CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to the amino acid sequence of any of SEQ ID NOs: 112-169, 802, 953, and 954. In some embodiments, the V L -CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to the amino acid sequence of any of SEQ ID NOs: 170-220. L -CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to the amino acid sequence of any of SEQ ID NOs: 221-247. L- CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to the amino acid sequence of any of SEQ ID NOs: 248-296. In some embodiments, the antibody comprises a VL sequence, a VH sequence, a VL / VH pairing, and / or a VL / VH pairing selected from the heavy and light chain sequences shown in Figure 25. H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, V L -Comprises one or more sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to CDR3 (including 1, 2, 3, 4, or 5 amino acid substitutions in any one or more of these CDRs).

[0087] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising V L -CDR1, V L -CDR2, and V L - a light chain variable region comprising CDR3. In some embodiments, the V H-CDR1 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions with respect to the amino acid sequence of any one of SEQ ID NOs: 27 to 70. In some embodiments, H -CDR2 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to the amino acid sequence of any of SEQ ID NOs: 71 to 111, 801, 951, and 952. In some embodiments, the V H -CDR3 has at least 0, 1, 2, 3, 4, 5, or 6 amino acids with respect to any of the amino acid sequences of SEQ ID NOs: 112 to 169, 802, 953, and 954. In some embodiments, the V L -CDR1 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions with respect to the amino acid sequence of any one of SEQ ID NOs: 170 to 220. In some embodiments, L -CDR2 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to the amino acid sequence of any of SEQ ID NOs: 221 to 247. L - CDR3 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to the amino acid sequence of any one of SEQ ID NOs: 248 to 296.

[0088] In some embodiments, the antibody or binding fragment thereof is a V L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, and V H -Contains CDR3 combinations.

[0089] In some embodiments, the antibody or binding fragment thereof comprises V H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L-CDR2, and V L -CDR3 combinations, one or more of which CDRs are defined by a consensus sequence. The consensus sequences provided herein were obtained from the alignment of the CDRs shown in Figures 37A-37B. However, alternative alignments may be performed (e.g., using global or local alignments, or using techniques such as hidden Markov models, seeded guide trees, etc.). It is also envisioned that alternative consensus sequences may be obtained in this manner, using various algorithms such as the guide tree, the Needleman-Wunsch algorithm, or the Smith-Waterman algorithm.

[0090] In some embodiments, the V H CDR1 has the formula X1X2X3X4X5X6X7X8X9X 10 X is defined as: X1 is E, G, or R; X2 is F, N, or Y; X3 is A, I, K, N, S, or T; X4 is F, I, or L; X5 is I, K, N, R, S, or T; X6 is D, G, I, N, S, or T; X7 is F, G, H, S, or Y; X8 is no amino acid, A, D, G, I, M, N, T, V, W, or Y; X9 is no amino acid, M, or Y; X 10 is no amino acid or G; in some embodiments, the V H - CDR1 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. H - CDR1 comprises a sequence with 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0091] In some embodiments, the V H CDR2 has the formula X1X2X3X4X5X6X7X8X9X10 X is A, D, F, H, K, L, N, S, W, or Y; X is A, D, P, S, T, W, or Y; X is D, E, G, H, K, N, S, V, or Y; X is D, G, I, K, N, Q, R, S, V, or Y; X is A, D, E, G, I, K, N, P, S, T, V, or Y; 10 is no amino acid, I, P, S, or T. In some embodiments, the V H - CDR2 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. H - CDR2 comprises a sequence with 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0092] In some embodiments, the V H CDR3 has the formula X1X2X3X4X5X6X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 X 17 X 18 X 19 X 20 X 21 X 22 X 23 X 24 X 25X1 is no amino acid, or A; X2 is no amino acid, A, R, or Y; X3 is no amino acid, A, F, H, K, L, R, S, or V; X4 is no amino acid, A, D, K, N, R, S, or T; X5 is no amino acid, A, D, G, H, I, L, N, P, R, S, T, V, or Y; X6 is no amino acid, A, D, G, H, K, N, P, Q, R, S, or Y; X7 is no amino acid, D, F, G, H, P, R, S, W, or Y; X8 is no amino acid, A, D, E, G, I, R, or S; X9 is no amino acid, A, C, D, E, F, G, I, N, R, S, T, V, or Y; X 10 is no amino acid, A, D, M, P, R, S, T, V, or Y; X 11 is no amino acid, A, D, E, F, L, T, V, or Y; X 12 is no amino acid, A, G, L, M, R, or T; X 13 is no amino acid, A, D, E, F, G, R, S, T, or V; X 14 is no amino acid, A, D, G, L, P, Q, R, S, T, V, or Y; X 15 is no amino acid, A, D, G, N, S, V, W, or Y; X 16 is no amino acid, A, D, E, F, L, P, T, V, W, or Y; X 17 is no amino acid, F, I, L, M, R, or Y; X 18 is no amino acid, A, D, G, N, or T; X 19 is no amino acid, F, N, S, T, V, or Y; X 20 is no amino acid or L; X 21 is no amino acid or A; X 22 is no amino acid or W; X 23 is no amino acid or F; X 24 is no amino acid or A; X 25 is no amino acid or Y. In some embodiments, the V H- CDR3 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. H - CDR3 comprises a sequence with 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0093] In some embodiments, the V L CDR1 has the formula X1X2X3X4X5X6X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 X 17 X1 is no amino acid, or R; X2 is no amino acid, or S; X3 is no amino acid, S, or T; X4 is no amino acid, E, G, K, Q, or R; X5 is no amino acid, A, D, G, I, N, or S; X6 is no amino acid, I, L, or V; X7 is no amino acid, F, L, S, or V; X8 is no amino acid, D, E, H, N, S, T, or Y; X9 is no amino acid, D, E, I, K, N, R, S, T, or V; X 10 is no amino acid, D, H, N, R, S, or Y; X 11 is no amino acid, A, G, N, S, T, or V; X 12 is no amino acid, A, I, K, N, Q, T, V, or Y; X 13 is no amino acid, D, G, H, K, N, S, T, or Y; X 14 is no amino acid, C, F, I, N, S, T, V, or Y; X 15 is no amino acid, D, L, N, W, or Y; X 16 is no amino acid, N, or D; X 17 is no amino acid or D. In some embodiments, the V L- CDR1 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. L - CDR1 comprises a sequence with 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0094] In some embodiments, the V L - CDR2 is defined by the formula X1X2X3X4X5X6X7X8, where X1 is no amino acid, K, L, N, Q, or R; X2 X is no amino acid, A, L, M, or V; X3 is no amino acid, C, K, or S; X4 is no amino acid or T; X5 is no amino acid, A, E, F, G, H, K, Q, R, S, W, or Y; X6 is no amino acid, A, G, or T; X7 is no amino acid, I, K, N, S, or T; and X8 is no amino acid, N, or S. In some embodiments, the V L - CDR2 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. L - CDR2 comprises a sequence with 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0095] In some embodiments, the V L CDR3 has the formula X1X2X3X4X5X6X7X8X9X 10X is no amino acid, A, E, F, H, L, M, Q, S, V, or W; X is A, H, or Q; X is D, F, G, H, L, M, N, Q, S, T, W, or Y; X is no amino acid or W; X is A, D, I, K, L, N, Q, R, S, T, V, or Y; X is D, E, H, I, K, L, N, Q, S, or T; X is D, F, K, L, N, P, S, T, V, W, or Y; X is H, P, or S; X is F, L, P, Q, R, T, W, or Y; 10 is no amino acid, T, or V. In some embodiments, the V L - CDR3 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. L - CDR3 comprises a sequence with 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0096] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 940, 955-968, 1067-1109, and 1415-1439. In some embodiments, the light chain variable region of the antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, and 1440-1464. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof.

[0097] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to a sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 940, 955-968, 1067-1109, and 1415-1439. In some embodiments, the light chain variable region of the antibody or binding fragment thereof has a sequence identity with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, or 97% of a sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, and 1440-1464. , 97%, 98%, 99%, or 100% similarity. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof.

[0098] In some embodiments, the antibody comprises a VL sequence, a VH sequence, a VL / VH pairing, and / or a VL sequence set from the heavy and light chain sequences shown in FIG. 25. L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, V H -comprises one or more sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to CDR3 (including 1, 2, 3, 4, or 5 amino acid substitutions in any one or more of these CDRs).

[0099] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising V L -CDR1, V L -CDR2, and V L - a light chain variable region comprising CDR3. In some embodiments, the V H - CDR1 comprises one of the amino acid sequences of SEQ ID NOs: 27 to 70, H - CDR2 comprises one of the amino acid sequences of SEQ ID NOs: 71 to 111, 801, 951, 952, H-CDR3 comprises one of the amino acid sequences of SEQ ID NOs: 112 to 169, 802, 953, 954, L - CDR1 comprises one of the amino acid sequences of SEQ ID NOs: 170 to 220, L - CDR2 comprises one of the amino acid sequences of SEQ ID NOs: 211 to 247, L - CDR3 comprises one of the amino acid sequences of SEQ ID NOs: 248 to 296, and the heavy chain variable region has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 10% identity with one of the amino acid sequences of SEQ ID NOs: 297 to 373, 803, 806 to 820, 940, 955 to 968, 1067 to 1109, and 1415 to 1439. 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one of the amino acid sequences of SEQ ID NOs: 374 to 447, 821 to 835, 941 to 943, 969 to 982, 1110 to 1152, and 1440 to 1464.

[0100] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, and 1490-1514. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof.

[0101] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to a sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% similarity to a sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, and 1490-1514. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof.

[0102] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region and a light chain variable region. In some embodiments, the heavy chain variable region is paired with an IgG4 heavy chain constant domain, an IgG2 heavy chain constant domain, or an IgG1 heavy chain constant domain. In some embodiments, the IgG4 heavy chain constant domain, the IgG2 heavy chain constant domain, or the IgG1 heavy chain constant domain is human or mouse. In some embodiments, the IgG4 heavy chain constant domain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 945. In some embodiments, the IgG4 heavy chain constant domain is an S228P mutant. In some embodiments, the IgG2 heavy chain constant domain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 947 or SEQ ID NO: 948. In some embodiments, the IgG2 heavy chain constant domain is a LALAPG mutant or a LALA mutant. In some embodiments, the IgG1 heavy chain constant domain is a KEM mutant, a REM mutant, or a LALAPGv2 mutant. In some embodiments, the IgG1 heavy chain constant domain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 1615, 1616, or 1617. In some embodiments, the light chain variable region is paired with an IgG4 kappa chain constant domain.In some embodiments, the IgG4 κ chain constant domain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 946. In some embodiments, the light chain variable region and / or heavy chain variable region may be selected from those shown in Figures 21 and 22 and / or a combination of light chain variable regions and heavy chain variable regions as shown in Figure 24. In some embodiments, the light chain variable region and / or heavy chain variable region comprises one or more CDRs shown in Figures 19A-19C, one or more CDRs shown in Figures 20A-20C, and / or a combination of CDRs shown in Figure 23.

[0103] In some embodiments, the antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2 D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2 D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D 6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D 12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846T C.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11 B1, F847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846. 2B11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T .2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847 .15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1 , 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849 .4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 8 47.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847.4D3, 2D10-VH0-VL0, 2D 10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or a binding fragment thereof.

[0104] In some embodiments, the antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2 A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1 H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F84 7C.4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846T.1H2, 847.1 4H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 8 46T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15 H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849 .1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8 D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 8 47.13E2-mH0mL2, 847.12C4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 20H5.A3-VH3VL1,20H5.A3-VH3VL3、20H5.A3-VH4VL1、20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、20H5.A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D1 0-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v2-QDT、2D10-hVH1-hVL1、2D10-hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-hVL4、 2D10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL4、20H5.A3-hIgG4(S228P)、20H5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0 mL1、798-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1mL1、798-9.20H5.A3-mH2mL0、798-9.20H5.A3-mH2mL1、20H5.A3-VH1VL1、20H5.A3-VH1VL2、20H5. A3-VH1VL3、20H5.A3-VH1VL4、20H5.A3-VH1VL5、20H5.A3-VH1VL6、20H5.A3-VH2VL3、20H5.A3-VH2VL4、20H5.A3-VH2VL5、20H5.A3-VH2VL6、20H5.A3- VH3VL5、20H5.A3-VH3VL6、20H5.A3-VH4VL3、20H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3-VH5VL5、20H5.A3-VH5VL6、20H5.A3-VH6 VL4、20H5.A3-VH6VL5、20H5.A3-VH6VL6、20H5.A3-VH7VL1、20H5.A3-VH7VL2、20H5.A3-VH7VL3、20H5.A3-VH7VL4、20H5.A3-VH7VL5、20H5.A3-VH7VL6 、20H5.A3_hVH3VL1-hIgG1(KEMv2)、20H5.A3_hVH3VL1-hIgG1(LALAPGv2)、20H5.A3_hVH3VL1-hIgG1(REM)、20H5.A3_hVH5VL1-hIgG1(KEMv2)、20H5.A3_hVH5VL1-hIgG1(LALAPGv2), 20H5.A3_hVH5VL1-hIgG1(REM), 20H5.A3_hVH6VL1-hIgG1(KEMv2), 20H5.A3_hVH6VL1-hIgG1 (LALAPGv2), 20H5.A3_hVH6VL1-hIgG1(REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2 L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0105] In some embodiments, the antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B 12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F 846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.1 1B1, F847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B 11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9、846T.4E11、846T.4F5、846T.8D1、847.10C9、847.11D6、847.15 D12、847.15F9、847.15H11、847.20H7、847.21B11、847.27B9、847.28D1、84 7.2B8、847.3B3、849.1D2、849.2D7、849.2F12、849.4B2、849.4F12、849.4F 2、849.5C2、849.8D12、F847C.21H6、849.5H1、847.23F11、847.16D10、847. 13E2-mH0mL1、847.13E2-mH0mL2、847.12C4、847.4D3、2D10-VH0-VL0、2D10 -hVH4-HVL1、2D10-hVH4-HVL2、2D10-hVH4-HVL3、2D10-hVH4-HVL4、2D10-h VH3-HVL1、2D10-hVH3-HVL2、2D10-hVH3-HVL3、2D10-hVH3-HVL4、20H5.A3-VH3VL1、20H5.A3-VH3VL3、20H5.A3-VH4VL1、20H5.A3-VH5VL1、20H5.A3-VH 5VL3、20H5.A3-VH6VL1、20H5.A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v 2-QDT、2D10-hVH1-hVL1、2D10-hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-h VL4、2D10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL 4、20H5.A3-hIgG4(S228P)、20H5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0mL1、798-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1mL1、798-9.20H5.A3 -mH2mL0、798-9.20H5.A3-mH2mL1、20H5.A3-VH1VL1、20H5.A3-VH1VL2、20H5.A3-VH1VL3、20H5.A3-VH1VL4、20H5.A3-VH1VL5、20H5.A3-VH1VL6、20H5.A3-VH2VL3, 20H5.A3-VH2VL4, 20H5.A3-VH2VL5, 20H5.A3-VH2VL6, 20H5. A3-VH3VL5, 20H5.A3-VH3VL6, 20H5.A3-VH4VL3, 20H5.A3-VH4VL4, 20H5.A 3-VH4VL5, 20H5.A3-VH4VL6, 20H5.A3-VH5VL5, 20H5.A3-VH5VL6, 20H5.A3 -VH6VL4, 20H5.A3-VH6VL5, 20H5.A3-VH6VL6, 20H5.A3-VH7VL1, 20H5.A3- VH7VL2, 20H5.A3-VH7VL3, 20H5.A3-VH7VL4, 20H5.A3-VH7VL5, 20H5.A3-VH7VL6, 20H5.A3_hVH3VL1-hIgG1(KEMv2), 20H5.A3_hVH3VL1-hIgG1(LALA PGv2), 20H5.A3_hVH3VL1-hIgG1(REM), 20H5.A3_hVH5VL1-hIgG1(KEMv2), 20H5.A3_hVH5VL1-hIgG1(LALAPGv2), 20H5.A3_hVH5VL1-hIgG1(REM), 2 0H5.A3_hVH6VL1-hIgG1(KEMv2), 20H5.A3_hVH6VL1-hIgG1(LALAPGv2), 20H5.A3_hVH6VL1-hIgG1(REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6- H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H 3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4 L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof (e.g., CDR, VL, VH, LC, HC).

[0106] In some embodiments, the antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2 E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1 H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F 847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849C.8 D10, F849C.8H3, 846.2B11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846.2F 11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847 .10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11 , 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 84 9.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847 .23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847. 4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D 10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2 D10-VH0-v2-QDT、2D10-hVH1-hVL1、2D10-hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-hVL4、2D10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2 D10-hVH2-hVL4、20H5.A3-hIgG4(S228P)、20H5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0mL1、798-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1m L1、798-9.20H5.A3-mH2mL0、798-9.20H5.A3-mH2mL1、20H5.A3-VH1VL1、20H5.A3-VH1VL2、20H5.A3-VH1VL3、20H5.A3-VH1VL4、20H5.A3-VH1VL5、2 0H5.A3-VH1VL6、20H5.A3-VH2VL3、20H5.A3-VH2VL4、20H5.A3-VH2VL5、20H5.A3-VH2VL6、20H5.A3-VH3VL5、20H5.A3-VH3VL6、20H5.A3-VH4VL3、2 0H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3-VH5VL5、20H5.A3-VH5VL6、20H5.A3-VH6VL4、20H5.A3-VH6VL5、20H5.A3-VH6VL6、20 H5.A3-VH7VL1、20H5.A3-VH7VL2、20H5.A3-VH7VL3、20H5.A3-VH7VL4、20H5.A3-VH7VL5、20H5.A3-VH7VL6、20H5.A3_hVH3VL1-hIgG1(KEMv2)、20H5 .A3_hVH3VL1-hIgG1(LALAPGv2)、20H5.A3_hVH3VL1-hIgG1(REM)、20H5.A3_hVH5VL1-hIgG1(KEMv2)、20H5.A3_hVH5VL1-hIgG1(LALAPGv2)、20H5. A3_hVH5VL1-hIgG1(REM), 20H5.A3_hVH6VL1-hIgG1(KEMv2), 20H5.A3_hVH6VL1-hIgG1(LALAPGv2), 20H5.A3_hVH6VL1-hIgG1(REM), 21H6-H0L0, 21H6-H1L1, 2 1H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2 L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H and / or a binding fragment thereof.

[0107] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising V L -CDR1, V L -CDR2, and V L - a light chain variable region comprising CDR3. In some embodiments, the V H- CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 32. H - CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NOs: 801, 951, 952. H - CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NOs: 802, 953, 954. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 171. L- CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 222. In the embodiment, the above V L - CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 257.

[0108] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising V L -CDR1, V L -CDR2, and V L - a light chain variable region comprising CDR3. In some embodiments, the V H- CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 32. H - CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NOs: 801, 951, 952. H - CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NOs: 802, 953, 954. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 171. L- CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 222. L - CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 257.

[0109] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising V L -CDR1, V L -CDR2, and V L In some embodiments, the V H - CDR1 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 32. H- CDR2 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NOs: 801, 951, 952. In some embodiments, the V H - CDR3 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NOs: 802, 953, 954. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 171. In some embodiments, the V L - CDR2 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 222. L - CDR3 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 257.

[0110] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 806-813, 955-968. In some embodiments, the light chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 821-828, 969-982.

[0111] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences set forth in SEQ ID NOs: 806-813, 955-968. In some embodiments, the light chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences set forth in SEQ ID NOs: 821-828, 969-982.

[0112] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 836-843, 983-996. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences of SEQ ID NOs: 851-858, 997-1010.

[0113] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences set forth in SEQ ID NOs: 836-843, 983-996. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences of SEQ ID NOs: 851-858, 997-1010.

[0114] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising V L -CDR1, V L -CDR2, and V L In some embodiments, the V H - CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 37. H- CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 77. In some embodiments, the V H - CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 118. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 178. In some embodiments, the V L - CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 229. L- CDR3 is at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 11 %, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence.

[0115] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising V L -CDR1, V L -CDR2, and V L In some embodiments, the V H - CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 37. H- CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 77. In some embodiments, the V H - CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 118. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 178. In some embodiments, the V L - CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 229. In some embodiments, the V L- CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 256.

[0116] In some embodiments, an antibody or binding fragment thereof is provided. In some embodiments, the antibody or binding fragment thereof is an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is V H -CDR1, V H -CDR2, and V H -heavy containing CDR3 In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V chain variable region. L -CDR1, V L -CDR2, and V L In some embodiments, the V H - CDR1 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 37. H - CDR2 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 77. H - CDR3 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 118. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 178. In some embodiments, the V L- CDR2 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 229. L - CDR3 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to SEQ ID NO: 256.

[0117] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 814-820, 1067-1109. In some embodiments, the light chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 829-835, 1110-1152.

[0118] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences set forth in SEQ ID NOs: 814-820, 1067-1109. In some embodiments, the light chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences set forth in SEQ ID NOs: 829-835, 1110-1152.

[0119] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 844-850, 1153-1195. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 859-865, 1196-1238.

[0120] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, and the heavy chain is selected from the group consisting of any of the sequences set forth in SEQ ID NOs: 844-850, 1153-1195. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences of SEQ ID NOs: 859-865, 1196-1238.

[0121] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 1415-1439. In some embodiments, the light chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 1440-1464.

[0122] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences set forth in SEQ ID NOs: 1415-1439. In some embodiments, the light chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences set forth in SEQ ID NOs: 1440-1464.

[0123] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the sequences set forth in SEQ ID NOs: 1490-1514.

[0124] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences set forth in SEQ ID NOs: 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one of the sequences set forth in SEQ ID NOs: 1490-1514.

[0125] In some embodiments, the anti-Gal3 antibodies or binding fragments thereof exclude the subset of named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 38A-38D. In some embodiments, CDRs (including heavy chain CDRs and light chain CDRs), heavy chain variable regions, light chain variable regions, heavy chains, and / or light chains are excluded from the sequences associated with the subset of named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 38A-38D. In some embodiments, combinations of CDRs (including heavy chain CDRs and light chain CDRs), combinations of heavy chain variable regions, combinations of light chain variable regions, combinations of heavy chains, and / or combinations of light chains are excluded from the sequences associated with the subset of named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 38A-38D. In some embodiments, the anti-Gal3 antibody or binding fragment thereof excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38A, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38B, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38C, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38D, or excludes any one or more of its CDRs, VH, VL, HC, and / or LC.In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks the interaction between Gal3 and GLUT (e.g., GLUT1 and / or GLUT4) and excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38A, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks the interaction between Gal3 and GLUT (e.g., GLUT1 and / or GLUT4) and excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38B, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks the interaction between Gal3 and GLUT (e.g., GLUT1 and / or GLUT4) and excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38C, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks the interaction between Gal3 and GLUT (e.g., GLUT1 and / or GLUT4) and excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38D, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In other embodiments, any of these constructs are used in any of the methods provided herein.

[0126] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the subset consisting of the named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 39A-39E. In some embodiments, the CDRs (overlapping CDRs) The CDR combinations (including heavy chain CDRs and light chain CDRs), heavy chain variable regions, light chain variable regions, heavy chains, and / or light chains are selected from sequences associated with the subsets of named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 39A-39E. In some embodiments, the CDR combinations (including heavy chain CDRs and light chain CDRs), heavy chain variable region combinations, light chain variable region combinations, heavy chain combinations, and / or light chain combinations are selected from sequences associated with the subsets of named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 39A-39E. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 39A, or comprises any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 39B or comprises any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 39C or comprises any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 39D or comprises any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 39E, or comprises any one or more of their CDRs, VH, VL, HC, and / or LC.

[0127] In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to a specific epitope within the Gal3 protein, such as a Gal3 protein having the amino acid sequence of SEQ ID NO: 1-2, as provided in FIG.

[0128] In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within the peptides exemplified in Figure 18 (SEQ ID NOs: 3-26).

[0129] In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within amino acid residues 1 to 20 of SEQ ID NOs: 1 to 2. In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within amino acid residues 31 to 50 of SEQ ID NOs: 1 to 2. In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within amino acid residues 51 to 70 of SEQ ID NOs: 1 to 2. In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within amino acid residues 61 to 80 of SEQ ID NOs: 1 to 2.

[0130] In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within peptide 1 (SEQ ID NO: 3), peptide 4 (SEQ ID NO: 6), peptide 6 (SEQ ID NO: 8), or peptide 7 (SEQ ID NO: 9). In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within peptide 1 (SEQ ID NO: 3). In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 11, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within peptide 4 (SEQ ID NO: 6). In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within peptide 6 (SEQ ID NO: 8). In some embodiments, the anti-Gal3 antibody or binding fragment thereof can bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within peptide 7 (SEQ ID NO: 9). In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to an epitope presented within a region of Gal3 defined by peptide 1 (SEQ ID NO:3). In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to an epitope presented within a region of Gal3 defined by peptide 4 (SEQ ID NO:6). In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to an epitope presented within a region of Gal3 defined by peptide 6 (SEQ ID NO:8). In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to an epitope presented within a region of Gal3 defined by peptide 7 (SEQ ID NO:9).In some embodiments, the antibody binds to one, two, or all three of peptide 1, peptide 6, and / or peptide 7.

[0131] In some embodiments, an anti-Gal3 antibody or binding fragment thereof as described herein can bind to the N-terminal domain of Gal3 or a portion thereof. In some embodiments, an anti-Gal3 antibody or binding fragment thereof as described herein can bind to an epitope of Gal3 containing a GxYPG motif, where x is the amino acid alanine (A), glycine (G), or valine (V). In some embodiments, an anti-Gal3 antibody or binding fragment thereof as described herein can bind to an epitope of Gal3 containing two GxYPG motifs separated by three amino acids, where x is A, G, or V.

[0132] In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the N-terminus of Gal3, the N-terminal domain of Gal3, or the TRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the N-terminus of Gal3, the N-terminal domain of Gal3, or the TRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the C-terminus of Gal3, the C-terminal domain of Gal3, or the CRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the C-terminus of Gal3, the C-terminal domain of Gal3, or the CRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 isoform 1. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the N-terminus of Gal3 isoform 1, the N-terminal domain of Gal3 isoform 1, amino acids 1-111 of Gal3 isoform 1, the TRD of Gal3 isoform 1, or binds to amino acids 36-109 of Gal3 isoform 1. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the N-terminus of Gal3 isoform 1, the N-terminal domain of Gal3 isoform 1, amino acids 1-111 of Gal3, the TRD of Gal3 isoform 1, or amino acids 36-109 of Gal3 isoform 1. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the C-terminus of Gal3 isoform 1, the C-terminal domain of Gal3 isoform 1, amino acids 112-250 of Gal3, or the CRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the C-terminus of Gal3 isoform 1, the C-terminal domain of Gal3 isoform 1, amino acids 112-250 of Gal3, or the CRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the N-terminus of Gal3 isoform 3, the N-terminal domain of Gal3 isoform 3, amino acids 1 to 125 of Gal3, the TRD of Gal3 isoform 3, or amino acids 50 to 123 of Gal3 isoform 3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the N-terminus of Gal3 isoform 3, the N-terminal domain of Gal3 isoform 3, amino acids 1 to 125 of Gal3 isoform 3, the TRD of Gal3, or amino acids 50 to 123 of Gal3 isoform 3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to the C-terminus of Gal3 isoform 3, the C-terminal domain of Gal3 isoform 3, amino acids 126 to 264 of Gal3 isoform 3, or the CRD of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof does not bind to the C-terminal isoform 3 of Gal3, the C-terminal domain of Gal3 isoform 3, amino acids 126 to 264 of Gal3 isoform 3, or the CRD of Gal3 isoform 3.

[0133] In some embodiments, the interaction between Gal3 and a cell surface marker may be reduced to less than 80%, less than 75%, less than 70%, less than 60%, less than 59%, less than 50%, less than 40%, less than 34%, less than 30%, less than 20%, less than 14%, less than 10%, less than 7%, less than 5%, less than 4%, or less than 1%.

[0134] In some embodiments, the anti-Gal3 antibody or binding fragment thereof has a dissociation constant (K) of less than 1 nM, less than 1.2 nM, less than 2 nM, less than 5 nM, less than 10 nM, less than 13.5 nM, less than 15 nM, less than 20 nM, less than 25 nM, or less than 30 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 1 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 1.2 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 2 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 5 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 10 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 13.5 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 15 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 20 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 25 nM. D In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to Gal3 with a K of less than 30 nM. DIt binds to Gal3.

[0135] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is Complementarity-determining region 1 (V) of the heavy chain variable region exemplified in Figure 9A H In some embodiments, the anti-Gal3 antibody comprises a V-CDR1) sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 27-70. H In some embodiments, the anti-Gal3 antibody comprises a V-CDR1 sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs: 27-70. H -Contains the CDR1 sequence.

[0136] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region complementarity-determining region 2 (V HIn some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises any one of the V-CDR2) sequences (SEQ ID NOs: 71-111, 801, 951, 952) having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 71-111, 801, 951, 952. H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V-CDR2 sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs: 71-111, 801, 951, and 952. H - Contains the CDR2 sequence.

[0137] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region complementarity-determining region 3 (V ) of the heavy chain variable region as illustrated in FIG. 19C . HIn some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises any one of the V-CDR3) sequences (SEQ ID NOs: 112-169, 802, 953, 954) having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 112-169, 802, 953, 954. H In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V-CDR3 sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs: 112-169, 802, 953, and 954. H -Contains CDR3 sequences.

[0138] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain variable region complementarity-determining region 1 (V ) of the light chain variable region illustrated in FIG. 20A . LIn some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises any one of the V-CDR1) sequences (SEQ ID NOs: 170-220) having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 170-220. L In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V-CDR1 sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs: 170-220. L -Contains the CDR1 sequence.

[0139] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain variable region complementarity-determining region 2 (V L In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises any one of the V-CDR2) sequences (SEQ ID NOs: 221-247) having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 221-247. LIn some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V-CDR2 sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs: 221-247. L - Contains the CDR2 sequence.

[0140] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain variable region complementarity-determining region 3 (V ) of the light chain variable region as illustrated in FIG. 20C . L In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises any one of the V-CDR3) sequences (SEQ ID NOs: 248-296) having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs: 248-296. L In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a CDR3 sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to any one of SEQ ID NOs: 248-296. V with at least 99% sequence similarity L-Contains CDR3 sequences.

[0141] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region (V H ) and the light chain variable region (V L In some embodiments, the V H is V selected from any of Figures 19A to 19C H -CDR1, V H CDR2, and / or V H In some embodiments, the V L is V selected from any of Figures 20A to 20C L -CDR1, V L CDR2, and / or V L In some embodiments, the anti-Gal3 antibody or binding fragment thereof may comprise a V-CDR3 as illustrated in Figures 21 and 22. H CDRs and V in the sequence L The CDRs in the sequence are included.

[0142] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region (V) selected from Figure 21. H ) sequence (SEQ ID NOS: 297-373, 803, 806-820, 940, 955-968, 1067-1109, 1415-1439). In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOS: 297-373, 803, 806-820, 940, 955-968, 1067-1109, 1415-1439. HIn some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs: 297-373, 803, 806-820, 940, 955-968, 1067-1109, and 1415-1439. H Contains arrays.

[0143] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain variable region (V) selected from Figure 22. L ) sequence (SEQ ID NOS: 374-447, 821-835, 941-943, 969-982, 1110-1152, 1440-1464). In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOS: 374-447, 821-835, 941-943, 969-982, 1110-1152, 1440-1464. LIn some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a VL sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, and 1440-1464.

[0144] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a combination of heavy and light chain variable regions as illustrated in FIG.

[0145] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain sequence and a light chain sequence as illustrated in FIG. 25 (SEQ ID NOs: 448-538, 804-805, 836-865, 983-1010, 1153-1238, 1465-1514).

[0146] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19 D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F84 6C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F1 0, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849 C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846 .2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B 11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 84 7.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847 .4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D 10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.and 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or a binding fragment thereof.

[0147] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B 10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C. 2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F8 47C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 8 46.2B11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T .2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 8 47.15F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 8 49.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C. 21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C 4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D1 0-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, Comprising, consisting essentially of, or consisting of 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or a binding fragment thereof.

[0148] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19 D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F84 6C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F1 0, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849 C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846 .2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B 11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 84 7.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847 .4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D 10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、20H5.A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v2-QDT、2D10-hVH1-hVL1、2D10-hVH1-hVL2、 2D10-hVH1-hVL3、2D10-hVH1-hVL4、2D10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL4、20H5.A3-hIgG4(S228P)、20H5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0mL1、798-9.20H5.A3-mH1mL0、79. 8-9.20H5.A3-mH1mL1、798-9.20H5.A3-mH2mL0、798-9.20H5.A3-mH2mL1、20H5.A3-VH1VL1、20H5.A3-VH1VL2、20H5.A3-VH1VL3、20H5.A3-VH1VL4、20H5.A3-VH1VL5、20H5.A3-VH1VL6、20H5.A3-VH2VL3、20H5.A3-VH2 VL4、20H5.A3-VH2VL5、20H5.A3-VH2VL6、20H5.A3-VH3VL5、20H5.A3-VH3VL6、20H5.A3-VH4VL3、20H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3-VH5VL5、20H5.A3-VH5VL6、20H5.A3-VH6VL4、20H5.A3- VH6VL5、20H5.A3-VH6VL6、20H5.A3-VH7VL1、20H5.A3-VH7VL2、20H5.A3-VH7VL3、20H5.A3-VH7VL4、20H5.A3-VH7VL5、20H5.A3-VH7VL6、20H5.A3_hVH3VL1-hIgG1(KEMv2)、20H5.A3_hVH3VL1-hIgG1(LALAPGv2)、20H5 .A3_hVH3VL1-hIgG1(REM)、20H5.A3_hVH5VL1-hIgG1(KEMv2)、20H5.A3_hVH5VL1-hIgG1(LALAPGv2)、20H5.A3_hVH5VL1-hIgG1(REM)、20H5.A3_hVH6VL1-hIgG1(KEMv2)、20H5.A3_hVH6VL1-hIgG1(LALAPGv2)、20H5.A3_hVH6VL1-hIgG1(REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21 H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H and 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0149] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 1 3H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846 TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B 11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847. 11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849 .4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.1 2C4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3、2D10-hVH3-HVL4、20H5.A3-VH3VL1、20H5.A3-VH3VL3、20H5.A3-VH4VL1、20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、20H5 .A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v2-QDT、2D10-hVH1-hVL1、2D10 -hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-hVL4、2D10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL4、20H5.A3-hIgG4(S228P)、20H 5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0mL1、798-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1mL1、798-9.20H5.A3-mH2mL0、798-9.20H5.A3-mH2mL 1、20H5.A3-VH1VL1、20H5.A3-VH1VL2、20H5.A3-VH1VL3、20H5.A3-VH1VL4、20H5.A3-VH1VL5、20H5.A3-VH1VL6、20H5.A3-VH2VL3、20H5.A3-VH2VL4、20H 5.A3-VH2VL5、20H5.A3-VH2VL6、20H5.A3-VH3VL5、20H5.A3-VH3VL6、20H5.A3-VH4VL3、20H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3- VH5VL5、20H5.A3-VH5VL6、20H5.A3-VH6VL4、20H5.A3-VH6VL5、20H5.A3-VH6VL6、20H5.A3-VH7VL1、20H5.A3-VH7VL2、20H5.A3-VH7VL3、20H5.A3-VH7VL 4、20H5.A3-VH7VL5、20H5.A3-VH7VL6、20H5.A3_hVH3VL1-hIgG1(KEMv2)、20H5.A3_hVH3VL1-hIgG1(LALAPGv2)、20H5.A3_hVH3VL1-hIgG1(REM)、20H5.A3_hVH5VL1-hIgG1(KEMv2), 20H5.A3_hVH5VL1-hIgG1(LALAPGv2), 20H5.A3_hVH5VL1-hIgG1(REM), 20H5.A3_hVH6VL1-hIgG1(KEMv2), 20H 5.A3_hVH6VL1-hIgG1(LALAPGv2), 20H5.A3_hVH6VL1-hIgG1(REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1 , 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0150] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises one or more heavy chain variable region CDRs shown in Figures 19A-19C. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises one or more light chain variable region CDRs shown in Figures 20A-20C. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region shown in Figure 21. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain variable region shown in Figure 22. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a combination of heavy and light chain variable regions shown in Figure 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain and / or light chain shown in Figure 25. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises any one of Figures 19A-19C, 20A-20C, 21, 22, 23, 24, and 25. or more of the sequences provided herein, or any one or more of the sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identity thereto. In some embodiments, the anti-Gal3 antibody or binding fragment thereof may consist of or comprise any one or more of the sequences provided in any one or more of Figures 19A-19C, 20A-20C, 21, 22, 23, 24, and 25, or any one or more sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more similarity thereto.

[0151] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: (1) V H -CDR1, V H -CDR2, and V H a heavy chain variable region comprising CDR3; and (2) V L -CDR1, V L -CDR2, and V L In some embodiments, the V H - CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 32, 37, or 66. In some embodiments, the V H- CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 801, 951, 952, 77, or 108. In some embodiments, the V H - CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 953, 954, 802, 118, or 164. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 171, 178, or 215. In some embodiments, the V L - CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 222, 229, or 225. In some embodiments, the V L - CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 257, 256, or 291.

[0152] In some embodiments, the heavy chain variable region comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 806-820, 955-968, 1067-1109, and 1415-1439. In some embodiments, the light chain variable region has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 821-835, 969-982, 1110-1152, and 1440-1464. Contains amino acid sequences with 0.00% identity.

[0153] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 851-865, 997-1010, 1196-1238, 1412, and 1490-1514.

[0154] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 20H5.A3, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or a binding fragment thereof.

[0155] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is 20H5.A3, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, 20H5.A3-hIgG4(S228P), 20H5.A3-hIgG4(S228P)-mv2, 798-9.20H5.A3-mH1mL1, 798-9.20H5.A3-mH1mL0, 798-9.20H5.A3-mH1mL1, 798-9.20H5.A3-mH1mL1, 798-9.20H5.A3-mH1mL2, 798-9.20H5.A3-mH1mL3 ...1, 798-9.20H5.A3-m A3-mH1mL1, 798-9.20H5.A3-mH2mL0, 798-9.20H5.A3-mH2mL1, 20H5.A3-VH 1VL1, 20H5.A3-VH1VL2, 20H5.A3-VH1VL3, 20H5.A3-VH1VL4, 20H5.A3-VH1V L5, 20H5.A3-VH1VL6, 20H5.A3-VH2VL3, 20H5.A3-VH2VL4, 20H5.A3-VH2VL5 , 20H5.A3-VH2VL6, 20H5.A3-VH3VL5, 20H5.A3-VH3VL6, 20H5.A3-VH4VL3, 20 H5.A3-VH4VL4, 20H5.A3-VH4VL5, 20H5.A3-VH4VL6, 20H5.A3-VH5VL5, 20H5 .A3-VH5VL6, 20H5.A3-VH6VL4, 20H5.A3-VH6VL5, 20H5.A3-VH6VL6, 20H5.A 3-VH7VL1, 20H5.A3-VH7VL2, 20H5.A3-VH7VL3, 20H5.A3-VH7VL4, 20H5.A3- VH7VL5, 20H5.A3-VH7VL6, 20H5.A3_hVH3VL1-hIgG1(KEMv2), 20H5.A3_hVH3 VL1-hIgG1(LALAPGv2), 20H5.A3_hVH3VL1-hIgG1(REM), 20H5.A3_hVH5VL1-hIgG1(KEMv2), 20H5.A3_hVH5VL1-hIgG1(LALAPGv2), 20H5.A3_hVH5VL1-hIgG1(REM), 20H5.A3_hVH6VL1-hIgG1(KEMv2), 20H5.A3_hVH6VL1-hIgG1(LALAPGv2), 20H5.A3_hVH6VL1-hIgG1(REM), or a binding fragment thereof.

[0156] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, and 2D10-hVH3. -HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, or a binding fragment thereof.

[0157] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 2D10.2B2-v2, 2D10-VH0-NDA-VL0, 2D10-VH 0-QDT-VL0, 2D10-VH0-SDT-VL0, 2D10-VH0-v1-QDT, 2D10-VH0-v2-QDT, 2D10-hVH1-hVL1, 2D10-hVH1-hVL2, 2D10-hVH1-hVL3, 2D10-hVH1-hVL4, 2D10-hVH2-hVL1, 2D10-hVH2-hVL2, 2D10-hVH2-hVL3, 2D10-hVH2-hVL4, or a binding fragment thereof.

[0158] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0159] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a humanized antibody or binding fragment thereof. In other cases, the anti-Gal3 antibody or binding fragment thereof comprises a chimeric antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody comprises a full-length antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a bispecific antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a monovalent Fab', a bivalent Fab2, a single-chain variable fragment (scFv), a diabody, a minibody, a nanobody, a single-domain antibody (sdAb), or a camelid antibody or binding fragment thereof.

[0160] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is a bispecific antibody or binding fragment thereof. Exemplary bispecific antibody formats include Knobs-into-Holes (KiH), Asymmetric Re-engineering Technology-immunoglobulin (ART-Ig), Triomab quadroma, bispecific monoclonal antibody (BiMAb, BsmAb, BsAb, bsMab, BS-Mab, or Bi-MAb), Azymetric, Biclonics, Fab-scFv-Fc, Two-in-one / Dual Action Fab (DAF), FinomAb, scFv-Fc-(Fab) fusion, Dock-aNd-Lock (DNL), tandem diabody (TandAb), Dual-affinity-ReTargeting (DART), nanobody, triplebody, tandem scFv (taFv), triple head (triple head), and Fab-scFv-Fc-(Fab) fusion. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is a tetravalent dAb / VHH, including, but not limited to, a tandem dAb / VHH, a triple dAb / VHH, or a tetravalent dAb / VHH. ann, "The making of bispecific antibodies," MABS 9(2): 182-212 (2017), including bispecific antibody formats exemplified in the publication.

[0161] In some embodiments, the anti-Gal3 antibody or binding fragment thereof may comprise an IgM, IgG (e.g., IgG1, IgG2, IgG3, or IgG4), IgA, or IgE framework. The IgG framework may be IgG1, IgG2, IgG3, or IgG4. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises an IgG1 framework. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises an IgG2 framework. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises an IgG4 framework. The anti-Gal3 antibody or binding fragment thereof may further comprise Fc mutations.

[0162] In some embodiments, the Fc region comprises one or more mutations that modulate Fc-receptor interactions, thereby enhancing effector function, e.g., ADCC and / or CDC. In such cases, exemplary residues that modulate effector function when mutated include S239, K326, A330, I332, or E333, where the residue positions correspond to IgG1 and the residue numbering is according to Kabat numbering (Kabat et al. 1991, EU Index of Sequences of Proteins of Immunological Interest). In some embodiments, the one or more mutations comprise S239D, K326W, A330L, I332E, E333A, E333S, or a combination thereof. In some embodiments, the one or more mutations comprise S239D, I332E, or a combination thereof. In some embodiments, the one or more mutations comprise S239D, A330L, I332E, or a combination thereof. In some embodiments, the one or more mutations comprise K326W, E333S, or a combination thereof. In some embodiments, the mutation comprises E333A.

[0163] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a humanization score of greater than 70, greater than 80, greater than 81, greater than 82, greater than 83, greater than 84, greater than 85, greater than 86, greater than 87, greater than 88, greater than 89, greater than 90, or greater than 95. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a humanization score of greater than 80. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a humanization score of greater than 83. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a humanization score of greater than 85. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a humanization score of greater than 87. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a humanization score of greater than 90. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain humanization score of greater than 70, greater than 80, greater than 81, greater than 82, greater than 83, greater than 84, greater than 85, greater than 86, greater than 87, greater than 88, greater than 89, greater than 90, or greater than 95, optionally greater than 80, 85, or greater than 87. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain humanization score of greater than 70, greater than 80, greater than 81, greater than 82, greater than 83, greater than 84, greater than 85, greater than 86, greater than 87, greater than 88, greater than 89, greater than 90, or greater than 95, optionally greater than 80, 83, or greater than 85.

[0164] Also disclosed herein are proteins. In some embodiments, the proteins comprise one or more of SEQ ID NOs: 27-538, 801-865, 955-1010, 1067-1238, and 1415-1514. In some embodiments, the proteins comprise one or more of SEQ ID NOs: 27-538, 801-865, 955-1010, 1067-1238, and 1415-1514. In some embodiments, the protein comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one or more of SEQ ID NOs: 27-538, 801-865, 955-1010, 1067-1238, 1415-1514. In some embodiments, the protein comprises a sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to any one or more of SEQ ID NOs: 27-538, 801-865, 955-1010, 1067-1238, 1415-1514. In some embodiments, the protein comprises six sequences selected from each of SEQ ID NOs: 27-70; SEQ ID NOs: 71-111, 801, 951, 952; SEQ ID NOs: 112-169, 802, 953, 954; SEQ ID NOs: 170-220; SEQ ID NOs: 221-247; and SEQ ID NOs: 248-296. In some embodiments, the protein comprises two sequences selected from each of SEQ ID NOs: 279-373, 803, 806-820, 955-968, 1067-1190, 1415-1439, and SEQ ID NOs: 374-447, 821-835, 969-982, 1110-1152, and 1440-1464. In some embodiments, the protein comprises two sequences selected from each of SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1465-1489, and SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1490-1514. In some embodiments, the protein comprises any one or more of the sequences depicted in Figures 19A-19C, 20A-20C, 21, 22, 23, 24, and 25.

[0165] In some embodiments, the protein comprises one or more sequences defined by a consensus sequence. The consensus sequences provided herein were obtained from the alignment of the CDRs shown in Figures 37A-37B. However, it is contemplated that alternative alignments may be performed (e.g., using global or local alignments, or by various algorithms such as hidden Markov models, seed-guided trees, the Needleman-Wunsch algorithm, or the Smith-Waterman algorithm), and that alternative consensus sequences may be obtained.

[0166] In some embodiments, the protein has the formula X1X2X3X4X5X6X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 X 17 X1 is no amino acid, or R; X2 is no amino acid, or S; X3 is no amino acid, S, or T; X4 is no amino acid, E, G, K, Q, or R; X5 is no amino acid, A, D, G, I, N, or S; X6 is no amino acid, I, L, or V; X7 is no amino acid, F, L, S, or V; X8 is no amino acid, D, E, H, N, S, T, or Y; X9 is no amino acid, D, E, I, K, N, R, S, T, or V; 10 is no amino acid, D, H, N, R, S, or Y; X 11 is no amino acid, A, G, N, S, T, or V; X 12 is no amino acid, A, I, K, N, Q, T, V, or Y; X 13 is no amino acid, D, G, H, K, N, S, T, or Y; X 14 is no amino acid, C, F, I, N, S, T, V, or Y; X 15 is no amino acid, D, L, N, W, or Y; X 16is no amino acid, N, or D; X 17 is no amino acid, or D. In some embodiments, the protein comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the protein comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0167] In some embodiments, the protein comprises a sequence defined by the formula X1X2X3X4X5X6X7X8, where X1 is no amino acid, K, L, N, Q, or R; X2 is no amino acid, A, L, M, or V; X3 is no amino acid, C, K, or S; X4 is no amino acid or T; X5 is no amino acid, A, E, F, G, H, K, Q, R, S, W, or Y; X6 is no amino acid, A, G, or T; X7 is no amino acid, I, K, N, S, or T; and X8 is no amino acid, N, or S. In some embodiments, the protein comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the consensus sequence, hi some embodiments, the protein comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from the consensus sequence.

[0168] In some embodiments, the protein has the formula X1X2X3X4X5X6X7X8X9X 10X1 is no amino acid, A, E, F, H, L, M, Q, S, V, or W; X2 is A, H, or Q; X3 is D, F, G, H, L, M, N, Q, S, T, W, or Y; X4 is no amino acid or W; X5 is A, D, I, K, L, N, Q, R, S, T, V, or Y; X6 is D, E, H, I, K, L, N, Q, S, or T; X7 is D, F, K, L, N, P, S, T, V, W, or Y; X8 is H, P, or S; X9 is F, L, P, Q, R, T, W, or Y; 10 are no amino acids, T, or V. In some embodiments, the protein comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the protein comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0169] In some embodiments, the protein has the formula X1X2X3X4X5X6X7X8X9X 10 X is E, G, or R; X is F, N, or Y; X is A, I, K, N, S, or T; X is F, I, or L; X is I, K, N, R, S, or T; X is D, G, I, N, S, or T; X is F, G, H, S, or Y; X is no amino acid, A, D, G, I, M, N, T, V, W, or Y; X is no amino acid, M, or Y; 10is no amino acid or G; in some embodiments, the protein comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the protein comprises a sequence with 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0170] In some embodiments, the protein has the formula X1X2X3X4X5X6X7X8X9X 10 X1 is no amino acid, I, or L; X2 is no amino acid, or R; X3 is no amino acid, F, I, L, or V; X4 is A, D, F, H, K, L, N, S, W, or Y; X5 is A, D, P, S, T, W, or Y; X6 is D, E, G, H, K, N, S, V, or Y; X7 is D, E, G, N, S, or T; X8 is D, G, I, K, N, Q, R, S, V, or Y; X9 is A, D, E, G, I, K, N, P, S, T, V, or Y; 10 is no amino acid, I, P, S, or T. In some embodiments, the protein has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104 In some embodiments, the protein comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from the consensus sequence.

[0171] In some embodiments, the protein has the formula X1X2X3X4X5X6X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 X 17 X18 X 19 X 20 X 21 X 22 X 23 X 24 X 25 X1 is no amino acid, or A; X2 is no amino acid, A, R, or Y; X3 is no amino acid, A, F, H, K, L, R, S, or V; X4 is no amino acid, A, D, K, N, R, S, or T; X5 is no amino acid, A, D, G, H, I, L, N, P, R, S, T, V, or Y; X6 is no amino acid, A, D, G, H, K, N, P, Q, R, S, or Y; X7 is no amino acid, D, F, G, H, P, R, S, W, or Y; X8 is no amino acid, A, D, E, G, I, R, or S; X9 is no amino acid, A, C, D, E, F, G, I, N, R, S, T, V, or Y; X 10 is no amino acid, A, D, M, P, R, S, T, V, or Y; X 11 is no amino acid, A, D, E, F, L, T, V, or Y; X 12 is no amino acid, A, G, L, M, R, or T; X 13 is no amino acid, A, D, E, F, G, R, S, T, or V; X 14 is no amino acid, A, D, G, L, P, Q, R, S, T, V, or Y; X 15 is no amino acid, A, D, G, N, S, V, W, or Y; X 16 is no amino acid, A, D, E, F, L, P, T, V, W, or Y; X 17 is no amino acid, F, I, L, M, R, or Y; X 18 is no amino acid, A, D, G, N, or T; X 19 is no amino acid, F, N, S, T, V, or Y; X 20 is no amino acid or L; X 21 is no amino acid or A; X 22 is no amino acid or W; X 23 is no amino acid or F; X 24is no amino acid or A; X 25 is no amino acid, or Y. In some embodiments, the protein comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the protein comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0172] Pharmaceutical preparations Pharmaceutical preparations for treating diseases such as those described herein may include the anti-Gal3 antibody or its binding fragment. The anti-Gal3 antibody or its binding fragment may be formulated for systemic administration. Alternatively, the anti-Gal3 antibody or its binding fragment may be formulated for parenteral administration.

[0173] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is formulated as a pharmaceutical composition for administration to a subject by, but not limited to, parenteral (e.g., intravenous, subcutaneous, intramuscular, intraarterial, intradermal, intraperitoneal, intravitreal, intracerebral, or intracerebroventricular), oral, intranasal, buccal, rectal, or transdermal routes of administration. In some cases, the pharmaceutical compositions described herein are formulated for parenteral (e.g., intravenous, subcutaneous, intramuscular, intraarterial, intradermal, intraperitoneal, intravitreal, intracerebral, or intracerebroventricular) administration. In other cases, the pharmaceutical compositions described herein are formulated for systemic administration. In other cases, the pharmaceutical compositions described herein are formulated for oral administration. In still other cases, the pharmaceutical compositions described herein are formulated for intranasal administration.

[0174] In some cases, the pharmaceutical composition further comprises a pH adjusting or buffering agent, such as acids, such as acetic acid, boric acid, citric acid, lactic acid, phosphoric acid, and hydrochloric acid; sodium hydroxide, sodium phosphate; and buffers such as citrate / sugar, sodium bicarbonate, and ammonium chloride. Such acids, bases, and buffers are included in amounts necessary to maintain the pH of the composition within an acceptable range.

[0175] In some cases, the pharmaceutical composition contains one or more salts in an amount necessary to bring the osmolality of the composition into an acceptable range. Such salts include salts having sodium, potassium, or ammonium cations and chloride, citrate, ascorbate, borate, phosphate, bicarbonate, sulfate, thiosulfate, or bisulfite anions; suitable salts include sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfite, and ammonium sulfate.

[0176] In some cases, the pharmaceutical composition further comprises a diluent that is used to stabilize the compound, because the diluent can create a more stable environment.Salt dissolved in a buffer solution (which can also adjust or maintain pH) is used as a diluent in the art, including but not limited to phosphate buffered saline.In some cases, the diluent increases the volume of the composition, making it easier to compress or providing sufficient volume for homogeneous mixing for capsule filling. Such compounds may include, for example, lactose, starch, mannitol, sorbitol, glucose, microcrystalline cellulose such as Avicel®; calcium hydrogen phosphate, dicalcium phosphate dihydrate; tricalcium phosphate, calcium phosphate; anhydrous lactose, spray-dried lactose; pregelatinized starch, compressible sugars such as Di-Pac® (Amstar); mannitol, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate stearate, sucrose-based diluents, powdered sugar; monobasic calcium sulfate monohydrate, calcium sulfate dihydrate; calcium lactate trihydrate, dextrates; hydrolyzed cereal solids, amylose; powdered cellulose, calcium carbonate; glycine, kaolin; mannitol, sodium chloride; inositol, bentonite, and the like.

[0177] In some embodiments, the pharmaceutical formulations include, but are not limited to, aqueous dispersions, self-emulsifying dispersions, solid solutions, liposomal dispersions, aerosols, solids, powders, immediate release formulations, sustained release formulations, fast dissolving formulations, tablets, capsules, pills, delayed release formulations, extended release formulations, pulsed release formulations, multiparticulate formulations (e.g., nanoparticle formulations), and mixed immediate and sustained release formulations.

[0178] In some cases, the pharmaceutical formulation may further comprise an additional therapeutic agent. Non-limiting examples of additional therapeutic agents include alpha-glucosidase inhibitors, including acarbose (Precose®) and miglitol (Glyset®); metformin-alogliptin (Kazano®), metformin-canagliflozin (Invokamet®), metformin-dapagliflozin (Xigduo® XR), metformin-empagliflozin (Synjardy®), metformin-glipizide, metformin-glyburide (Glucovance®), and others. biguanides, including metformin-linagliptin (Jentadueto®), metformin-pioglitazone (Actoplus®), metformin-repaglinide (PrandiMet®), metformin-rosiglitazone (Avandamet®), metformin-saxagliptin (Kombiglyze® XR), and metformin-sitagliptin (Janumet®); dopamine agonists, including bromocriptine (Cycloset®); alogliptin (Nesina®), alogliptin-metformin (Kazano®), alogliptin-pioglitazone (Oseni®), linagliptin (Tradjenta®), linagliptin-empagliflozin (Glyxambi®), linagliptin-metformin (Jentadueto®), saxagliptin (Onglyza®), saxagliptin-metformin (Kombiglyze®), dipeptidyl peptidase-4 (DPP-4) inhibitors, including sitagliptin (Januvia®), sitagliptin-metformin (Janumet®, and Janumet® XR), and sitagliptin and simvastatin (Juvisync®); albiglutide (Tanzeum®), dulaglutide (Trulicity®), exenatide (Byetta®), extended-release exenatide (Byetta®), glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists), including ureon®, and liraglutide (Victoza®), semaglutide (Ozempic®); meglitinides, including nateglinide (Starlix®), repaglinide (Prandin®), and repaglinide-metformin (Prandimet®); dapagliflozin (Farxiga®), dapagliflozin-metformin sodium-glucose transporter (SGLT) 2 inhibitors, including (Xigduo® XR), canagliflozin (Invokana®), canagliflozin-metformin (Invokamet®), empagliflozin (Jardiance®), empagliflozin-linagliptin (Glyxambi®), empagliflozin-metformin (Synjardy®), and ertugliflozin (Steglatro®);Sulfonylureas, including glimepiride (Amaryl®), glimepiride-pioglitazone (Duetact®), glimepiride-rosiglitazone (Avandaryl®), gliclazide, glipizide (Glucotrol®), glipizide-metformin (Metaglip®), glyburide (DiaBeta®, Glynase®, Micronase®), glyburide-metformin (Glucovance®), chlorpropamide (Diabinese®), tolazamide (Tolinase®), and tolbutamide (Orinase®, Tol-Tab®); rosiglitazone (Avandia®), rosiglitazone-glimepiride (Avandaryl®), rosiglitazone-metformin (Amaryl®), Thiazolidinediones, including pioglitazone (Actos®), pioglitazone-alogliptin (Oseni®), pioglitazone-glimepiride (Duetact®), pioglitazone-metformin (Actoplus Met®, Actoplus Met® XR);

[0179] Example Usage Any of the above anti-Gal3 antibodies or binding fragments thereof, or proteins may be used in the methods provided herein.

[0180] In some embodiments, a method of enhancing glucose transporter (GLUT) translocation in a cell is disclosed. The method comprises contacting the cell with an anti-Gal3 antibody or binding fragment thereof. In some embodiments, binding of the anti-Gal3 antibody or binding fragment thereof to Gal3 in the cell inhibits blockage of Gal3-mediated GLUT translocation. In some embodiments, the glucose transporter is glucose transporter 1 (GLUT1) and / or glucose transporter 4 (GLUT4). In some embodiments, the method is performed in vitro or in vivo. In some embodiments, In some embodiments, GLUT translocation in cells is enhanced by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% after contact with the anti-Gal3 antibody or binding fragment thereof, compared to cells not contacted with the anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof selectively binds to the N-terminal domain of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to peptide 1 (SEQ ID NO: 3), peptide 6 (SEQ ID NO: 8), or peptide 7 (SEQ ID NO: 9), or any combination thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to (1) V H -CDR1, V H -CDR2, and V H a heavy chain variable region comprising CDR3; and (2) V L -CDR1, V L -CDR2, and V L In some embodiments, the V H- CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 27-70. H -CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 71-111, 801, 951, and 952. In some embodiments, the V H -CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 112-169, 802, 953, and 954. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220. L - CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 221-247. L- CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 248-296. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, and V L In some embodiments, the heavy chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, and 1415-1439. In some embodiments, the light chain variable region has a sequence identity of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98% of a sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, and 1440-1464. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, and 1490-1514. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19 D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F84 6C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F1 0, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849 C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846 .2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B 11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 84 7.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847 .4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D 10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、20H5.A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1- QDT、2D10-VH0-v2-QDT、2D10-hVH1-hVL1、2D10-hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-hVL4、2D10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-h VH2-hVL4、20H5.A3-hIgG4(S228P)、20H5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0mL1、798-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1mL1、798-9.20H5.A 3-mH2mL0、798-9.20H5.A3-mH2mL1、20H5.A3-VH1VL1、20H5.A3-VH1VL2、20H5.A3-VH1VL3、20H5.A3-VH1VL4、20H5.A3-VH1VL5、20H5.A3-VH1VL6、20H5.A3-VH. 2VL3, 20H5.A3-VH2VL4, 20H5.A3-VH2VL5, 20H5.A3-VH2VL6, 20H5.A3-VH3VL5, 20H5.A3-VH3VL6, 20H5.A3-VH4VL3, 20H5.A3-VH4VL4, 20H5.A3-VH4VL5, 20H5.A3-VH4VL6, 20H5.A3-VH5VL5, 20H5.A3-VH5VL6, 20H5.A3-VH6VL4, 20H5.A3-VH6VL5, 20H5.A3-VH6 VL6、20H5.A3-VH7VL1、20H5.A3-VH7VL2、20H5.A3-VH7VL3、20H5.A3-VH7VL4、20H5.A3-VH7VL5、20H5.A3-VH7VL6、20H5.A3_hVH3VL1-hIgG1(KEMv2)、20H5.A3_hVH3VL1-hIgG1(LALAPGv2)、20H5.A3_hVH3VL1-hIgG1(REM)、20H5.A3_hVH5VL1-hIgG1(KEMv2)、2 0H5.A3_hVH5VL1-hIgG1(LALAPGv2)、20H5.A3_hVH5VL1-hIgG1(REM)、20H5.A3_hVH6VL1-hIgG1(KEMv2)、20H5.A3_hVH6VL1-hIgG1(LALAPGv2)、20H5.A3_hVH6VL1-hIgG1(REM)、21H6-H0L0、21H6-H1L1、21H6-H1L2、21H6-H1L3、21H6-H1L4、21H6-H2L1、21H6- H2L2、21H6-H2L3、21H6-H2L4、21H6-H3L1、21H6-H3L2、21H6-H3L3、21H6-H3L4、21H6-H4L1、21H6-H4L2、21H6-H4L3、21H6-H4L4、2 1H6-H5L1、21H6-H5L2、21H6-H5L3、21H6-H5L4、21H6-H6L1、21H6 -H6L2, 21H6-H6L3, 21H6-H6L4,In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 20H5.A3, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0181] In some embodiments, a method for enhancing glucose transporter (GLUT) translocation in a cell is disclosed. The method comprises contacting a cell with a pre-incubated complex of Gal3 and an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the pre-incubated complex of Gal3 and the anti-Gal3 antibody or binding fragment thereof comprises a 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, or 1:2.5 mass ratio of Gal3 and the anti-Gal3 antibody or binding fragment thereof, or approximately such a mass ratio, or any mass ratio within a range defined by any two of the above mass ratios. It is made by In some embodiments, the pre-incubation of Gal3 with the anti-Gal3 antibody or binding fragment thereof to form a complex comprises Gal3 at, or about, a concentration of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 μg / mL, or any concentration within a range defined by any two of the above concentrations. 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 , 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 μg / mL, or at about that concentration, or any concentration within a range defined by any two of the above concentrations. In some embodiments, the glucose transporter is glucose transporter 1 (GLUT1) and / or glucose transporter 4 (GLUT4). In some embodiments, the method is performed in vitro or in vivo.In some embodiments, GLUT translocation in cells is enhanced by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% after contacting cells with a complex preincubated with Gal3 and an anti-Gal3 antibody or binding fragment thereof, compared to cells not contacted with a complex preincubated with Gal3 and an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof selectively binds to the N-terminal domain of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to peptide 1 (SEQ ID NO: 3), peptide 6 (SEQ ID NO: 8), or peptide 7 (SEQ ID NO: 9), or any combination thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to (1)V. H -CDR1, V H -CDR2, and V H a heavy chain variable region comprising CDR3; and (2) V L -CDR1, V L -CDR2, and V L In some embodiments, the V H - CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 27-70. H-CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 71-111, 801, 951, and 952. In some embodiments, the V H -CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 112-169, 802, 953, and 954. In some embodiments, the V L -CDR1 is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of the amino acid sequences of SEQ ID NOs: 170 to 220. In some embodiments, the V L - CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 221-247. L - CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 248-296. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V H -CDR1, V H -CDR2, V H -CDR3, VL -CDR1, V L -CDR2, and V L In some embodiments, the heavy chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, and 1415-1439. In some embodiments, the light chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, and 1440-1464. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, and 1490-1514. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H1L2, 4A11.H1L3, 4A11.H1L4, 4A11.H1L5, 4A11.H1L6, 4A11.H1L7, 4A11.H1L8, 4A11.H1L9, 4A11.H1L9, 4A11.H1L9, 4A11.H1L9, 4A11.H1L1 ... .H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D 12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.1 6B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8 H3, 846.2B11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E 11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11, 847 .27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 8 49.8D12、F847C.21H6、849.5H1、847.23F11、847.16D10、847.13E2-mH0mL 1、847.13E2-mH0mL2、847.12C4、847.4D3、2D10-VH0-VL0、2D10-hVH4-HVL1 、2D10-hVH4-HVL2、2D10-hVH4-HVL3、2D10-hVH4-HVL4、2D10-hVH3-HVL1、2D10-hVH3-HVL2、2D10-hVH3-HVL3、2D10-hVH3-HVL4、20H5.A3-VH3VL1、20H 5.A3-VH3VL3、20H5.A3-VH4VL1、20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、20H5.A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0 -QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v2-QDT、2D10-hVH1-hVL1、2D10-hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-hVL4、2D10-h VH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL4、20H5.A3-hIgG4(S228P)、20H5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0mL1、79 8-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1mL1、798-9.20H5.A3-mH2mL0、798-9.20H5.A3-mH2mL1、20H5.A3-VH1VL1、20H5.A3-VH1VL2、20H5.A3-VH1V L3、20H5.A3-VH1VL4、20H5.A3-VH1VL5、20H5.A3-VH1VL6、20H5.A3-VH2VL3、20H5.A3-VH2VL4、20H5.A3-VH2VL5、20H5.A3-VH2VL6、20H5.A3-VH3VL5、2 0H5.A3-VH3VL6、20H5.A3-VH4VL3、20H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3-VH5VL5、20H5.A3-VH5VL6、20H5.A3-VH6VL4、20H5.A3-VH6VL5, 20H5.A3-VH6VL6, 20H5.A3-VH7VL1, 20H5.A3-VH7VL2, 20H5.A3-VH7VL3, 20H5.A3-VH7V L4, 20H5.A3-VH7VL5, 20H5.A3-VH7VL6, 20H5.A3_hVH3VL1-hIgG1(KEMv2), 20H5.A3_hVH3VL1-hIgG 1(LALAPGv2), 20H5.A3_hVH3VL1-hIgG1(REM), 20H5.A3_hVH5VL1-hIgG1(KEMv2), 20H5.A3_hVH5VL 1-hIgG1(LALAPGv2), 20H5.A3_hVH5VL1-hIgG1(REM), 20H5.A3_hVH6VL1-hIgG1(KEMv2), 20H5.A3_ hVH6VL1-hIgG1(LALAPGv2), 20H5.A3_hVH6VL1-hIgG1(REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 2 1H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is 20H5.A3, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, or a combination thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0182] In some embodiments, antibodies that bind to the N-terminal domain (NTD) of Gal3 (e.g., TB001, TB006, 2D10-VH0-VL0, 20H5.A3) can be used to reduce the ability of Gal3 to block GLUT (e.g., GLUT1 and / or GLUT4) translocation. In some embodiments, any antibody having one to six of the CDRs provided herein that binds to the NTD can be used in this manner or for this purpose. In some embodiments, reducing the ability of Gal3 to block GLUT (e.g., GLUT1 and / or GLUT4) translocation can be beneficial for treating, ameliorating, or preventing diseases or disorders such as insulin resistance syndrome, type 2 diabetes, chronic hyperinsulinemia, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome, obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, pancreatic cancer-associated diabetes, or cancer.

[0183] In some embodiments, antibodies that bind to the carbohydrate recognition binding domain (CRD) of Gal3 (e.g., 13E2) can be used to enhance the ability of Gal3 to block GLUT (e.g., GLUT1 and / or GLUT4) translocation. In some embodiments, any antibody having one to six of the CDRs provided herein that binds to the CRD can be used in this manner or for this purpose. In some embodiments, enhancing the ability of Gal3 to block GLUT (e.g., GLUT1 and / or GLUT4) translocation can be beneficial for treating, ameliorating, or preventing diseases or disorders such as rhabdomyosarcoma.

[0184] Also disclosed herein are methods and uses for treating a disease or disorder in a subject. In some embodiments, the methods and uses are directed to administering a protein to a subject who has, is suspected of having, or is at risk of developing a disease or disorder. In some embodiments, the protein is an anti-Gal3 antibody or a binding fragment thereof. In some embodiments, the disease or disorder is insulin resistance, a disease or disorder associated with insulin resistance, or a disease or disorder that includes symptoms of insulin resistance. In some embodiments, the method comprises administering any antibody or variant thereof as provided herein (including any having one or more of the six CDRs provided in this disclosure) in a therapeutically effective amount sufficient to interfere with the interaction between GAL3 and GLUT (e.g., GLUT1 and / or GLUT4) to treat (depending on the subject having and / or reducing the risk of) one or more of diabetes mellitus, insulin resistance, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer.

[0185] In some embodiments, there is a method of improving insulin sensitivity in a subject in need thereof. The method comprises administering to the subject an anti-Gal3 antibody or binding fragment thereof. In some embodiments, binding of the anti-Gal3 antibody or binding fragment thereof to Gal3 in the subject inhibits blockage of Gal3-mediated GLUT translocation in the subject, thereby improving insulin sensitivity in the subject. In some embodiments, the GLUT is GLUT1 and / or GLUT4. In some embodiments, the method further comprises identifying a subject in need of improved insulin sensitivity prior to the administering step. In some embodiments, the method further comprises detecting improved insulin sensitivity in the subject after the administering step. In some embodiments, detecting improved insulin sensitivity in the subject is performed by measuring blood glucose levels, measuring blood insulin levels, a glucose tolerance test, or a hyperinsulinemic-euglycemic clamp. In some embodiments, the insulin sensitivity in the subject is improved by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or any percentage within a range defined by any two of the foregoing percentages, compared to the insulin sensitivity of the subject before the administering step. In some embodiments, the anti-Gal3 antibody or binding fragment thereof selectively binds to the N-terminal domain of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to peptide 1 (SEQ ID NO: 3), peptide 6 (SEQ ID NO: 8), or peptide 7 (SEQ ID NO: 9), or any combination thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to (1) V H -CDR1, V H -CDR2, and V H a heavy chain variable region comprising CDR3; and (2) V L -CDR1, V L -CDR2, and V L In some embodiments, the V H- CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 27-70. H -CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 71-111, 801, 951, and 952. In some embodiments, the V H -CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 112-169, 802, 953, and 954. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220. L - CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 221-247. L- CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 248-296. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, and V L -CDR3 In some embodiments, the heavy chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, and 1415-1439. In some embodiments, the light chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 374-447, 821-835, 969-982, 1110-1152, and 1440-1464. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, and 1490-1514. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19 D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F84 6C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F1 0, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849 C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846 .2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B 11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 84 7.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847 .4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D 10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、20H5.A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v2-QDT、2D10-hVH1-h. VL1、2D10-hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-hVL4、2D10-hV H2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL4、20H5 .A3-hIgG4(S228P)、20H5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0mL1、798-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1mL1、798-9.20 H5.A3-mH2mL0, 798-9.20H5.A3-mH2mL1, 20H5.A3-VH1VL1, 20H5.A3-VH1VL2, 20H5.A3-VH1VL3, 20H5.A3-VH1VL4, 20H5.A3-VH1VL5, 20H5 A3-VH1VL6、20H5.A3-VH2VL3、20H5.A3-VH2VL4、20H5.A3-VH2VL5、20H5.A3-VH2VL6、20H5.A3-VH3VL5、20H5.A3-VH3VL6、20H5.A3-VH4VL 3、20H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3-VH5VL5、20H5.A3-VH5VL6、20H5.A3-VH6VL4、20H5.A3-VH6VL5、20H5.A 3-VH6VL6、20H5.A3-VH7VL1、20H5.A3-VH7VL2、20H5.A3-VH7VL3、20H5.A3-VH7VL4、20H5.A3-VH7VL5、20H5.A3-VH7VL6、20H5.A3_hVH3VL1 -hIgG1(KEMv2)、20H5.A3_hVH3VL1-hIgG1(LALAPGv2)、20H5.A3_hVH3VL1-hIgG1(REM)、20H5.A3_hVH5VL1-hIgG1(KEMv2)、20H5.A3_hVH5VL1-hIgG1(LALAPGv2)、20H5.A3_hVH5VL1-hIgG1(REM)、20H5.A3_hVH6VL1-hIgG1(KEMv2)、20H5.A3_hVH6VL1-hIgG1(LALAPGv2)、20H5.A3_hVH6VL1-hIgG1(REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21 H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3 L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 20H5.A3, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, and selected from the group consisting of 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0186] In some embodiments, a method for improving insulin sensitivity in a subject in need thereof is provided. The method includes improving insulin sensitivity in a subject by administering to the subject a preincubated complex of Gal3 with an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the preincubated complex of Gal3 with the anti-Gal3 antibody or binding fragment thereof is formed by a mass ratio of Gal3 and the anti-Gal3 antibody or binding fragment thereof of 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, or 1:2.5, or any mass ratio within a range defined by any two of the above mass ratios. In some embodiments, the pre-incubation of Gal3 with the anti-Gal3 antibody or binding fragment thereof to form a complex comprises Gal3 at, or about, a concentration of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 μg / mL, or any concentration within a range defined by any two of the above concentrations. 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 , 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 μg / mL, or at about that concentration, or any concentration within a range defined by any two of the above concentrations.In some embodiments, the GLUT is GLUT1 and / or GLUT4. In some embodiments, the method further comprises identifying a subject in need of improved insulin sensitivity prior to the administering step. In some embodiments, the method further comprises detecting improved insulin sensitivity in the subject after the administering step. In some embodiments, detecting improved insulin sensitivity in the subject is performed by measuring blood glucose levels, measuring blood insulin levels, a glucose tolerance test, or a hyperinsulinemic-euglycemic clamp. In some embodiments, the insulin sensitivity in the subject is improved by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or any percentage within a range defined by any two of the foregoing percentages, compared to the insulin sensitivity of the subject before the administering step. In some embodiments, the anti-Gal3 antibody or binding fragment thereof selectively binds to the N-terminal domain of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to peptide 1 (SEQ ID NO: 3), peptide 6 (SEQ ID NO: 8), or peptide 7 (SEQ ID NO: 9), or any combination thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to (1)V. H -CDR1, V H -CDR2, and V H a heavy chain variable region comprising CDR3; and (2) V L -CDR1, V L -CDR2, and V L - a light chain variable region comprising CDR3. In some embodiments, the V H- CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 27-70. H -CDR2 is any one of the amino acid sequences of SEQ ID NOs: 71 to 111, 801, 951, and 952, In some embodiments, the V comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the V. H -CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 112-169, 802, 953, and 954. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220. L - CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 221-247. L- CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 248-296. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, and V LIn some embodiments, the heavy chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, and 1415-1439. In some embodiments, the light chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 374-447, 821-835, 969-982, 1110-1152, and 1440-1464. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, and 1490-1514. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2 , 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, F84 6C.1B2、F846C.1F5、F846C.1H12、F846C.1H5、F846C.2H3、F846TC.14A2、F8 46TC.14E4、F846TC.16B5、F846TC.7F10、F847C.10B9、F847C.11B1、F847C. 12F12、F847C.26F5、F847C.4B10、F849C.8D10、F849C.8H3、846.2B11、846. 4D5、846T.1H2、847.14H4、846.2D4、846.2F11、846T.10B1、846T.2E3、846T .4C9、846T.4E11、846T.4F5、846T.8D1、847.10C9、847.11D6、847.15D12、8 47.15F9、847.15H11、847.20H7、847.21B11、847.27B9、847.28D1、847.2B8 、847.3B3、849.1D2、849.2D7、849.2F12、849.4B2、849.4F12、849.4F2、849 .5C2、849.8D12、F847C.21H6、849.5H1、847.23F11、847.16D10、847.13E2-m H0mL1、847.13E2-mH0mL2、847.12C4、847.4D3、2D10-VH0-VL0、2D10-hVH4- HVL1、2D10-hVH4-HVL2、2D10-hVH4-HVL3、2D10-hVH4-HVL4、2D10-hVH3-HV L1、2D10-hVH3-HVL2、2D10-hVH3-HVL3、2D10-hVH3-HVL4、20H5.A3-VH3VL1、20H5.A3-VH3VL3、20H5.A3-VH4VL1、20H5.A3-VH5VL1、20H5.A3-VH5VL3、2 0H5.A3-VH6VL1、20H5.A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v2-QDT、 2D10-hVH1-hVL1、2D10-hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-hVL4、2D 10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL4、20H5.A3-hIgG4(S228P)、20H5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0mL1、798-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1mL1、798-9.20H5.A3-mH2mL0、798-9.20H5.A3-mH2mL1、20H5.A3-VH1VL1、20H5.A3-VH1VL2、20H5.A3-VH1VL3、20H5.A3 -VH1VL4、20H5.A3-VH1VL5、20H5.A3-VH1VL6、20H5.A3-VH2VL3、20H5.A3-VH2VL4、20H5.A3-VH2VL5、20H5.A3-VH2VL6、20H5.A3-VH3VL5、20H5.A3-VH3VL6、20H5.A3-VH4VL3、20H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3-VH 5VL5, 20H5.A3-VH5VL6, 20H5.A3-VH6VL4, 20H5.A3-VH6VL5, 20H5.A3-VH6VL6, 20H5.A3-VH7VL1, 20H5.A3-VH7VL2, 20H5.A3-VH7VL3, 20H5.A3-VH7VL4, 20H5.A3-VH7VL5, 20H5.A3-VH7VL6, 20H5.A3_hVH3VL1-hIgG1(KEMv2), 20H5.A3_hVH3VL 1-hIgG1(LALAPGv2)、20H5.A3_hVH3VL1-hIgG1(REM)、20H5.A3_hVH5VL1-hIgG1(KEMv2)、20H5.A3_hVH5VL1-hIgG1(LALAPGv2)、20H5.A3_hVH5VL1-hIgG1(REM)、20H5.A3_hVH6VL1-hIgG1(KEMv2)、20H5.A3_hVH6VL1-hIgG1(LALAPGv2)、20H5.A3_hVH6VL1-hIgG1(REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6- H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 2. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 1H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 20H5.A3, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0187] In some embodiments, there are methods for treating a disease associated with insulin resistance in a subject in need thereof. In some embodiments, the method comprises treating the disease associated with insulin resistance in the subject by administering an anti-Gal3 antibody or binding fragment thereof to the subject. In some embodiments, the disease associated with insulin resistance comprises diabetes mellitus, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer. In some embodiments, the method further comprises identifying a subject in need of treatment for the disease associated with insulin resistance prior to the administering step. In some embodiments, the method further comprises detecting an improvement in the disease associated with insulin resistance after the administering step. In some embodiments, detecting an improvement in the disease associated with insulin resistance comprises detecting an improvement in insulin sensitivity in the subject. In some embodiments, detecting improved insulin sensitivity in the subject is performed by measuring blood glucose levels, measuring blood insulin levels, a glucose tolerance test, or a hyperinsulinemic-euglycemic clamp. In some embodiments, the insulin sensitivity in the subject is improved by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or any percentage within a range defined by any two of the foregoing percentages, compared to the subject's insulin sensitivity before the administering step. In some embodiments, the anti-Gal3 antibody or binding fragment thereof selectively binds to the N-terminal domain of Gal3. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to peptide 1 (SEQ ID NO:3), peptide 6 (SEQ ID NO:8), or peptide 7 (SEQ ID NO:9), or any combination thereof.In some embodiments, the anti-Gal3 antibody or binding fragment thereof is (1)V. H -CDR1, V H -CDR2, and V H a heavy chain variable region comprising CDR3; and (2) V L -CDR1, V L -CDR2, and V L In some embodiments, the V H -CDR1 is the amino acid sequence of SEQ ID NO: 27 to 70 In some embodiments, the V comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the V H -CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 71-111, 801, 951, and 952. In some embodiments, the V H -CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 112-169, 802, 953, and 954. In some embodiments, the V L - CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220. L- CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 221-247. L - CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 248-296. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a V H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, and V LIn some embodiments, the heavy chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, and 1415-1439. In some embodiments, the light chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, and 1440-1464. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, and 1490-1514. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F 10.2D6、19B5.2E6、20D11.2C6、20H5.A3、23H9.2E4、2D10.2B2、3B11.2G2、7D8.2D8、mIMT001、4A11.2B5、4A11.H1L1、4A11.H4L2、4G2.2G6、6B3.2D3、 6H6.2D6、9H2.2H10、13G4.2F8、13H12.2F8、15G7.2A7、19D9.2E5、23B10.2 B12、24D12.2H9、F846C.1B2、F846C.1F5、F846C.1H12、F846C.1H5、F846C. 2H3、F846TC.14A2、F846TC.14E4、F846TC.16B5、F846TC.7F10、F847C.10B 9、F847C.11B1、F847C.12F12、F847C.26F5、F847C.4B10、F849C.8D10、F84 9C.8H3、846.2B11、846.4D5、846T.1H2、847.14H4、846.2D4、846.2F11、84 6T.10B1、846T.2E3、846T.4C9、846T.4E11、846T.4F5、846T.8D1、847.10C9 、847.11D6、847.15D12、847.15F9、847.15H11、847.20H7、847.21B11、847 .27B9、847.28D1、847.2B8、847.3B3、849.1D2、849.2D7、849.2F12、849.4 B2、849.4F12、849.4F2、849.5C2、849.8D12、F847C.21H6、849.5H1、847.23F11、847.16D10、847.13E2-mH0mL1、847.13E2-mH0mL2、847.12C4、847.4D 3、2D10-VH0-VL0、2D10-hVH4-HVL1、2D10-hVH4-HVL2、2D10-hVH4-HVL3、2D10-hVH4-HVL4、2D10-hVH3-HVL1、2D10-hVH3-HVL2、2D10-hVH3-HVL3、2D 10-hVH3-HVL4、20H5.A3-VH3VL1、20H5.A3-VH3VL3、20H5.A3-VH4VL1、20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、20H5.A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v2-QDT、2D10-hVH1-hVL1、2D10-hVH1-hVL2、2D 10-hVH1-hVL3、2D10-hVH1-hVL4、2D10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL4、20H5.A3-hIgG4(S228P)、20H5.A3-hIgG4 (S228P)-mv2、798-9.20H5.A3-mH0mL1、798-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1mL1、798-9.20H5.A3-mH2mL0、798-9.20H5.A3-mH2mL1、20H5. A3-VH1VL1、20H5.A3-VH1VL2、20H5.A3-VH1VL3、20H5.A3-VH1VL4、20H5.A3-VH1VL5、20H5.A3-VH1VL6、20H5.A3-VH2VL3、20H5.A3-VH2VL4、20H5.A3 -VH2VL5、20H5.A3-VH2VL6、20H5.A3-VH3VL5、20H5.A3-VH3VL6、20H5.A3-VH4VL3、20H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3-V H5VL5、20H5.A3-VH5VL6、20H5.A3-VH6VL4、20H5.A3-VH6VL5、20H5.A3-VH6VL6、20H5.A3-VH7VL1、20H5.A3-VH7VL2、20H5.A3-VH7VL3、20H5.A3-VH7 VL4、20H5.A3-VH7VL5、20H5.A3-VH7VL6、20H5.A3_hVH3VL1-hIgG1(KEMv2)、20H5.A3_hVH3VL1-hIgG1(LALAPGv2)、20H5.A3_hVH3VL1-hIgG1(REM)、 20H5.A3_hVH5VL1-hIgG1(KEMv2)、20H5.A3_hVH5VL1-hIgG1(LALAPGv2)、20H5.A3_hVH5VL1-hIgG1(REM)、20H5.A3_hVH6VL1-hIgG1(KEMv2)、20H5.A3_hVH6VL1-hIgG1(LALAPGv2), 20H5.A3_hVH6VL1-hI. gG1(REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21 H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6 -H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 20H5.A3, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0188] In some embodiments, there is a method of treating a disease associated with insulin resistance in a subject in need thereof, comprising administering to the subject a complex preincubated with Gal3 and an anti-Gal3 antibody or binding fragment thereof, thereby treating the disease associated with insulin resistance in the subject. In some embodiments, the pre-incubation of Gal3 with the anti-Gal3 antibody or binding fragment thereof to form a complex is made of Gal3 and the anti-Gal3 antibody or binding fragment thereof at a mass ratio of 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, or 1:2.5, or approximately such a mass ratio, or any mass ratio within a range defined by any two of the above mass ratios. In some embodiments, the pre-incubation complex of Gal3 with the anti-Gal3 antibody or binding fragment thereof is at a concentration of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 μg / mL; Gal3 at or about that concentration, or any concentration within a range defined by any two of the above concentrations, and The anti-Gal3 antibody or binding fragment thereof is produced at a concentration of, or about, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 μg / mL, or at any concentration within a range defined by any two of the above concentrations. In some embodiments, the disease associated with insulin resistance comprises diabetes mellitus, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer. In some embodiments, the method further comprises identifying a subject in need of treatment for the disease associated with insulin resistance prior to the administering step. In some embodiments, the method further comprises detecting an improvement in the disease associated with insulin resistance after the administering step. In some embodiments, detecting an improvement in the disorder associated with insulin resistance comprises detecting an improvement in insulin sensitivity in the subject. In some embodiments, detecting an improvement in insulin sensitivity in the subject is performed by measuring blood glucose levels, measuring blood insulin levels, a glucose tolerance test, or a hyperinsulinemic-euglycemic clamp. In some embodiments, the insulin sensitivity in the subject is improved by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200%, or any percentage within a range defined by any two of the above percentages, compared to the subject's insulin sensitivity before the administering step. In some embodiments, the anti-Gal3 antibody or binding fragment thereof selectively binds to the N-terminal domain of Gal3.In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to peptide 1 (SEQ ID NO: 3), peptide 6 (SEQ ID NO: 8), or peptide 7 (SEQ ID NO: 9), or any combination thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to (1)V. H -CDR1, V H -CDR2, and V H a heavy chain variable region comprising CDR3; and (2) V L -CDR1, V L -CDR2, and V L In some embodiments, the V H - CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 27-70. H -CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 71-111, 801, 951, and 952. In some embodiments, the V H -CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 112-169, 802, 953, and 954. In some embodiments, the V L- CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220. L - CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the amino acid sequences of SEQ ID NOs: 221-247. L -CDR3 is an amino acid sequence of SEQ ID NOs: 248 to 296 In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of the VV ... H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, and V LIn some embodiments, the heavy chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, and 1415-1439. In some embodiments, the light chain variable region comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, and 1440-1464. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, and 1490-1514. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13 H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846T C.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B1 1, 846.4D5, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.1 1D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849. 4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12 C4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2 D10-hVH3-HVL3、2D10-hVH3-HVL4、20H5.A3-VH3VL1、20H5.A3-VH3VL3、20H5.A3-VH4VL1、20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、20H5. A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v2-QDT、2D10-hVH1-hVL1、2D10- hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-hVL4、2D10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL4、20H5.A3-hIgG4(S228P)、20H5 .A3-hIgG4(S228P)-mv2、798-9.20H5.A3-mH0mL1、798-9.20H5.A3-mH1mL0、798-9.20H5.A3-mH1mL1、798-9.20H5.A3-mH2mL0、798-9.20H5.A3-mH2mL1 20H5.A3-VH1VL1、20H5.A3-VH1VL2、20H5.A3-VH1VL3、20H5.A3-VH1VL4、20H5.A3-VH1VL5、20H5.A3-VH1VL6、20H5.A3-VH2VL3、20H5.A3-VH2VL4、20H 5.A3-VH2VL5、20H5.A3-VH2VL6、20H5.A3-VH3VL5、20H5.A3-VH3VL6、20H5.A3-VH4VL3、20H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3- VH5VL5、20H5.A3-VH5VL6、20H5.A3-VH6VL4、20H5.A3-VH6VL5、20H5.A3-VH6VL6、20H5.A3-VH7VL1、20H5.A3-VH7VL2、20H5.A3-VH7VL3、20H5.A3-VH7VL 4、20H5.A3-VH7VL5、20H5.A3-VH7VL6、20H5.A3_hVH3VL1-hIgG1(KEMv2)、20H5.A3_hVH3VL1-hIgG1(LALAPGv2)、20H5.A3_hVH3VL1-hIgG1(REM)、20H5.A3_hVH5VL1-hIgG1(KEMv2), 20H5.A3_hVH5VL1-hIgG1(LALAPGv2), 20H5.A3_hVH5VL1-hIgG1(REM), 20H5.A3_hVH6VL1-hIgG1(KEMv2), 20H5.A3_hVH6VL1-hIgG1(LALAPGv2), 20H5.A3_hVH6VL1-hIgG1(REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is 20H5.A3, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H. 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

[0189] In some embodiments, there are methods for diagnosing a disease or disorder, or a symptom thereof, in a subject. In some embodiments, the disease or disorder is associated with insulin resistance. In some embodiments, the disease or disorder is diabetes mellitus, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes mellitus (PCDM), or cancer. In some embodiments, the disease or disorder is diabetes mellitus. In some embodiments, the disease or disorder is insulin-dependent diabetes mellitus. In some embodiments, the disease or disorder is non-insulin-dependent diabetes mellitus. In some embodiments, the disease or disorder is type I diabetes. In some embodiments, the disease or disorder is type II diabetes. In some embodiments, the method comprises contacting a subject, or a portion of a subject (e.g., tissue, blood / serum), with an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is conjugated to a detectable moiety. In some embodiments, any of the methods disclosed herein involving an anti-Gal3 antibody or binding fragment can be performed with an antigen-binding molecule that binds to Gal3.

[0190] As applied to any of the methods of use disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to one or more of the peptides set forth in SEQ ID NOs: 3-26. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to an epitope present within a region of Gal3 defined by peptide 1 (ADNFSLHDALSGSGNPNPQG; SEQ ID NO: 3), peptide 4 (GAGGYPGASYPGAYPGQAPP; SEQ ID NO: 6), peptide 6 (GAYPGQAPPGAYPGAPGAYP; SEQ ID NO: 8), peptide 7 (AYPGAPGAYPGAPAPGVYPG; SEQ ID NO: 9), or a combination thereof. In some embodiments, any of the methods disclosed herein involving an anti-Gal3 antibody or binding fragment may be practiced with an antigen-binding molecule that binds to Gal3.

[0191] As applied to any of the methods of use disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to an epitope of Gal3 containing a GxYPG motif, where x is the amino acid alanine (A), glycine (G), or valine (V). In some embodiments, the anti-Gal3 antibody as described herein binds to an epitope of Gal3 containing two GxYPG motifs separated by three amino acids, where x is A, G, or V. In some embodiments, any of the methods disclosed herein involving an anti-Gal3 antibody or binding fragment may be performed with an antigen-binding molecule that binds to Gal3.

[0192] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: (1) V L -CDR1, V L -CDR2, and V L a light chain variable region comprising CDR3; and (2) V H -CDR1, V H -CDR2, and V H In some embodiments, the V L- CDR1 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to any of the amino acid sequences of SEQ ID NOs: 170 to 220. In some embodiments, the V L -CDR2 has a sequence similar to that of any one of the amino acid sequences of SEQ ID NOs: 221 to 247, and is at least 60%, at least 70%, at least 80%, at least 90%, or In some embodiments, the V L - CDR3 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to the amino acid sequence of any of SEQ ID NOs: 248 to 296. In some embodiments, the V H - CDR1 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to the amino acid sequence of any of SEQ ID NOs: 27 to 70. In some embodiments, the V H -CDR2 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to any of the amino acid sequences of SEQ ID NOs: 71-111, 801, 951, and 952. In some embodiments, the V H - CDR3 comprises an amino acid sequence having at least 60%, at least 70%, at least 80%, at least 90%, or 100% sequence identity to the amino acid sequence of any of SEQ ID NOs: 112-169, 802, 953, and 954. In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed with an antigen-binding molecule that binds to Gal3.

[0193] As applied to any of the uses disclosed herein, in some embodiments, the exemplary V H -CDR1 sequences are shown in Figure 19A. In some embodiments, exemplary V H-CDR2 sequences are shown in Figure 19B. In some embodiments, exemplary V H -CDR3 sequences are shown in Figure 19C. In some embodiments, exemplary V L -CDR1 sequences are shown in Figure 20A. In some embodiments, exemplary V L -CDR2 sequences are shown in Figure 20B. In some embodiments, exemplary V L - The CDR3 sequence is shown in Figure 20C.

[0194] As applied to any of the methods of use disclosed herein, in some embodiments, the heavy chain variable region of any of the anti-Gal3 antibodies or binding fragments thereof disclosed herein comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95%, or 100% sequence identity to any of the sequences set forth in SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, and 1415-1439. In some embodiments, the heavy chain variable region of any of the anti-Gal3 antibodies or binding fragments thereof disclosed herein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, and 1415-1439. In some embodiments, exemplary V H is shown in Figure 21. In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be practiced with antigen-binding molecules that bind to Gal3.

[0195] As applied to any of the methods of use disclosed herein, in some embodiments, the light chain variable region of any of the anti-Gal3 antibodies or binding fragments thereof disclosed herein comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95%, or 100% sequence identity to any of the sequences set forth in SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, and 1440-1464. In some embodiments, the light chain variable region of any of the anti-Gal3 antibodies or binding fragments thereof disclosed herein comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, and 1440-1464. In some embodiments, exemplary V L is shown in Figure 22. In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be practiced with antigen-binding molecules that bind to Gal3.

[0196] As applied to any of the uses disclosed herein, some embodiments In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain sequence of any one of SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, and 1465-1489. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain sequence of any one of SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, and 1490-1514.

[0197] As applied to any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, F846 C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846 TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12 F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5 , 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C 9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.1 5F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847 .3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL 1, 847.13E2-mH0mL2, 847.12C4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D 10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3、20H5.A3-VH4VL1、20H5.A3-VH5VL1、20H5.A3-VH5VL3、20H5.A3-VH6VL1、20H5.A3-VH6VL3、2D10.2B2-v2、2D10-VH0-NDA-VL0、2D10-VH0-QDT-VL0、2D10-VH0-SDT-VL0、2D10-VH0-v1-QDT、2D10-VH0-v2-QDT、 2D10-hVH1-hVL1、2D10-hVH1-hVL2、2D10-hVH1-hVL3、2D10-hVH1-hVL4、2D10-hVH2-hVL1、2D10-hVH2-hVL2、2D10-hVH2-hVL3、2D10-hVH2-hVL4、20H5.A3-hIgG4(S228P)、20H5.A3-hIgG4(S228P)-mv2、798-9.20H5.A3- mH0mL1, 798-9.20H5.A3-mH1mL0, 798-9.20H5.A3-mH1mL1, 798-9.20H5.A3-mH2mL0, 798-9.20H5.A3-mH2mL1, 20H5.A3-VH1VL1, 20H5.A3-VH1VL2, 20H5.A3-VH1VL3, 20H5.A3-VH1VL4, 20H5.A3-VH1VL5, 20H5.A3-VH1VL6 、20H5.A3-VH2VL3、20H5.A3-VH2VL4、20H5.A3-VH2VL5、20H5.A3-VH2VL6、20H5.A3-VH3VL5、20H5.A3-VH3VL6、20H5.A3-VH4VL3、20H5.A3-VH4VL4、20H5.A3-VH4VL5、20H5.A3-VH4VL6、20H5.A3-VH5VL5、20H5.A3-VH5VL6. 20H5.A3-VH6VL4, 20H5.A3-VH6VL5, 20H5.A3-VH6VL6, 20H5.A3-VH7VL1, 20H5.A3-VH7VL2, 20H5.A3-VH7VL3, 20H5.A3-VH7VL4, 20H5.A3-VH7VL5, 20H5.A3-VH7VL6, 20H5.A3_hVH3VL1-hIgG1(KEMv2), 20H5 .A3_hVH3VL1-hIgG1(LALAPGv2)、20H5.A3_hVH3VL1-hIgG1(REM)、20H5.A3_hVH5VL1-hIgG1(KEMv2)、20H5.A3_hVH5VL1-hIgG1(LALAPGv2)、20H5.A3_hVH5VL1-hIgG1(REM)、20H5.A3_hVH6VL1-hIgG1(KEMv 2)、20H5.A3_hVH6VL1-hIgG1(LALAPGv2)、20H5.A3_hVH6VL1-hIgG1(REM)、21H6-H0L0、21H6-H1L1、21H6-H1L2、21H6-H1L3、21H6-H1L4、21H6-H2L1、21H6-H2L2、21H6-H2L3、21H6-H2L4、21H6-H3L1、21H6-H3 L2、21H6-H3L3、21H6-H3L4、21H6-H4L1、21H6-H4L2、21H6-H4L3、21H6-H4L4、21H6-H5L1、21H6-H5L2、21 H6-H5L3、21H6-H5L4、21H6-H6L1、21H6-H6L2、21H6 -H6L3, 21H6-H6L4,

[0198] As applied to any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibodies or binding fragments thereof exclude the subset of named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 38A-38D. In some embodiments, CDRs (including heavy and light chain CDRs), heavy chain variable regions, light chain variable regions, heavy chains, and / or light chains are excluded from the sequences associated with the subset of named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 38A-38D. In some embodiments, combinations of CDRs (including heavy and light chain CDRs), combinations of heavy chain variable regions, combinations of light chain variable regions, combinations of heavy chains, and / or combinations of light chains are excluded from the sequences associated with the subset of named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 38A-38D, or exclude any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38A, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38B, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38C, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC.In some embodiments, the anti-Gal3 antibody or binding fragment thereof excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38D, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks the interaction between Gal3 and GLUT (e.g., GLUT1 and / or GLUT4) and excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38A, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks the interaction between Gal3 and GLUT (e.g., GLUT1 and / or GLUT4). In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks the interaction between Gal3 and a GLUT (e.g., GLUT1 and / or GLUT4) and excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38B, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks the interaction between Gal3 and a GLUT (e.g., GLUT1 and / or GLUT4) and excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38C, or excludes any one or more of their CDRs, VH, VL, HC, and / or LC. In some embodiments, the anti-Gal3 antibody or binding fragment thereof blocks the interaction between Gal3 and GLUT (e.g., GLUT1 and / or GLUT4) and excludes one selected from the group of named anti-Gal3 antibodies or binding fragments thereof shown in Figure 38D, or excludes any one or more of its CDRs, VH, VL, HC, and / or LC. In other embodiments, any of these constructs (e.g., those in Figures 38A-38D) are used in any of the methods provided herein.

[0199] As applied to any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the subset of named anti-Gal3 antibodies or binding fragments thereof shown in any one of Figures 39A-39...

Claims

**Claim 1**: (1) A heavy chain variable region (VH) comprising VH - CDR1, VH - CDR2, and VH - CDR3; and (2) A light chain variable region (VL) comprising VL - CDR1, VL - CDR2, and VL - CDR3, an anti - Gal3 antibody or a binding fragment thereof, wherein said VH - CDR1 comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NO: 32, 37, and 66; said VH - CDR2 comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NO: 77 - 78, 108, and 801; said VH - CDR3 comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NO: 118, 120, 164, and 802; said VL - CDR1 comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NO: 171, 178, and 215; said VL - CDR2 comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NO: 222, 225, and 229; said VL - CDR3 comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NO: 256 - 257, and 291, an anti - Gal3 antibody or a binding fragment thereof. **Claim 2**: The anti - Gal3 antibody or a binding fragment thereof according to claim 1, wherein said VH comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NO: 305 - 306, 367, 806 - 820, 1067 - 1109, and 1415 - 1439, and said VL comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NO: 382 - 383, 440, 821 - 835, 1110 - 1152, and 1440 - 1464. **Claim 3**: The VH is encoded by a nucleic acid sequence having at least 80% identity to any one of the nucleic acid sequences of SEQ ID NOs: 547, 613, 797, 866-880, 1239-1281, and 1515-1539, and the VL is encoded by a nucleic acid sequence having at least 80% identity to any one of the nucleic acid sequences of SEQ ID NOs: 629, 695, 798, 881-895, 1282-1324, and 1540-1564, the anti-Gal3 antibody according to claim 1 or a binding fragment thereof. **Claim 4**: An anti-Gal3 antibody or a binding fragment thereof comprising (1) a heavy chain variable region (VH); and (2) a light chain variable region (VL), wherein the VH region comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NOs: 305-306, 367, 806-820, 1067-1109, and 1415-1439, and the VL comprises an amino acid sequence having at least 80% identity to any one of the amino acid sequences of SEQ ID NOs: 382-383, 440, 821-835, 1110-1152, and 1440-1464, the anti-Gal3 antibody or a binding fragment thereof. **Claim 5**: An anti-Gal3 antibody or a binding fragment thereof comprising (1) a heavy chain variable region (VH); and (2) a light chain variable region (VL), wherein the VH is encoded by a nucleic acid sequence having at least 80% identity to any one of the nucleic acid sequences of SEQ ID NOs: 547, 613, 797, 866-880, 1239-1281, and 1515-1539, and the VL is encoded by a nucleic acid sequence having at least 80% identity to any one of the nucleic acid sequences of SEQ ID NOs: 629, 695, 798, 881-895, 1282-1324, and 1540-1564, the anti-Gal3 antibody or a binding fragment thereof. **Claim 6**: (1) A heavy chain variable region (VH) comprising VH - CDR1, VH - CDR2, and VH - CDR3; and (2) A light chain variable region (VL) comprising VL - CDR1, VL - CDR2, and VL - CDR3, an anti - Gal3 antibody or a binding fragment thereof, wherein said VH - CDR1 comprises the amino acid sequence of SEQ ID NO: 37, said VH - CDR2 comprises the amino acid sequence of SEQ ID NO: 77, said VH - CDR3 comprises the amino acid sequence of SEQ ID NO: 118, said VL - CDR1 comprises the amino acid sequence of SEQ ID NO: 178, said VL - CDR2 comprises the amino acid sequence of SEQ ID NO: 229, said VL - CDR3 comprises the amino acid sequence of SEQ ID NO: 256, or, said VH - CDR1 comprises the amino acid sequence of SEQ ID NO: 32, said VH - CDR2 comprises the amino acid sequence of SEQ ID NO: 78, said VH - CDR3 comprises the amino acid sequence of SEQ ID NO: 120, said VL - CDR1 comprises the amino acid sequence of SEQ ID NO: 171, said VL - CDR2 comprises the amino acid sequence of SEQ ID NO: 222, said VL - CDR3 comprises the amino acid sequence of SEQ ID NO: 257, or, said VH - CDR1 comprises the amino acid sequence of SEQ ID NO: 32, said VH - CDR2 comprises the amino acid sequence of SEQ ID NO: 801, said VH - CDR3 comprises the amino acid sequence of SEQ ID NO: 802, said VL - CDR1 comprises the amino acid sequence of SEQ ID NO: 171, said VL - CDR2 comprises the amino acid sequence of SEQ ID NO: 222, said VL - CDR3 comprises the amino acid sequence of SEQ ID NO: 257, or, said VH - CDR1 comprises the amino acid sequence of SEQ ID NO: 66, said VH - CDR2 comprises the amino acid sequence of SEQ ID NO: 108, said VH - CDR3 comprises the amino acid sequence of SEQ ID NO: 164, said VL - CDR1 comprises the amino acid sequence of SEQ ID NO: 215, said VL - CDR2 comprises the amino acid sequence of SEQ ID NO: 225, said VL - CDR3 comprises the amino acid sequence of SEQ ID NO: 291, including, an anti - Gal3 antibody or a binding fragment thereof. **Claim 7**: The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 305, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 382, or the VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 306, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 383, or the VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 367, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 340, or the VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 806, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 821, or the VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 807, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 822, or the VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 808, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 823, or the VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 809, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 824, or the VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 810, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 825, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 811, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 826, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 812, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 827, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 813, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 828, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 814, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 829, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 815, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 830, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 816, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 831, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 817, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 832, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 818, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 833, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 819, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 834, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 820, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 815, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1067, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1110, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1068, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1111, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1069, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1112, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1070, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1113, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1071, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1114, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1072, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1115, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1073, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1116, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1074, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1117, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1075, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1118, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1076, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1119, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1077, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1120, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1078, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1121, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1079, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1122, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1080, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1123, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1081, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1124, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1082, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1125, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1083, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1126 and comprises an amino acid sequence, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1084, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1127, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1085, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1128, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1086, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1129, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1087, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1130, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1088, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1131, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1089, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1132, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1090, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1133, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1091, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1134, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1092, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1135, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1093, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1136, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1094, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1137, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1095, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1138, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1096, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1139, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1097, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1140, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1098, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1141, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1099, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1142, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1100, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1143, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1101, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1144, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1102, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1145, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1103, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1146, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1104, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1147, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1105, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1148, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1106, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1149, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1107, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1150, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1108, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1151, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1109, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1152, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1415, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1440, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1416, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1441, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1417, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1442, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1418, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1443, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1419, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1444, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1420, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1445, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1421, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1446, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1422, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1447, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1423, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1448, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1424, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1449, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1425, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1450, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1426, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1451, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1427, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1452, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1428, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1453, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1429, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1454, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1430, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1455, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1431, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1456, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1432, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1457, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1433, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1458, or The VH contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1434, and the VL contains an amino acid sequence having at least 80% identity to SEQ ID NO: 1459, or The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1435, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1460, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1436, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1461, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1437, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1462, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1438, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1463, and comprises an amino acid sequence, or, The VH comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1439, and the VL comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 1464, The anti-Gal3 antibody or a binding fragment thereof according to claim 6.

8. The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 547, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 629, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 613, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 695, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 797, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 798, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 866, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 881, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 867, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 882, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 868, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 883, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 869, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 884, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 870, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 885, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 871, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 886, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 872, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 887, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 873, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 888, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 874, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 889, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 875, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 890, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 876, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 891, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 877, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 892, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 878, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 893, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 879, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 894, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 880, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 895, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1011, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1025, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1012, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1026, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1013, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1027, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1014, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1028, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1015, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1029, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1016, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1030, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1017, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1031, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1018, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1032, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1019, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1033, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1020, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1034, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1021, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1035, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1022, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1036, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1023, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1037, or said VH is a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1024 and is encoded thereby, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1038, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1239, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1282, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1240, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1283, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1241, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1284, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1242, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1285, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1243, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1286, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1244, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1287, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1245, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1288, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1246, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1289, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1247, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1290, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1248, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1291, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1249, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1292, or The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1250, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1293, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1251, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1294, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1252, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1295, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1253, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1296, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1254, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1297, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1255, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1298, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1256, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1299, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1257, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1300, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1258, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1301, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1259, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1302, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1260, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1303, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1261, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1304, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1262, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1305, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1263, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1306, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1264, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1307, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1265, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1308, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1266, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1309, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1267, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1310, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1268, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1311, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1269, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1312, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1270, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1313, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1271, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1314, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1272, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1315, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1273, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1316, or said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1274, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1317, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1275, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1318, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1276, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1319, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1277, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1320, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1278, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1321, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1279, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1322, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1280, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1323, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1281, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1324, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1515, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1540, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1516, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1541, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1517, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1542, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1518, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1543, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1519, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1544, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1520, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1545, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1521 and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1546, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1522, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1547, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1523, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1548, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1524, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1549, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1525, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1550, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1526, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1551, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1527, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1552, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1528, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1553, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1529, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1554, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1530, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1555, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1531, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1556, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1532, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1557, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1533, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1558, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1534, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1559, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1535, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1560, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1536, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1561, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1537, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1562, or, said VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1538, and said VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1563, or, The VH is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1539, and the VL is encoded by a nucleic acid sequence having at least 80% identity to SEQ ID NO: 1564. The anti-Gal3 antibody or binding fragment thereof according to claim 6.

9. (1) A heavy chain variable region (VH); and (2) A light chain variable region (VL), an anti-Gal3 antibody or binding fragment thereof, comprising: The VH comprises the amino acid sequence of SEQ ID NO: 305, the VL comprises the amino acid sequence of SEQ ID NO: 382, or The VH comprises the amino acid sequence of SEQ ID NO: 306, the VL comprises the amino acid sequence of SEQ ID NO: 383, or The VH comprises the amino acid sequence of SEQ ID NO: 367, the VL comprises the amino acid sequence of SEQ ID NO: 340, or The VH comprises the amino acid sequence of SEQ ID NO: 806, the VL comprises the amino acid sequence of SEQ ID NO: 821, or The VH comprises the amino acid sequence of SEQ ID NO: 807, the VL comprises the amino acid sequence of SEQ ID NO: 822, or The VH comprises the amino acid sequence of SEQ ID NO: 808, the VL comprises the amino acid sequence of SEQ ID NO: 823, or The VH comprises the amino acid sequence of SEQ ID NO: 809, the VL comprises the amino acid sequence of SEQ ID NO: 824, or The VH comprises the amino acid sequence of SEQ ID NO: 810, the VL comprises the amino acid sequence of SEQ ID NO: 825, or The VH comprises the amino acid sequence of SEQ ID NO: 811, the VL comprises the amino acid sequence of SEQ ID NO: 826, or The VH comprises the amino acid sequence of SEQ ID NO: 812, the VL comprises the amino acid sequence of SEQ ID NO: 827, or The VH contains the amino acid sequence of SEQ ID NO: 813, the VL contains the amino acid sequence of SEQ ID NO: 828, or The VH contains the amino acid sequence of SEQ ID NO: 814, the VL contains the amino acid sequence of SEQ ID NO: 829, or The VH contains the amino acid sequence of SEQ ID NO: 815, the VL contains the amino acid sequence of SEQ ID NO: 830, or The VH contains the amino acid sequence of SEQ ID NO: 816, the VL contains the amino acid sequence of SEQ ID NO: 831, or The VH contains the amino acid sequence of SEQ ID NO: 817, the VL contains the amino acid sequence of SEQ ID NO: 832, or The VH contains the amino acid sequence of SEQ ID NO: 818, the VL contains the amino acid sequence of SEQ ID NO: 833, or The VH contains the amino acid sequence of SEQ ID NO: 819, the VL contains the amino acid sequence of SEQ ID NO: 834, or The VH contains the amino acid sequence of SEQ ID NO: 820, the VL contains the amino acid sequence of SEQ ID NO: 835, or The VH contains the amino acid sequence of SEQ ID NO: 1067, the VL contains the amino acid sequence of SEQ ID NO: 1110, or The VH contains the amino acid sequence of SEQ ID NO: 1068, the VL contains the amino acid sequence of SEQ ID NO: 1111, or The VH contains the amino acid sequence of SEQ ID NO: 1069, the VL contains the amino acid sequence of SEQ ID NO: 1112, or The VH contains the amino acid sequence of SEQ ID NO: 1070, the VL contains the amino acid sequence of SEQ ID NO: 1113, or The VH contains the amino acid sequence of SEQ ID NO: 1071, the VL contains the amino acid sequence of SEQ ID NO: 1114, or The VH contains the amino acid sequence of SEQ ID NO: 1072, the VL contains the amino acid sequence of SEQ ID NO: 1115, or The VH contains the amino acid sequence of SEQ ID NO: 1073, the VL contains the amino acid sequence of SEQ ID NO: 1116, or The VH contains the amino acid sequence of SEQ ID NO: 1074, the VL contains the amino acid sequence of SEQ ID NO: 1117, or The VH contains the amino acid sequence of SEQ ID NO: 1075, the VL contains the amino acid sequence of SEQ ID NO: 1118, or The VH contains the amino acid sequence of SEQ ID NO: 1076, the VL contains the amino acid sequence of SEQ ID NO: 1119, or The VH contains the amino acid sequence of SEQ ID NO: 1077, the VL contains the amino acid sequence of SEQ ID NO: 1120, or The VH contains the amino acid sequence of SEQ ID NO: 1078, the VL contains the amino acid sequence of SEQ ID NO: 1121, or The VH contains the amino acid sequence of SEQ ID NO: 1079, the VL contains the amino acid sequence of SEQ ID NO: 1122, or The VH contains the amino acid sequence of SEQ ID NO: 1080, the VL contains the amino acid sequence of SEQ ID NO: 1123, or The VH contains the amino acid sequence of SEQ ID NO: 1081, the VL contains the amino acid sequence of SEQ ID NO: 1124, or The VH contains the amino acid sequence of SEQ ID NO: 1082, the VL contains the amino acid sequence of SEQ ID NO: 1125, or The VH contains the amino acid sequence of SEQ ID NO: 1083, the VL contains the amino acid sequence of SEQ ID NO: 1126, or The VH contains the amino acid sequence of SEQ ID NO: 1084, the VL contains the amino acid sequence of SEQ ID NO: 1127, or The VH contains the amino acid sequence of SEQ ID NO: 1085, the VL contains the amino acid sequence of SEQ ID NO: 1128, or The VH contains the amino acid sequence of SEQ ID NO: 1086, the VL contains the amino acid sequence of SEQ ID NO: 1129, or The VH contains the amino acid sequence of SEQ ID NO: 1087, the VL contains the amino acid sequence of SEQ ID NO: 1130, or The VH contains the amino acid sequence of SEQ ID NO: 1088, the VL contains the amino acid sequence of SEQ ID NO: 1131, or The VH contains the amino acid sequence of SEQ ID NO: 1089, the VL contains the amino acid sequence of SEQ ID NO: 1132, or The VH contains the amino acid sequence of SEQ ID NO: 1090, the VL contains the amino acid sequence of SEQ ID NO: 1133, or The VH contains the amino acid sequence of SEQ ID NO: 1091, the VL contains the amino acid sequence of SEQ ID NO: 1134, or The VH contains the amino acid sequence of SEQ ID NO: 1092, the VL contains the amino acid sequence of SEQ ID NO: 1135, or The VH contains the amino acid sequence of SEQ ID NO: 1093, the VL contains the amino acid sequence of SEQ ID NO: 1136, or The VH contains the amino acid sequence of SEQ ID NO: 1094, the VL contains the amino acid sequence of SEQ ID NO: 1137, or The VH contains the amino acid sequence of SEQ ID NO: 1095, the VL contains the amino acid sequence of SEQ ID NO: 1138, or The VH contains the amino acid sequence of SEQ ID NO: 1096, the VL contains the amino acid sequence of SEQ ID NO: 1139, or The VH contains the amino acid sequence of SEQ ID NO: 1097, the VL contains the amino acid sequence of SEQ ID NO: 1140, or The VH contains the amino acid sequence of SEQ ID NO: 1098, the VL contains the amino acid sequence of SEQ ID NO: 1141, or The VH contains the amino acid sequence of SEQ ID NO: 1099, and the VL contains the amino acid sequence of SEQ ID NO: 1142, or The VH contains the amino acid sequence of SEQ ID NO: 1100, and the VL contains the amino acid sequence of SEQ ID NO: 1143, or The VH contains the amino acid sequence of SEQ ID NO: 1101, and the VL contains the amino acid sequence of SEQ ID NO: 1144, or The VH contains the amino acid sequence of SEQ ID NO: 1102, and the VL contains the amino acid sequence of SEQ ID NO: 1145, or The VH contains the amino acid sequence of SEQ ID NO: 1103, and the VL contains the amino acid sequence of SEQ ID NO: 1146, or The VH contains the amino acid sequence of SEQ ID NO: 1104, and the VL contains the amino acid sequence of SEQ ID NO: 1147, or The VH contains the amino acid sequence of SEQ ID NO: 1105, and the VL contains the amino acid sequence of SEQ ID NO: 1148, or The VH contains the amino acid sequence of SEQ ID NO: 1106, and the VL contains the amino acid sequence of SEQ ID NO: 1149, or The VH contains the amino acid sequence of SEQ ID NO: 1107, and the VL contains the amino acid sequence of SEQ ID NO: 1150, or The VH contains the amino acid sequence of SEQ ID NO: 1108, and the VL contains the amino acid sequence of SEQ ID NO: 1151, or The VH contains the amino acid sequence of SEQ ID NO: 1109, and the VL contains the amino acid sequence of SEQ ID NO: 1152, or The VH contains the amino acid sequence of SEQ ID NO: 1415, and the VL contains the amino acid sequence of SEQ ID NO: 1440, or The VH contains the amino acid sequence of SEQ ID NO: 1416, and the VL contains the amino acid sequence of SEQ ID NO: 1441, or The VH contains the amino acid sequence of SEQ ID NO: 1417, the VL contains the amino acid sequence of SEQ ID NO: 1442, or, The VH contains the amino acid sequence of SEQ ID NO: 1418, the VL contains the amino acid sequence of SEQ ID NO: 1443, or, The VH contains the amino acid sequence of SEQ ID NO: 1419, the VL contains the amino acid sequence of SEQ ID NO: 1444, or, The VH contains the amino acid sequence of SEQ ID NO: 1420, the VL contains the amino acid sequence of SEQ ID NO: 1445, or, The VH contains the amino acid sequence of SEQ ID NO: 1421, the VL contains the amino acid sequence of SEQ ID NO: 1446, or, The VH contains the amino acid sequence of SEQ ID NO: 1422, the VL contains the amino acid sequence of SEQ ID NO: 1447, or, The VH contains the amino acid sequence of SEQ ID NO: 1423, the VL contains the amino acid sequence of SEQ ID NO: 1448, or, The VH contains the amino acid sequence of SEQ ID NO: 1424, the VL contains the amino acid sequence of SEQ ID NO: 1449, or, The VH contains the amino acid sequence of SEQ ID NO: 1425, the VL contains the amino acid sequence of SEQ ID NO: 1450, or, The VH contains the amino acid sequence of SEQ ID NO: 1426, the VL contains the amino acid sequence of SEQ ID NO: 1451, or, The VH contains the amino acid sequence of SEQ ID NO: 1427, the VL contains the amino acid sequence of SEQ ID NO: 1452, or, The VH contains the amino acid sequence of SEQ ID NO: 1428, the VL contains the amino acid sequence of SEQ ID NO: 1453, or, The VH contains the amino acid sequence of SEQ ID NO: 1429, the VL contains the amino acid sequence of SEQ ID NO: 1454, or, The VH contains the amino acid sequence of SEQ ID NO: 1430, the VL contains the amino acid sequence of SEQ ID NO: 1455, or The VH contains the amino acid sequence of SEQ ID NO: 1431, the VL contains the amino acid sequence of SEQ ID NO: 1456, or The VH contains the amino acid sequence of SEQ ID NO: 1432, the VL contains the amino acid sequence of SEQ ID NO: 1457, or The VH contains the amino acid sequence of SEQ ID NO: 1433, the VL contains the amino acid sequence of SEQ ID NO: 1458, or The VH contains the amino acid sequence of SEQ ID NO: 1434, the VL contains the amino acid sequence of SEQ ID NO: 1459, or The VH contains the amino acid sequence of SEQ ID NO: 1435, the VL contains the amino acid sequence of SEQ ID NO: 1460, or The VH contains the amino acid sequence of SEQ ID NO: 1436, the VL contains the amino acid sequence of SEQ ID NO: 1461, or The VH contains the amino acid sequence of SEQ ID NO: 1437, the VL contains the amino acid sequence of SEQ ID NO: 1462, or The VH contains the amino acid sequence of SEQ ID NO: 1438, the VL contains the amino acid sequence of SEQ ID NO: 1463, or The VH contains the amino acid sequence of SEQ ID NO: 1439, the VL contains the amino acid sequence of SEQ ID NO: 1464, An anti-Gal3 antibody or a binding fragment thereof.

10. (1) A heavy chain variable region (VH); and (2) A light chain variable region (VL), an anti-Gal3 antibody or a binding fragment thereof, wherein The VH is encoded by the nucleic acid sequence of SEQ ID NO: 547, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 629, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 613, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 695, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 797, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 798, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 866, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 881, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 867, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 882, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 868, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 883, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 869, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 884, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 870, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 885, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 871, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 886, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 872, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 887, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 873, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 888, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 874, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 889, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 875, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 890, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 876, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 891, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 877, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 892, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 878, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 893, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 879, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 894, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 880, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 895, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1011, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1025, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1012, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1026, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1013, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1027, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1014, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1028, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1015, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1029, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1016, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1030, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1017, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1031, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1018, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1032, or The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1019, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1033, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1020, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1034, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1021, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1035, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1022, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1036, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1023, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1037, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1024, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1038, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1239, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1282, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1240, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1283, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1241, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1284, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1242, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1285, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1243, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1286, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1244, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1287, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1245, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1288, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1246, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1289, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1247, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1290, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1248, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1291, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1249, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1292, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1250, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1293, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1251, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1294, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1252, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1295, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1253, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1296, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1254, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1297, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1255, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1298, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1256, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1299, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1257, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1300, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1258, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1301, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1259, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1302, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1260, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1303, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1261, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1304, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1262, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1305, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1263, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1306, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1264, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1307, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1265, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1308, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1266, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1309, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1267, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1310, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1268, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1311, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1269, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1312, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1270, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1313, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1271, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1314, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1272, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1315, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1273, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1316, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1274, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1317, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1275, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1318, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1276, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1319, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1277, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1320, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1278, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1321, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1279, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1322, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1280, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1323, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1281, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1324, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1515, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1540, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1516, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1541, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1517, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1542, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1518, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1543, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1519, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1544, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1520, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1545, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1521, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1546, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1522, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1547, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1523, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1548, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1524, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1549, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1525, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1550, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1526, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1551, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1527, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1552, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1528, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1553, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1529, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1554, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1530, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1555, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1531, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1556, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1532, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1557, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1533, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1558, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1534, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1559, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1535, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1560, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1536, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1561, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1537, and the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1562, or, The VH is encoded by the nucleic acid sequence of SEQ ID NO: 1538, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1563, or, the VH is encoded by the nucleic acid sequence of SEQ ID NO: 1539, the VL is encoded by the nucleic acid sequence of SEQ ID NO: 1564, an anti-Gal3 antibody or a binding fragment thereof. **Claim 11** (1) A heavy chain variable region comprising V Ｈ -CDR1, V Ｈ -CDR2, and V Ｈ -CDR3; and (2) A light chain variable region comprising V Ｌ -CDR1, V Ｌ -CDR2, and V Ｌ -CDR3, wherein the anti-Gal3 antibody or a binding fragment thereof comprises: the V Ｈ -CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 32, 37, or 66; the V Ｈ -CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 801, 951, 952, 77, or 108; the V Ｈ -CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 953, 954, 802, 118, or 164; the V Ｌ -CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 32, 37, or 66;-CDR1 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 171, 178, or 215; said V Ｌ -CDR2 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 222, 229, or 225; said V Ｌ -CDR3 comprises an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 257, 256, or 291, an anti-Gal3 antibody or a binding fragment thereof.

12. The anti-Gal3 antibody or a binding fragment thereof according to any one of claims 1 to 11, wherein the anti-Gal3 antibody or a binding fragment thereof binds to one or more of SEQ ID NOs: 3 to 26.

13. The anti-Gal3 antibody or a binding fragment thereof according to any one of claims 1 to 11, wherein the anti-Gal3 antibody or a binding fragment thereof selectively binds to the N-terminal domain of Gal3.

14. The anti-Gal3 antibody or its binding fragment is 20H5.A3, 2D10.2B2, F847C.21H6, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, 2D10.2B2-v2, 2D10-VH0-NDA-VL0, 2D10-VH0-QDT-VL0, 2D10-VH0-SDT-VL0, 2D10-VH0-v1-QDT, 2D10-VH0-v2-QDT, 2D10-hVH1-hVL1, 2D10-hVH1-hVL2, 2D10-hVH1-hVL3, 2D10-hVH1-hVL4, 2D10-hVH2-hVL1, 2D10-hVH2-hVL2, 2D10-hVH2-hVL3, 2D10-hVH2-hVL4, 20H5.A3-hIgG4(S228P), 20H5.A3-hIgG4(S228P)-mv2, 798-9.20H5.A3-mH0mL1, 798-9.20H5.A3-mH1mL0, 798-9.20H5.A3-mH1mL1, 798-9.20H5.A3-mH2mL0, 798-9.20H5.A3-mH2mL1, 20H5.A3-VH1VL1, 20H5.A3-VH1VL2, 20H5.A3-VH1VL3, 20H5.A3-VH1VL4, 20H5.A3-VH1VL5, 20H5.A3-VH1VL6, 20H5.A3-VH2VL3, 20H5.A3-VH2VL4, 20H5.A3-VH2VL5, 20H5.A3-VH2VL6, 20H5.A3-VH3VL5, 20H5.A3-VH3VL6, 20H5.A3-VH4VL3, 20H5.A3-VH4VL4, 20H5.A3-VH4VL5, 20H5.A3-VH4VL6, 20H5.A3-VH5VL5, 20H5.A3-VH5VL6, 20H5.A3-VH6VL4, 20H5.A3-VH6VL5, 20H5.A3-VH6VL6, 20H5.A3-VH7VL1, 20H5.A3-VH7V. An anti-Gal3 antibody or a binding fragment thereof according to any one of claims 1 to 11, selected from the group consisting of L2, 20H5.A3-VH7VL3, 20H5.A3-VH7VL4, 20H5.A3-VH7VL5, 20H5.A3-VH7VL6, 20H5.A3_hVH3VL1-hIgG1 (KEMv2), 20H5.A3_hVH3VL1-hIgG1 (LALAPGv2), 20H5.A3_hVH3VL1-hIgG1 (REM), 20H5.A3_hVH5VL1-hIgG1 (KEMv2), 20H5.A3_hVH5VL1-hIgG1 (LALAPGv2), 20H5.A3_hVH5VL1-hIgG1 (REM), 20H5.A3_hVH6VL1-hIgG1 (KEMv2), 20H5.A3_hVH6VL1-hIgG1 (LALAPGv2), 20H5.A3_hVH6VL1-hIgG1 (REM), 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or a binding fragment thereof.

15. Use of an anti-Gal3 antibody or a binding fragment thereof according to any one of claims 1 to 11 in the manufacture of a medicament for a method of enhancing the translocation of glucose transporter (GLUT) in cells, wherein the method comprises: contacting the cells with an anti-Gal3 antibody or a binding fragment thereof, comprising, wherein, in the cells, binding of the anti-Gal3 antibody or a binding fragment thereof to Gal3 inhibits the blockade of GLUT4 translocation via Gal3. Use of an anti-Gal3 antibody or a binding fragment thereof according to any one of claims 1 to 11 in the manufacture of a medicament for a method of enhancing the translocation of glucose transporter (GLUT) in cells, wherein the method comprises contacting the cells with a complex formed by pre-incubating the cells with Gal3 and the anti-Gal3 antibody or a binding fragment thereof Use, comprising

17. Use of an anti-Gal3 antibody or a binding fragment thereof according to any one of claims 1 to 11 in the manufacture of a medicament for a method of improving insulin sensitivity in a subject in need thereof, wherein the method comprises administering the anti-Gal3 antibody or a binding fragment thereof to the subject comprising in the subject, binding of the anti-Gal3 antibody or a binding fragment thereof to Gal3 inhibits the blockade of translocation of glucose transporter (GLUT) via Gal3 in the subject, thereby improving insulin sensitivity in the subject Use

18. Use of an anti-Gal3 antibody or a binding fragment thereof according to any one of claims 1 to 11 in the manufacture of a medicament for a method of improving insulin sensitivity in a subject in need thereof, wherein the method comprises administering to the subject a complex formed by pre-incubating Gal3 and the anti-Gal3 antibody or a binding fragment thereof, thereby improving insulin sensitivity in the subject Use, comprising

19. Use of an anti-Gal3 antibody or a binding fragment thereof according to any one of claims 1 to 11 in the manufacture of a medicament for a method of treating a disease associated with insulin resistance in a subject in need thereof, wherein the method comprises Administering an anti-Gal3 antibody or a binding fragment thereof to the subject, thereby treating a disease associated with insulin resistance in the subject, Use comprising.

20. Use of an anti-Gal3 antibody or a binding fragment thereof according to any one of claims 1 to 11 in the manufacture of a medicament for a method of treating a disease associated with insulin resistance in a subject in need thereof, wherein the method comprises: Treating a disease associated with insulin resistance in the subject by administering to the subject a pre-incubated complex of Gal3 and an anti-Gal3 antibody or a binding fragment thereof, Use comprising.

21. The use according to claim 19, wherein the disease associated with insulin resistance is type 2 diabetes, chronic hyperinsulinemia, metabolic syndrome, type A insulin resistance, type B insulin resistance, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular disease, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer-related diabetes (PCDM), or cancer.

22. The use according to claim 17, further comprising identifying a subject in need of treatment for a disease associated with insulin resistance before the administration step.

23. The use according to claim 17, further comprising detecting an improvement in a disease associated with insulin resistance after the administration step.

24. The use according to claim 23, wherein detecting an improvement in a disease associated with insulin resistance comprises detecting an improvement in insulin sensitivity in the subject.

25. The detection of improvement in insulin sensitivity in the subject is performed by measuring blood glucose level, measuring blood insulin level, glucose tolerance test, or euglycemic hyperinsulinemic clamp method, the use according to claim 24.

26. The insulin sensitivity in the subject is improved by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% as compared with the insulin sensitivity of the subject before the administration step, the use according to claim 17.

27. The complex formed by pre-incubating the Gal3 with the anti-Gal3 antibody or its binding fragment is in a mass ratio of 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, or 1:2.5, or approximately the mass ratio, or any mass ratio within the range defined by any two of the mass ratios, of Gal3 and the anti-G al3 antibody or its binding fragment, the use according to claim 15. **Claim 28**: The use according to claim 15, wherein the complex is prepared by pre-incubating Gal3 with an anti-Gal3 antibody or a binding fragment thereof at a concentration of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 μg / mL, or approximately that concentration, or any concentration within the range defined by any two of said concentrations of Gal3, and at a concentration of 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 μg / mL, or approximately that concentration, or any concentration within the range defined by any two of said concentrations of the anti-Gal3 antibody or its binding fragment. **Claim 29**: The use according to claim 15, wherein the glucose transporter is glucose transporter 1 (GLUT1) and / or glucose transporter 4 (GLUT4). **Claim 30**: The use according to claim 15, wherein the method is carried out in vitro or in vivo. **Claim 31**: The GLUT translocation in the cells is enhanced by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 105%, 110%, 115%, 120%, 125%, 130%, 135%, 140%, 145%, 150%, 155%, 160%, 165%, 170%, 175%, 180%, 185%, 190%, 195%, or 200% as compared to cells not contacted with the anti-Gal3 antibody or a binding fragment thereof after being contacted with the anti-Gal3 antibody or a binding fragment thereof. The use according to claim 15.

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