Anti-Gal3 antibodies and methods of use

Abstract

Disclosed herein are antibodies and compositions for binding to Gal3. Some embodiments allow for disruption of the interaction between galectin-3 (Gal3) and cell surface markers and / or proteins associated with neurological diseases and / or primary diseases, such as Alzheimer's disease. Furthermore, disclosed herein is an antibody or a binding fragment thereof for the treatment of fibrosis, hepatic fibrosis, renal fibrosis, cardiac fibrosis, pulmonary fibrosis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, sepsis, atopic dermatitis, psoriasis, cancer, brain cancer, breast cancer, colorectal cancer, kidney cancer, liver cancer, lung cancer, pancreatic cancer, bladder cancer, gastric cancer, malignant hematologic tumor, methods and uses for the treatment of nervous system diseases and / or primary diseases. Furthermore, some embodiments provided herein may traverse the blood-brain barrier, and may be conjugated or otherwise combined with one or more loadings for use in the treatment of neurological diseases.

Description

[0001] This application is a divisional application of the Chinese patent application with application number 202180022171.2, application date January 12, 2021, and invention name “Anti-Gal3 Antibodies and Methods of Use”. CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 960,300 filed on January 13, 2020, U.S. Provisional Patent Application No. 63 / 024,327 filed on May 13, 2020, U.S. Provisional Patent Application No. 63 / 092,069 filed on October 15, 2020, and U.S. Provisional Patent Application No. 63 / 122,409 filed on December 7, 2020, each of which is expressly incorporated herein by reference in its entirety, including any appendices filed therewith. References to sequence listings

[0003] This application is submitted with a sequence listing in electronic format. The sequence listing is provided as a file entitled SeqListingIMMUT027WO.TXT, which was created and last modified on January 12, 2021, and is 875,600 bytes in size. The information in the electronic sequence listing is incorporated herein by reference in its entirety. Technical Field

[0004] Aspects of the present disclosure generally relate to antibodies or binding fragments thereof that bind to galectin-3 (Gal3). These antibodies or binding fragments thereof can block or disrupt the interaction between Gal3 and cell surface markers and / or proteins associated with neurological disorders and / or underlying diseases. These antibodies or binding fragments thereof can also cross the blood-brain barrier. Background Art

[0005] Galectin-3 (Gal3, GAL3) is a lectin or carbohydrate-binding protein that is specific for β-galactosides. In human cells, Gal3 is expressed and 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

[0006] Disclosed herein are embodiments involving anti-Gal3 antibodies, binding fragments thereof, and / or antigen binding molecules. In some embodiments, any such structure can be used to block the interaction between Gal3 and a cell surface marker.

[0007] In some embodiments, these cell surface markers are associated with a disease (e.g., cancer or fibrosis). In some embodiments, any such structure prevents abnormal folding or accumulation of proteins. In some embodiments, any such structure can be used to treat neurological disorders, such as but not limited to Alzheimer's disease.

[0008] In some embodiments, any such structure can be used to assist in crossing the blood-brain barrier.In some embodiments, the items can be associated with one or more payloads.

[0009] Disclosed herein is an anti-Gal3 antibody or a binding fragment thereof, which comprises (1) a heavy chain variable region comprising V H -CDR1, V H -CDR2 and V H - CDR3, and (2) light chain variable region, which includes V L -CDR1, V L -CDR2 and V L -CDR3. In some embodiments, V H - CDR1 comprises an amino acid sequence selected from SEQ ID NO: 36-44, 588-615. In some embodiments, V H -CDR2 comprises an amino acid sequence selected from SEQ ID NO: 54-60, 616-643. In some embodiments, V H -CDR3 comprises an amino acid sequence selected from SEQ ID NO: 70-81, 644-671. In some embodiments, V L - CDR1 comprises an amino acid sequence selected from SEQ ID NO: 92-101, 672-699. In some embodiments, V L -CDR2 comprises an amino acid sequence selected from SEQ ID NO: 111-116, 700-727. In some embodiments, V L - CDR3 comprises an amino acid sequence selected from SEQ ID NOs: 127-135, 728-755.

[0010] Also disclosed herein are methods of treating a neurological disorder in a subject in need thereof. In some embodiments, the method comprises administering to the subject an effective amount of an anti-Gal3 antibody or binding fragment thereof, thereby treating the neurological disorder in the subject.

[0011] Also disclosed herein are methods for disrupting the binding between Gal3 and APP or Aβ, or both. In some embodiments, the method comprises contacting APP or Aβ, or both, with an anti-Gal3 antibody or binding fragment thereof, thereby disrupting the binding between Gal3 and APP.

[0012] Also disclosed herein are methods of treating a primary disease in a subject in need thereof. In some embodiments, the method comprises administering to the subject an effective amount of an anti-Gal3 antibody or binding fragment thereof, thereby treating the primary disease in the subject.

[0013] Also disclosed herein are methods of administering an antibody to a subject. In some embodiments, the method comprises administering an anti-Gal3 antibody or a binding fragment thereof to a subject.

[0014] Also disclosed herein are methods of promoting neuronal regeneration in a subject in need thereof. In some embodiments, the method comprises administering to the subject an effective amount of an anti-Gal3 antibody or binding fragment thereof, thereby promoting neuronal regeneration in the subject.

[0015] Also disclosed herein are methods for disrupting the binding between Gal3 and a cell surface receptor. In some embodiments, the method comprises contacting Gal3 with an anti-Gal3 antibody or a binding fragment thereof, thereby disrupting the binding between Gal3 and the cell surface receptor.

[0016] Also disclosed herein are methods for treating a disease (such as an inflammatory disease, cancer, and / or fibrosis) in a subject in need thereof. In some embodiments, the disease comprises fibrosis, liver fibrosis, kidney fibrosis, cardiac fibrosis, pulmonary fibrosis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, sepsis, atopic dermatitis, psoriasis, cancer, brain cancer, breast cancer, colorectal cancer, kidney cancer, liver cancer, lung cancer, pancreatic cancer, bladder cancer, gastric cancer, or a hematological malignancy. In some embodiments, the method comprises administering to the subject an effective amount of an anti-Gal3 antibody or a binding fragment thereof, thereby treating the subject's disease.

[0017] Also disclosed herein are uses of anti-Gal3 antibodies or binding fragments thereof for treating a disease (such as an inflammatory disease, cancer, and / or fibrosis) in a subject in need thereof.

[0018] Also disclosed herein are uses of anti-Gal3 antibodies or binding fragments thereof for treating a neurodegenerative disease in a subject in need thereof.

[0019] Also disclosed herein is the use of an anti-Gal3 antibody or binding fragment thereof for treating a primary disease in a subject in need thereof.

[0020] Also disclosed herein is the use of an anti-Gal3 antibody or a binding fragment thereof for promoting neuronal regeneration in a subject in need thereof.

[0021] Antibody conjugates are also disclosed herein. In some embodiments, the antibody conjugate comprises an anti-Gal3 antibody or a binding fragment thereof and a payload conjugated to the anti-Gal3 antibody or a binding fragment thereof. In some embodiments, the antibody conjugate is capable of crossing the blood-brain barrier. In some embodiments, the barrier is located in a subject whose blood-brain barrier is weakened or altered due to a disease that affects the blood-brain barrier (e.g., reduces the structural integrity of the barrier).

[0022] Also disclosed herein are multispecific antibodies.In some embodiments, the multispecific antibody comprises a first binding domain that binds to Gal3 and a second binding domain that binds to a therapeutic target molecule located in the brain of a subject.

[0023] Also disclosed herein are methods for delivering a load to the central nervous system of a subject in need thereof. In some embodiments, the method comprises administering to the subject an antibody conjugate comprising an anti-Gal3 antibody or a binding fragment thereof and a load conjugated to the anti-Gal3 antibody or a binding fragment thereof, wherein the antibody conjugate is capable of crossing the blood-brain barrier. In some embodiments, the barrier is located in a subject whose blood-brain barrier is weakened or altered due to a disease that affects the blood-brain barrier (e.g., reduces the structural integrity of the barrier).

[0024] Also disclosed herein are methods for increasing the permeability of a cargo through the blood-brain barrier of a subject in need thereof. In some embodiments, the method comprises conjugating an anti-Gal3 antibody or a binding fragment thereof to a cargo to form an antibody conjugate. In some embodiments, the barrier is located in a subject whose blood-brain barrier is weakened or altered due to a disease that affects the blood-brain barrier (e.g., reduces the structural integrity of the barrier).

[0025] Also disclosed herein is the use of an anti-Gal3 antibody or binding fragment thereof to assist in carrying cargo across the blood-brain barrier of a subject.

[0026] Also disclosed herein are methods of disrupting the interaction between Gal3 and the transforming growth factor beta (TGF-b) receptor.

[0027] Also disclosed herein are methods of treating fibrosis in a subject in need thereof.

[0028] Also disclosed herein are methods of treating non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in a subject in need thereof.

[0029] Also disclosed herein are methods of treating an immune-related disorder in a subject in need thereof.

[0030] Also disclosed herein are methods for disrupting the interaction between Gal3 and tumor cell surface markers.

[0031] Also disclosed herein are methods of treating cancer in a subject in need thereof.

[0032] Also disclosed herein are methods for identifying antibodies or binding fragments thereof that are capable of disrupting the interaction between Gal3 and a TGF-b receptor, a cell surface marker, or a tumor cell surface marker.

[0033] Also disclosed herein are pharmaceutical compositions or drugs. In some embodiments, the pharmaceutical composition or drug comprises any anti-Gal3 antibody or its binding fragment, any antibody conjugate or any multispecific antibody disclosed herein and at least one pharmaceutically acceptable diluent, excipient or carrier. In some embodiments, the composition or drug is used to treat fibrosis, liver fibrosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), renal fibrosis, cardiac fibrosis, arterial fibrosis, venous thrombosis or pulmonary fibrosis. In some embodiments, the composition or drug is used to treat cancer. In some embodiments, the composition or drug is used to treat immune-related disorders.

[0034] Also disclosed herein is the use of an anti-Gal3 antibody or a binding fragment thereof for treating fibrosis, liver fibrosis, NAFLD, NASH, renal fibrosis, cardiac fibrosis, arterial fibrosis, venous thrombosis, or pulmonary fibrosis.

[0035] Also disclosed herein is the use of an anti-Gal3 antibody or a binding fragment thereof for treating cancer.

[0036] Also disclosed herein is the use of an anti-Gal3 antibody or a binding fragment thereof for inhibiting tumor cell growth in vitro.

[0037] Also disclosed herein is the use of an anti-Gal3 antibody or a binding fragment thereof for slowing the growth of a brain tumor.

[0038] Also disclosed herein are antibodies that bind to human Gal3 and compete with an anti-Gal3 antibody or binding fragment thereof for binding to human Gal3. In some embodiments, the antibody competes with any one of the anti-Gal3 antibodies or binding fragments disclosed herein.

[0039] Also disclosed herein are methods for identifying antibodies or binding fragments capable of disrupting the interaction between Gal3 and the TGF-b receptor.

[0040] Also disclosed herein are antibodies or binding fragments thereof that bind to the N-terminal domain and / or TRD of Gal3.

[0041] Also disclosed herein are proteins comprising Figure 18-27 One or more peptide sequences having at least 80%, 85%, 90%, 95%, 99% or 100% homology to one or more peptide sequences. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] In addition to the above features, other features and changes will be apparent from the following drawings and description of exemplary embodiments. It should be understood that these drawings depict typical embodiments and are not intended to limit the scope.

[0043] Figure 1 Depicted is a graphic representation of the evaluation of the relative binding affinity of APP695 to galectin-3 (GAL3) from different sources as measured by enzyme-linked immunosorbent assay (ELISA).

[0044] Figure 2 Depicted is a graphical representation of the evaluation of the relative binding affinity of APP695 and GAL3 after blocking by anti-Gal3 antibodies as measured by ELISA.

[0045] Figure 3 Depicted are the results of a hippocampus-dependent memory test (Morris water maze) of APPSwe transgenic mice and wild-type control mice treated with isotype control or anti-Gal3 antibody (TB001) before and after antibody treatment.

[0046] Figure 4 Depicted is a graphic representation of the number of crossings during the probe test phase of the Morris water maze for APPSwe transgenic animals and wild-type controls.

[0047] Figure 5A Depicted are the results of analysis of Aβ protein levels in brain tissues of APPSwe transgenic and wild-type mice as determined by immunoblotting using a monoclonal Aβ-specific sequence-dependent antibody (6E10).

[0048] Figure 5B Depicted are the Figure 5A A graphic representation of the intensity of the bands.

[0049] Figure 5C Depicted are the results of analysis of mTB001 in brain tissue of APPSwe transgenic and wild-type mice measured by ELISA.

[0050] Figure 6A -B shows the results of Morris water maze test of Aβ42 fibril-injected mice treated with isotype control or anti-Gal3 antibody (TB001) and wild-type (uninjected) controls before (6A) and after (6B) antibody treatment.

[0051] Figure 7Depicted is a graphic representation of the number of crossings during the probe phase of the Morris water maze test in Aβ42 fibril-injected mice treated with isotype control or anti-Gal3 antibody (TB001) and wild-type (uninjected) controls.

[0052] Figure 8A Depicted is a graphic representation of the results of immunohistochemical staining levels of Aβ with 6E10 antibody in mouse brain tissues quantified by NIH Image J software.

[0053] Figure 8B A graphic representation depicts the results of immunohistochemical staining levels of NeuN in mouse brain tissues quantified by NIH Image J software.

[0054] Figure 8C A graphic representation depicts the results of immunohistochemical staining levels of phosphorylated Tau in mouse brain tissues quantified by NIH Image J software.

[0055] Figure 8D A graphic representation depicts the results of immunohistochemical staining levels of Iba-1 in mouse brain tissues quantified by NIH Image J software.

[0056] Figure 8E A graphic representation depicts the results of immunohistochemical staining levels of galectin-3 in mouse brain tissues quantified by NIH Image J software.

[0057] Figure 9 Depicted are graphic representations of immunoblot band intensities of Aβ protein levels in brain tissues of Aβ42 fibril-injected and wild-type mice analyzed by Image J software.

[0058] Figure 10A -B depicts a graphical representation of the evaluation of the relative binding affinity of Aβ42 peptide (10A) or Aβ42 oligomer (10B) to Gal3 from different sources as measured by ELISA.

[0059] Figure 11A -B depicts a graphical representation of the evaluation of the relative binding affinity of Aβ42 peptide (11A) or Aβ42 oligomer (11B) after blockade by anti-Gal3 antibody as measured by ELISA.

[0060] Figure 11C Depicted is a graphical representation comparing the efficiency of blocking the interaction between Aβ42 and Gal3 by anti-Gal3 antibodies (TB001 and TB006) or the small molecule Gal3 inhibitor TD139.

[0061] Figure 12ADepicted is a graphic representation of the evaluation of the relative binding affinity of TLR4 to Gal3 from different sources as measured by ELISA.

[0062] Figure 12B Depicted is a graphic representation of the evaluation of the relative binding affinity of TLR4 and Gal3 after blockade by anti-Gal3 antibodies as measured by ELISA.

[0063] Figure 13A Depicted is a graphic representation of the evaluation of the relative binding affinity of TREM2 to Gal3 from different sources as measured by ELISA.

[0064] Figure 13B Depicted is a graphic representation of the evaluation of the relative binding affinity of TREM2 and Gal3 after blocking by anti-Gal3 antibodies as measured by ELISA.

[0065] Figure 14A Depicted is a graphic representation of the evaluation of the relative binding affinity of Tau oligomers and Gal3 after blocking by anti-Gal3 antibodies as measured by ELISA.

[0066] Figure 14B Depicted is a graphic representation of the evaluation of the relative binding affinity of Tau oligomers to Gal3 from different sources as measured by ELISA.

[0067] Figure 15A Depicted is a graphic representation of the evaluation of the relative binding affinity of α-synuclein and Gal3 after blockade by anti-Gal3 antibodies as measured by ELISA.

[0068] Figure 15B Depicted is a graphic representation of the evaluation of the relative binding affinity of α-synuclein to Gal3 from different sources as measured by ELISA.

[0069] Figure 16 Depicted are the protein sequences of Gal3, amyloid-β precursor protein (APP) isoform c (APP695), amyloid-β peptide (1-42), TGF-β receptor, and other indicated protein sequences.

[0070] Figure 17 The peptide sequence of Gal3 used for generating and analyzing antibodies is depicted.

[0071] Figure 18 Depicted are exemplary variable heavy chain complementarity determining regions (CDR) 1 for the anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein can include one or more CDRs provided herein.

[0072] Figure 19Depicted are exemplary variable heavy chain CDR2s for the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more CDRs provided herein.

[0073] Figure 20 Depicted are exemplary variable heavy chain CDR3s for the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more CDRs provided herein.

[0074] Figure 21 Depicted are exemplary variable light chain CDR1s for the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more CDRs provided herein.

[0075] Figure 22 Depicted are exemplary variable light chain CDR2s for the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more CDRs provided herein.

[0076] Figure 23 Depicted are exemplary variable light chain CDR3s for the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more CDRs provided herein.

[0077] Figure 24 Depicted are exemplary heavy chain variable region sequences for the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more VH sequences provided herein.

[0078] Figure 25 Depicted are exemplary light chain variable region sequences for the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more VL sequences provided herein.

[0079] Figure 26 Depicted are exemplary heavy chain sequences for use with the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more heavy chain sequences provided herein.

[0080] Figure 27 Depicted are exemplary light chain sequences for use with the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more light chain sequences provided herein.

[0081] Figure 28Depicted are exemplary combinations of variable heavy chain CDR1, CDR2, and CDR3 of the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more heavy chain CDR combinations provided herein.

[0082] Figure 29 Depicted are exemplary combinations of variable light chain CDR1, CDR2, and CDR3 for the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more light chain CDR combinations provided herein.

[0083] Figure 30 Depicted are exemplary combinations of heavy and light chain CDRs for the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more heavy and light chain CDR combinations provided herein.

[0084] Figure 31 Depicted are exemplary combinations of heavy and light chain variable regions of the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more heavy and light chain variable region combinations provided herein.

[0085] Figure 32 Depicted are exemplary combinations of heavy and light chains of the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more heavy and light chains provided herein.

[0086] Figure 33 Depicted are peptides found to bind to exemplary antibodies disclosed herein (according to Figure 17 and discussed herein) and binning of these exemplary antibodies.

[0087] Figure 34A Depicted are plasma concentrations of exemplary anti-Gal3 antibodies conjugated to biotin in C57BL6 mice implanted with GL261-LUC murine glioblastoma tumors four days after intravenous administration of the anti-Gal3 antibodies.

[0088] Figure 34B Depicted are the concentrations of exemplary anti-Gal3 antibodies conjugated to biotin found in tumor and normal brain tissue of C57BL6 mice transplanted with GL261-LUC murine glioblastoma tumors four days after intravenous administration of the anti-Gal3 antibodies.

[0089] Figure 34CDepicted are the relative concentrations of biotin-conjugated anti-Gal3 antibodies found in tumor or normal brain tissue of C57BL6 mice transplanted with GL261-LUC murine glioblastoma tumors compared to their respective plasma four days after intravenous administration of the anti-Gal3 antibodies.

[0090] Figure 34D Depicted are immunoblots of the apoptosis marker PARP and GAPDH loading control in brain tumor lysates isolated from C57BL6 mice implanted with GL261-LUC murine glioblastoma tumors following intravenous administration of anti-Gal3 antibodies.

[0091] Figure 34E Depicted is a graphic representation of the relative amount of PARP normalized to the GAPDH loading control quantified from the immunoblots of FIG. 34 .

[0092] Figure 35 Depicted are alignments of some embodiments of VH CDR or VL CDR regions of various embodiments of anti-Gal3 antibodies.In some embodiments, any method or composition provided herein can utilize any 1, 2, 3, 4, 5, 6, or 7 consensus CDRs provided herein.

[0093] Figure 36 Depicted are KD (M) values ​​for Gal3 binding of exemplary anti-Gal3 antibodies disclosed herein.

[0094] Figure 37 Depicted are nucleic acid sequences encoding exemplary heavy chain variable regions of the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more heavy chain variable regions encoded by a nucleic acid provided herein.

[0095] Figure 38 Depicted are nucleic acid sequences encoding exemplary light chain variable regions of the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more light chain variable regions encoded by a nucleic acid provided herein.

[0096] Figure 39 Depicted are nucleic acid sequences encoding exemplary heavy chains of the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more heavy chains encoded by a nucleic acid provided herein.

[0097] Figure 40 Depicted are nucleic acid sequences encoding exemplary light chains of the anti-Gal3 antibodies disclosed herein.In some embodiments, any composition or method provided herein can include one or more light chains encoded by a nucleic acid provided herein.

[0098] Figure 41ADepicted is a graphical representation of the evaluation of the relative binding affinity of transforming growth factor beta (TGF-b) receptor type 1 (TGFBR1), TGF-b receptor type 2 (TGFBR2), TGF-b receptor type 3 (TGFBR3), or a combination thereof to galectin-3 (GAL3) as measured by enzyme-linked immunosorbent assay (ELISA).

[0099] Figure 41B Depicted are the binding kinetics of the interaction between Gal3 and TGF-b receptor measured by surface plasmon resonance.

[0100] Figure 42 Depicted is a graphic representation of the evaluation of the relative binding affinity of TGFBR1 and GAL3 after blocking by anti-Gal3 antibodies as measured by ELISA.

[0101] Figure 43A Depicted is a graphic representation of the evaluation of the relative expression of genes associated with fibrosis in LX2 cells treated with either TGF-b and a murine anti-GAL3 antibody or a vehicle control as measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

[0102] Figure 43B Depicted is a graphic representation of the evaluation of the relative expression of genes associated with fibrosis in LX2 cells treated with either TGF-b and humanized anti-Gal3 antibody or vehicle control as measured by qRT-PCR.

[0103] Figure 44A -D depicts a graphical representation of the evaluation of the relative binding affinity of (A) VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb; (B) ErbB2, HGFR(cMet), TNF sRI, CTLA4, CD47, PD-L1; (C) FGFR1α-IIIb; (D) FGFR1α-IIIc, FGFR2α-IIIc, FGFR IIIc, FGFR4 to galectin-3 as measured by enzyme-linked immunosorbent assay (ELISA).

[0104] Figure 44E Depicted is a graphical representation of the determination of the binding affinity of VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, and ErbB2 to Gal3 as determined by SPR.

[0105] Figure 45A-E depicts a graphical representation of the evaluation of the relative binding affinity of tumor surface receptors (A) EGFR, (B) VEGFR2, (C) VEGFR3, (D) PDGFRa, (E) PDGFRb to Gal3 after blockade by anti-Gal3 antibodies as measured by ELISA.

[0106] Figure 46A -B depicts a graphical representation of the determination of the binding affinity of anti-Gal3 antibodies (A) clone 6H6 and (B) clone 2D10 to full-length recombinant human Gal3 (rhGal3) or the C-terminal domain of Gal3 (Gal3-CRD) measured by SPR.

[0107] Figure 47A -B depicts a graphic representation of the survival percentage of (A) hepatocellular carcinoma (HCC) cells (Hep3B, HepG2) and (B) glioblastoma (GBM) tumor cells (U118) exposed to anti-Gal3 antibodies for 72 hours compared to untreated controls.

[0108] Figure 48 Depicted is a graphic representation of the percent survival of GBM tumor cells (U87MG, U118, LN229 lines) following exposure to control isotype and anti-Gal3 antibody (2D10) alone or with 100 μM temozolomide (TMZ) for 72 hours compared to untreated controls.

[0109] Figure 49 Depicted are graphical representations of tumor progression in GL261-LUC transplanted animals treated with control isotype, TMZ, anti-Gal3 antibody (2D10), or the combination (TMZ+2D10), determined as fold change in luminescence emission (flux per second) after initiation of treatment.

[0110] Figure 50 The antibody affinities (K) of the anti-Gal3 humanized antibodies IMT001 (TB001) and IMT006 (TB006; 4A11.H3L1) to human, macaque, and mouse Gal3 are depicted. D Both humanized IMT001 and IMT006, derived from mouse monoclonal antibodies, have high affinity for human and macaque Gal3, while IMT001 also has high affinity for mouse Gal3.

[0111] Figure 51 Depicted is a graphic representation of the inhibition of TGF-β-induced procollagen production in LX-2 cells when treated with IMT001 (TB001), IMT006 (TB006; 4A11.H3L1), and hIgG4 (isotype control) at increasing concentrations of the antibodies. LX-2 cells were stimulated with TGF-β (10 ng / mL) for 2 hours.

[0112] Figure 52 A graphical representation depicts the inhibition of TGF-β-induced procollagen production and Gal3 expression in LX-2 cells when treated with IMT001 and 4A11.H3L1. TGF-β-stimulated procollagen expression in LX-2 cells is enhanced by exogenous Gal3 and inhibited by IMT006. In response to TGF-β stimulation, Gal3 increases on the LX-2 cell surface (Panel A) and in the culture medium (Panel B). The anti-Gal3 antibody IMT006 reduces procollagen expression following either TGF-β treatment or TGF-β plus rhGal3.

[0113] Figure 53 Depicts the reduction of Gal3 and membrane TGFBR2 expression in LX2 cells transfected with Gal3 short hairpin RNA (shRNA) vectors, and the reduction of membrane TGFbR1 expression in control LX-2 cells treated with IMT001. Due to the knockdown of Gal3, TGFb-R2 and Gal3 expression on the cell surface of LX-2 cells is reduced. LX-2 cells were transfected with short hairpin RNA vectors to silence Gal3 or with control vectors, and single clones were isolated (named LX-shGal3 and LX2-shCon, respectively). After treatment with TGF-b, the expression of Gal3 in LX2-shGal3 was significantly reduced compared to LX2-shCon. Compared to LX2-shCon cells, the expression of TGFbR2 and Gal3 on the cell membrane of LX2-shGal3 cells was reduced. In untransfected LX-2 cells, treatment with IMT001 reduced cell membrane TGFbR1.

[0114] Figure 54 Depicted is a graphic representation of the inhibition of TGF-β-induced procollagen production in LX-2 cells transfected with a Gal3 shRNA vector. Knockdown of Gal3 in LX-2 cells reduces TGF-β-induced procollagen production. TGF-β ECs inhibit procollagen production in the LX2-scramble control. 50 was 1.01 ng / mL and had an effect on TGF-β EC production of procollagen in LX2-shGal3 Gal3-knockdown cells. 50 It is 2.04ng / mL.

[0115] Figure 55 Depicted is a graphical representation of the pharmacokinetics of IMT001 in rats, where the half-life is approximately 2 weeks. The PK of IMT001 in rats is dose proportional with a half-life of approximately 2 weeks.

[0116] Figure 56Depicted is a graphic representation of the tissue distribution of TB006 (IMT006, 4A11.H3L1) in mice following a single injection dose. ELISA was used to measure IMT006 exposure in plasma and tissues.

[0117] Figure 57 A graphical representation of the measurement of total and unbound Gal3 in rat plasma following treatment with IMT001 is depicted. A single dose of IMT001 was administered intravenously at 3 mg / kg (n=3) and 30 mg / kg (n=4). Samples were taken 21 days after dosing. Total rGal3 increased 2.97-fold in SD rats treated with 30 mg / kg IMT001. Unbound rGal3 was approximately 85% lower than total rGal3 in SD rats treated with 30 mg / kg IMT001. Unbound rGal3 was 55% lower after IMT001 treatment compared to untreated rats.

[0118] Figure 58 Depicted is a graphical representation of the transcriptome in methionine-choline deficient (MCD) mice treated with mIMT001 (murine IMT001). Statistical analysis was performed by Student's t-test; *p<0.05, **p<0.01, ***p<0.001. Significantly enriched biological functions (analyzed by clusterProfiler) were observed for genes whose expression was induced in the NASH model and suppressed by antibody treatment (overlap in the Venn diagram).

[0119] Figure 59 Depicted is a graphic representation of Gal3 and TGFbR1 expression in the liver of MCD mice following treatment with mIMT001.

[0120] Figure 60 Depicted is a graphic representation of Gal3 and TGFbR1 expression in the liver of MCD mice following treatment with mIMT001.

[0121] Figure 61 A graphic representation of co-immunoprecipitation analysis of TGFbR1 and TGFbR2 bound to immunoprecipitated Gal3 is depicted. As depicted, 293T cells were transfected with TGFbR1, TGFbR2, and Gal3-FLAG plasmids, either alone or in combination. Cell lysates were collected 24 hours after transfection and analyzed by FLAG IP. Overexpressed Gal3 pulls down TGFbR1 / 2 with high specificity. The upper band in the TGFbR2 blot is glycosylated TGFbR2, and the lower band is non-glycosylated TGFbR2.

[0122] Figure 62A graphic representation of Western blot analysis of Smad3 expression and phosphorylation status in LX-2 cells following TGF-β stimulation. LX2 cells were starved for 24 hours. Cells were exposed to 2 ng / mL TGF-β alone or 2 ng / mL TGF-β in combination with the indicated concentrations of control antibodies, IMT001, or IMT006. Cell lysates were analyzed for SMAD3 and phosphorylated SMAD3 protein levels. GAPDH levels were used as a loading control.

[0123] Figure 63A Depicted is a Western blot showing that Gal3 promotes Aβ aggregation into oligomeric forms. Aβ oligomers were detected with antibody A11, and total Aβ was detected with antibody 6E10.

[0124] Figure 63B Depicted are dot blots of Aβ oligomers incubated with different concentrations of the anti-Gal3 antibody mTB001 (0, 10, 100 μg). The dot blots show that Aβ oligomerization is reversed by the anti-Gal3 antibody. Aβ oligomers were detected with the antibody A11, and total Aβ was detected with the antibody 6E10.

[0125] Figure 63C Depicts the detection of Aβ oligomers using antibody A11 Figure 63B Quantification of dot blots.

[0126] Figure 63D Depicted are dot blots of Aβ oligomers incubated with various anti-Gal3 antibodies disclosed herein. As depicted, the numerical labels correspond to the anti-Gal3 antibodies.

[0127] Figure 64 The antibody names used throughout this disclosure are depicted to refer to the same antibody (having exemplary peptide and nucleic acid sequences provided elsewhere in this disclosure and appropriately identified as at least one of the described names) and may be used interchangeably. The names shown in the columns correspond to the same antibody.

[0128] Figure 65A Dot blot depicts the time course of aggregation of Aβ-42 peptide into oligomeric forms when incubated with various isoforms of Gal3. Isoforms of Gal3 tested included full-length Gal3 (expressed as E. coli), hGal3-R186S, hGal3-P64H, hGal3-65-250 (amino acids 65-250), and hGal3-CRD-His (His-tagged C-terminal domain of Gal3). Lane "0" indicates no Gal3 was added. The time course was performed over 5 hours.

[0129] Figure 65B Depicts Figure 65A Quantification of dot blots.

[0130] Figure 65C Dot blot depicting the time course of aggregation of Aβ-42 peptide into oligomeric forms when incubated with various short peptides of Gal3. Peptides AF (SEQ ID NO: 582-587) were tested. hGal3-65-250 was used as a positive control. DETAILED DESCRIPTION

[0131] Some embodiments provided herein relate to 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.

[0132] Some embodiments provided herein relate to anti-Gal3 antibodies or binding fragments thereof that disrupt the interaction between Gal3 and proteins associated with primary diseases or neurological diseases. In some embodiments, the anti-Gal3 antibodies and binding fragments thereof disclosed herein are methods and uses for treating primary diseases and / or neurological diseases.

[0133] Some embodiments provided herein relate to anti-Gal3 antibodies or binding fragments thereof capable of crossing the blood-brain barrier. In some embodiments, the blood-brain barrier is that of a subject suffering from a neurological disease. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is a multispecific antibody to improve the penetration of another antibody across the blood-brain barrier. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is conjugated to a cargo to improve the penetration of the cargo across the blood-brain barrier.

[0134] Some embodiments provided herein relate to anti-Gal3 antibodies or binding fragments thereof that disrupt the interaction between Gal3 and cell surface markers or tumor cell surface markers. In some embodiments, the anti-Gal3 antibodies and binding fragments thereof disclosed herein are used to treat diseases associated with cell surface markers or tumor cell surface markers. In some embodiments, the disease is cancer, fibrosis, or an immune-related disorder.

[0135] Galectin-3 (Gal3, GAL3) plays an important role in cell proliferation, adhesion, differentiation, angiogenesis, and apoptosis. This activity is due, at least in part, to immunomodulatory properties and binding affinity for other immunomodulatory proteins, signaling proteins, and other cell surface markers. Gal3 functions through distinct N-terminal and C-terminal domains. The N-terminal domain (isoform 1: amino acids 1-111) includes the tandem repeat domain (TRD, isoform 1: amino acids 36-109) and is primarily responsible for the oligomerization of Gal3. The C-terminal domain (isoform 1: amino acids 112-250) includes the carbohydrate recognition binding domain (CRD), which binds to β-galactosides.

[0136] Galectin-3 (Gal3) has been implied to have immunomodulatory activity. An example of this is the interaction between Gal3 and T-cell immunoglobulin and mucin domain-containing-3 (TIM-3), which causes inhibition of immune responses such as T cell activation and can enable cancer cells to evade immune clearance. The phenomenon and methods of inhibiting this are explored in WO 2019 / 023247, which is expressly incorporated herein by reference in its entirety. Anti-Gal3 antibodies and methods of using them have also been explored, for example, in PCT publication WO 2020 / 160156, which is expressly incorporated herein by reference in its entirety.

[0137] There is an ongoing need for a deeper understanding of whether Gal3 plays a role in disease. Some diseases that may be associated with Gal3 include cancer, fibrosis, inflammatory diseases, neurological diseases, and primary diseases such as Alzheimer's disease. There is also a need to develop new and improved treatments for these diseases.

[0138] Disclosed herein are various embodiments of anti-Gal3 antibodies or binding fragments thereof and methods of use (eg, for the treatment of diseases provided above or elsewhere herein).

[0139] Disclosed herein are antibodies or binding fragments thereof that bind to or selectively target Gal3 and compositions thereof. Also disclosed herein are methods of using anti-Gal3 antibodies or binding fragments thereof to disrupt the interaction between Gal3 and cell surface markers and / or proteins associated with, for example, fibrosis, liver fibrosis, kidney fibrosis, cardiac fibrosis, lung fibrosis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, sepsis, atopic dermatitis, psoriasis, cancer, brain cancer, breast cancer, colorectal cancer, kidney cancer, liver cancer, lung cancer, pancreatic cancer, bladder cancer, gastric cancer, hematological malignancies, neurodegenerative diseases, and / or primary diseases (such as those caused by misfolding or aggregation of proteins in a subject).

[0140] In some embodiments, the method relates to an antibody that binds to Gal3 and disrupts the interaction between Gal3 and another protein. This can be a direct obstruction of the interaction region between Gal3 and the other protein, or an indirect change, such as binding that causes a conformational change in Gal3 so that it no longer binds to or is active against the other protein. It can also be caused by binding to a first portion of Gal3, where some other portion of the antibody obstructs or alters the interaction between Gal3 and the other protein. In some embodiments, the first portion of Gal3 is the N-terminal domain of Gal3, the tandem repeat domain (TRD) of Gal3, or the C-terminal domain of Gal3. In some embodiments, the antibody that binds to Gal3 does not bind to the C-terminal domain of Gal3. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any arrangement of any anti-Gal3 antibody or binding fragment, can be replaced with an antigen binding molecule that binds to Gal3.

[0141] Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common type of dementia. Amyloid beta (Aβ) is the main component of amyloid plaques and is therefore suspected to be a causative factor of AD. Proteolytic cleavage of amyloid precursor protein (APP, including isoforms such as APP695) produces Aβ peptide, the aggregation of which is associated with the development of Alzheimer's disease. The serum level of Gal3 in AD patients increases with the severity of memory loss. Gal3 is specifically expressed in microglia associated with Aβ plaques. Gal3 expression is also significantly increased in the frontal lobe of AD patients, and Aβ oligomerization is enhanced. Aβ peptide in human cerebrospinal fluid can undergo O-glycosylation at Tyr-10 and is elevated in AD patients.

[0142] Disclosed herein are antibodies and binding fragments specific for Gal3 and methods of use thereof for treating or preventing neurodegenerative diseases and / or primary diseases (e.g., Alzheimer's disease). The anti-Gal3 antibodies and binding fragments disclosed herein disrupt the interaction between Gal3 and proteins associated with neurodegenerative diseases and / or primary diseases. In some embodiments, the protein associated with a neurodegenerative disease and / or primary disease causes the disease due to misfolding or aggregation of the protein in the subject. A non-limiting example of a protein associated with a neurodegenerative disease and / or primary disease is amyloid beta (Aβ) peptide.

[0143] In some embodiments, the anti-Gal3 antibodies or binding fragments disclosed herein disrupt the interaction between Gal3 and APP695. Some exemplary antibodies that strongly disrupt (e.g., at least 90%) the interaction between Gal3 and APP695 include, but are not limited to, 19B5.2E6, 7D8.2D8, F846C.1B2, F846C.1H12, F846TC.14A2, F849C.8D10, F849C.8H3, 4A11.H3L1 [IMT006-5(TB00 6)], 15F10.2D6, F846TC.16B5, 23H9.2E4, F846C.1F5, IMT001-4[TB001], F846C.2H3, 14H10.2C9, 15FG7.2A7, 20H5.A3, F846TC.14E4, 3B11.2G2, 20D11.2C6, and 2D10.2B2. Some exemplary antibodies that moderately disrupt (e.g., at least 45%) the interaction between Gal3 and APP695 include, but are not limited to, 13G4.2F8, F846TC.7F10, F847C.12F12, and F847C.4B10. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any arrangement of any anti-Gal3 antibody or binding fragment, can be replaced with an antigen binding molecule that binds to Gal3.

[0144] In some embodiments, the anti-Gal3 antibodies or binding fragments disclosed herein disrupt the interaction between Gal3 and Aβ (e.g., Aβ monomers, oligomers, or fibrils, or any combination thereof). Some exemplary antibodies that strongly disrupt (e.g., at least 90%) the interaction between Gal3 and Aβ monomers include, but are not limited to, 2D10.2B2, 20D11.2C6, 3B11.2G2, 20H5.A3, 846TC.14E4, 15G7.2A7, 14H10.2C9, 846C.2H3, TB001, 846C.1F5, 846TC.16B5, TB006, 846C.1B2, 846TC.14A2, 849C.8D10, and 19B5.2E6. Some exemplary antibodies that strongly disrupt (e.g., at least 90%) the interaction between Gal3 and Aβ oligomers include, but are not limited to, 2D10.2B2, 20D11.2C6, 3B11.2G2, 20H5.A3, 846TC.14E4, 14H10.2C9, TB001, 846C.1F5, and TB006. In some embodiments, the anti-Gal3 antibodies or binding fragments disclosed herein block the interaction between Gal3 and Aβ oligomers better than the small molecule Gal3 inhibitor TD139. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any arrangement of any anti-Gal3 antibody or binding fragment, can be replaced with an antigen-binding molecule that binds to Gal3.

[0145] In some embodiments, administration of any of the anti-Gal3 antibodies or binding fragments disclosed herein can enhance cognitive function in a subject and / or reduce accumulation of toxic conformational species of Aβ, such as Aβ oligomers and / or Aβ fibrils, in the subject (if not both).

[0146] In some embodiments, administration of any of the anti-Gal3 antibodies or binding fragments disclosed herein can reduce inflammation (eg, of the brain) and / or encephalitis in a subject.

[0147] In some embodiments, administration of any of the anti-Gal3 antibodies or binding fragments disclosed herein can achieve one or more of reducing phosphorylated Tau levels in a subject, reducing microglial activation in a subject (as detected by Iba-1 antibody), or reducing Gal3 levels in the brain of a subject.

[0148] In some embodiments, administration of any of the anti-Gal3 antibodies or binding fragments disclosed herein can achieve at least one (if not both) of regenerating neuronal structure and / or reducing extracellular A[beta] in a subject.

[0149] In some embodiments, administration of any of the anti-Gal3 antibodies or binding fragments disclosed herein can promote phagocytic function of microglia in a subject and promote clearance of Aβ deposits in the subject.

[0150] In some embodiments, administration of any one of the anti-Gal3 antibodies or binding fragments disclosed herein inhibits Aβ aggregate (eg, Aβ oligomers or Aβ fibrils)-mediated microglial activation in a subject.

[0151] In some embodiments, administration of any one of the anti-Gal3 antibodies or binding fragments disclosed herein blocks the interaction between Gal3 and TLR4 or TREM2, or both.

[0152] Also provided herein are embodiments of methods for disrupting the interaction between Gal3 and cell surface markers such as TGF-β, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR, FGFR1α-IIIb, FGFR1α-IIIc, FGFR IIIc, or FGFR4. In some embodiments, the disruption can be used to alter biological processes regulated by these cell surface markers. In some embodiments, the cell surface marker is a tumor cell surface marker, a cancer cell surface marker, or a fibrosis cell surface marker.

[0153] Cells utilize a wide range of signaling molecules and cognate cell surface receptors for signaling and cellular communication. Abnormal function of these interactions has been implicated in many diseases and disorders. For example, TGF-β is a potent signaling molecule with pleiotropic effects, including regulating immune processes during the progression of cancer or fibrosis (e.g., liver fibrosis).

[0154] As an example, biological processes regulated by TGF-β include (but are not necessarily limited to): a) TGF-β regulates many biological responses, including tissue fibrosis (liver, kidney, lung, heart, etc.), cell proliferation, apoptosis, differentiation, autophagy, and immune responses; b) TGF-β plays an important role in liver physiology and pathology and contributes to all stages of disease progression: from liver injury to inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma; c) TGF-β also mediates the epithelial-mesenchymal transition process in hepatocytes, which may directly or indirectly increase the myofibroblast (MFB) population; hepatic stellate cell (HSC) activation is one of the most important steps during liver fibrosis; d) TGF-β plays an important role in the activation of HSC into MFB (MFB is the main source of extracellular matrix protein accumulation and the main regulator of fibrosis). Therefore, in some embodiments, any one or more of the above processes can be disrupted by using Gal3 antibodies that reduce the binding between Gal3 and TGF-β receptors.

[0155] TGF-β binds to the TGF-βRII receptor, which binds to and phosphorylates TGF-βRI, triggering receptor-regulated SMAD proteins (R-SMAD) SMAD2 and SMAD3 to recruit to the cytoplasmic domain of activated TGF-βRI, which then phosphorylates SMAD2 / 3. Once phosphorylated, SMAD2 / 3 forms a trimer with SMAD4, which then moves to the nucleus, where it binds to the SMAD binding element to regulate gene expression. In some embodiments, the antibodies or binding fragments provided herein change how TGF-β binds to the receptor to change TGF-β binding to TGF-βRII. In some embodiments, the antibodies or binding fragments do not change how TGF-β binds to Gal3 by changing TGF-β binding to TGF-βRII.

[0156] TGF-β activates numerous SMAD-independent signaling pathways, known as non-canonical TGF-β pathways, such as the WNT, ERK, P38, MAPK, PI3K, and AKT pathways. In some embodiments, the antibodies or binding fragments provided herein can alter how TGF-β activates these numerous SMAD-independent signaling pathways by altering how TGF-β binds to its receptor.

[0157] Inflammation plays a key role in the development of liver fibrosis. After injury occurs, infiltrating immune cells (macrophages, lymphocytes, eosinophils and plasma cells) are recruited to the damaged site. Lymphocytes produce secreted protein signaling molecules called cytokines and chemokines that activate macrophages. Activated macrophages stimulate inflammatory cells such as lymphocytes, helping to maintain a pro-inflammatory environment. During fibrosis, macrophages produce pro-fibrotic factors such as TGF-β and platelet-derived growth factor (PDGF), which control extracellular matrix turnover by regulating the balance of various matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). They are found to be very close to collagen-producing myofibroblasts, indicating that macrophages are highly correlated with the activation of MFB. In this sense, hepatic macrophages have been described as potential targets for the treatment of liver fibrosis. In vitro and in vivo studies have described that both Kupffer cells and monocyte-derived macrophages can activate HSCs through paracrine mechanisms (including through TGF-β) and induce their transdifferentiation. Resident liver macrophages secrete the chemokine CCL2 (a potent chemical attractant) to recruit monocytes that can enhance and promote fibrosis. Macrophages are important players in regulating liver fibrosis and are an important source of TGF-β. Recent observations have shown the role of TGF-β in promoting polarization of M2-like macrophages through SNAIL-induced fibrosis. M2-activation / polarization plays a relevant role in the development of fibrosis in mice and patients with liver fibrosis. Therefore, in some embodiments, the effect of TGF-β is altered by applying one or more anti-Gal3 antibodies or binding fragments thereof provided herein (which disrupt the interaction between Gal3 and TGF-β receptors), thereby changing one or more pathways or processes described above.

[0158] In some embodiments, the method involves an antibody or binding fragment thereof that binds to Gal3 and disrupts the interaction between Gal3 and a cell surface marker or cell surface receptor. In some embodiments, the cell surface marker or cell surface receptor is a cell surface marker or cell surface receptor that appears on tumor cells, immune cells, cancer cells, or fibrotic cells. This can be a direct obstruction of the interaction region between Gal3 and the cell surface marker or cell surface receptor, or an indirect change, such as binding that causes a conformational change in Gal3 so that it no longer binds to the cell surface marker or cell surface receptor or is active against the cell surface marker or cell surface receptor. It can also be caused by binding to a first portion of Gal3, wherein some other portion of the antibody obstructs or changes the interaction between Gal3 and the cell surface marker or cell surface receptor.

[0159] In some embodiments, the methods involve antibodies that bind to Gal3 and disrupt the interaction between Gal3 and TGF-β receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3 IIIc, or FGFR4, or any combination thereof. This can be a direct blockage of the interaction region between Gal3 and the TGF-β receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3 IIIc or FGFR4, or any combination thereof; or an indirect alteration, such as binding that results in a conformational change in Gal3 so that it no longer binds to the TGF-β receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3 IIIc or FGFR4, or any combination thereof; sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3IIIc or FGFR4, or any combination thereof, or is active against TGF-β receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3IIIc or FGFR4, or any combination thereof. It can also be caused by binding to a first portion of Gal3, where some other portion of the antibody blocks or alters the interaction of Gal3 with a TGF-β receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3IIIc or FGFR4, or any combination thereof.

[0160] In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any arrangement of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen-binding molecule that binds to Gal3. Therefore, whenever this disclosure refers to an antibody or binding fragment thereof, it also contemplates an antigen-binding molecule, but for simplicity, this disclosure will sometimes refer only to an antibody or binding fragment thereof. It should be noted that the term "antigen-binding molecule" encompasses antibodies and binding fragments thereof and represents a broader class of selection.

[0161] The present disclosure claims priority to one or more priority documents, which have been submitted in one or more appendices. All subject matter disclosed in the priority document and any appendix is ​​hereby expressly considered as a part of the disclosure of this document, as a further embodiment that can be combined and / or modified with any embodiment provided herein. All subject matter disclosed in the priority document and the appendix, including but not limited to antibodies, their binding fragments, antigen binding molecules and any methods such as preparation methods, methods of use or methods of treatment, can be applied to any embodiment or arrangement disclosed in this section of the application. Similarly, all subject matter disclosed herein, including but not limited to antibodies, their binding fragments, antigen binding molecules and any methods such as preparation methods, methods of use or methods of treatment, are considered to be applied to any embodiment or arrangement disclosed in the priority document and the appendix. definition

[0162] In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols generally indicate similar components unless the context indicates otherwise. The illustrative embodiments described in the detailed description, the accompanying drawings, and the claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It is readily understood that aspects of the present disclosure, as generally described herein and illustrated in the accompanying drawings, may be arranged, substituted, combined, separated, and designed in a variety of different configurations, all of which are expressly contemplated herein.

[0163] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one skilled in the art to which the claimed subject matter belongs. It should be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of any subject matter claimed.

[0164] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0165] As used herein, the articles "a / an" and "a / an" refer to one or more than one (e.g., at least one) of the grammatical object of the article. For example, "an element" means one or more than one element.

[0166] "About" means a mass, level, value, quantity, frequency, percentage, dimension, size, amount, weight, or length that varies by as much as 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1%.

[0167] Throughout this specification, unless the context requires otherwise, the words "comprises," "comprising," and "containing" will be understood to imply the inclusion of the stated steps or elements or groups of steps or elements, but not the exclusion of any other steps or elements or groups of steps or elements. "Consisting of" means including and limited to whatever follows the phrase "consisting of." Thus, the phrase "consisting of" indicates that the listed elements are required or mandatory, and that other elements may be absent. "Consisting essentially of" means including any elements listed with the phrase, and is limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure of the listed elements. Thus, the phrase "consisting essentially of" indicates that the listed elements are required or mandatory, but other elements are optional and may be present or absent depending on whether they substantially affect the activity or action of the listed elements.

[0168] As used herein, the terms "individual," "subject," and "patient" mean any mammal. In some embodiments, the mammal is a human. In some embodiments, the mammal is non-human. None of these terms require or are limited to conditions characterized by supervision (e.g., continuous or intermittent) by a health care worker (e.g., a physician, registered nurse, licensed practical nurse, physician assistant, paramedic, or hospice worker).

[0169] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear, cyclic, or branched, it may include modified amino acids, and it may be interrupted by non-amino acids. The term also encompasses amino acid polymers that have been modified, for example, by sulfation, glycosylation, lipidation, acetylation, phosphorylation, iodination, methylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, transfer-RNA-mediated addition of amino acids to a protein, such as arginylation, ubiquitination, or any other manipulation, such as conjugation with a labeling component.

[0170] As used herein, the term "amino acid" refers to natural and / or unnatural or synthetic amino acids, including glycine and both the D or L optical isomers, as well as amino acid analogs and peptidomimetics.

[0171] A polypeptide or amino acid sequence "derived from" a specified protein refers to the source of the polypeptide. Preferably, the polypeptide has an amino acid sequence substantially identical to the amino acid sequence of the polypeptide encoded in the sequence, or a portion thereof, wherein the portion consists of at least 10-20 amino acids, or at least 20-30 amino acids, or at least 30-50 amino acids, or is immunologically identifiable with the polypeptide encoded in the sequence. The term also includes polypeptides expressed from a specified nucleic acid sequence. Peptide sequences having at least 80%, 85%, 90%, 95%, 99% or 100% homology to any of the peptide sequences disclosed herein and having the same or similar functional properties are contemplated. The percentage of homology can be determined based on amino acid substitutions, deletions or additions between the two peptide sequences. Peptide sequences having a certain percentage of homology to any of the peptide sequences disclosed herein can be generated and tested by those skilled in the art by conventional methods.

[0172] As used herein, the term "antibody" means what one skilled in the art would recognize it to mean, and further, it is intended to include any polypeptide chain-containing molecular structure having a specific shape that is suitable for and recognizes an epitope, wherein one or more non-covalent binding interactions stabilize the complex between the molecular structure and the epitope. The antibodies used in the present invention can be polyclonal antibodies, although monoclonal antibodies are preferred because they can be replicated by cell culture or recombination and can be modified to reduce their antigenicity.

[0173] In addition to complete immunoglobulins (or their recombinant counterparts), immunoglobulin fragments or "binding fragments" (e.g., Fab', F(ab')2, single-chain variable fragments (scFv), diabodies, miniantibodies, nanobodies, single-domain antibodies (sdAb) or other fragments) comprising epitope binding sites can be used as antibody moieties in the present invention. Such antibody fragments can be produced from whole immunoglobulins by cleavage with ricin, pepsin, papain or other proteases. Minimal immunoglobulins can be designed using recombinant immunoglobulin technology. For example, "Fv" immunoglobulins for use in the present invention can be produced by connecting the variable light chain region to the variable heavy chain region via a peptide connector (e.g., polyglycine or another sequence that does not form an alpha helix or beta sheet motif). Nanobodies or single-domain antibodies can also be derived from alternative organisms, such as dromedaries, camels, llamas, alpacas or sharks. In some embodiments, the antibody can be a conjugate, such as a pegylated antibody, a drug, a radioisotope or a toxin conjugate. Monoclonal antibodies directed against a specific epitope or combination of epitopes will allow targeting and / or depletion of cell populations expressing the marker. Monoclonal antibodies can be used to screen for cell populations expressing the marker using a variety of techniques, and include magnetic separation using antibody-coated magnetic beads, "panning" using antibodies attached to a solid matrix (i.e., a plate), and flow cytometry (e.g., U.S. Patent No. 5,985,660, expressly incorporated herein by reference in its entirety).

[0174] As is known in the art, the term "Fc region" is used to define the C-terminal region of an immunoglobulin heavy chain. An "Fc region" can be a native sequence Fc region or a variant Fc region. Although the boundaries of an immunoglobulin heavy chain Fc region may vary, the human IgG heavy chain Fc region is generally defined as extending from the amino acid residue at position Cys226 or from Pro230 to its carboxyl terminus. The numbering of residues in the Fc region is the EU index numbering 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 generally comprises two constant domains, CH2 and CH3. As is known in the art, the Fc region can exist as a dimer or a monomer.

[0175] 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, alone or in combination.

[0176] The "variable region" of an antibody refers to an antibody light chain variable region or an antibody heavy chain variable region, either alone or in combination. As known in the art, the variable regions of heavy and light chains are each composed of four framework regions (FRs) connected by three complementary determining regions (CDRs) also referred to as hypervariable regions, and contribute to the formation of the antigen binding site of the antibody. If a variant of a subject's variable region is desired, particularly with a replacement in the amino acid residues outside the CDR region (i.e., in the framework region), suitable amino acid replacements can be identified by comparing the subject's variable region with the variable region of other antibodies containing CDR1 and CDR2 sequences in the same canonical category as the subject's variable region, preferably conservative amino acid replacements (Chothia and Lesk, J Mol Biol 196 (4): 901-917, 1987).

[0177] In certain embodiments, the clear description of CDR and the identification of residues including antibody binding sites are completed by parsing the structure of the antibody and / or parsing the structure of the antibody-ligand complex. In certain embodiments, this can be completed by any of various techniques known to those skilled in the art, such as X-ray crystallography. In certain embodiments, various analytical methods can be used to identify or simulate (approximate) CDR regions. In certain embodiments, various analytical methods can be used to identify or simulate CDR regions. Examples of such methods include but are not limited to Kabat definition, Chothia definition, IMGT method (Lefranc et al., 2003) Dev Comp Immunol. 27: 55-77), computing programs such as Paratome (Kunik et al., 2012, Nucl Acids Res. W521-4), AbM definition and conformational definition.

[0178] The Kabat definition is a standard for numbering residues in antibodies and is commonly 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 the Chothia definition takes into account the position of certain structural loop regions. See, e.g., Chothia et al., 1986, J. Mol. Biol., 196:901-17; Chothia et al., 1989, Nature, 342:877-83. The AbM definition uses an integrated set of computer programs produced by the Oxford Molecular Group that model antibody structures. 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. AbM definitions use a combination of knowledge databases and ab initio methods to model the tertiary structure of an antibody from the primary sequence, such as those described by Samudrala et al., 1999, "Ab Initio Protein Structure Prediction Using a Combined Hierarchical Approach", PROTEINS, Structure, Function and Genetics Suppl., 3:194-198. Contact definitions are based on analysis of available complex crystal structures. See, for example, MacCallum et al., 1996, J. Mol. Biol., 5:732-45. In another approach, referred to herein as "conformational definition" of the CDRs, the positions of the CDRs can be identified as residues that make enthalpic contributions to antigen binding. See, for example, Makabe et al., 2008, Journal of Biological Chemistry, 283:1156-1166. Still other CDR boundary definitions may not strictly follow one of the above methods, but will still overlap with at least a portion of the Kabat CDRs, although they may be shortened or lengthened based on predictions or experimental findings that particular residues or groups of residues do not significantly affect antigen binding. As used herein, a CDR can refer to a CDR defined by any method known in the art, including a combination of methods. The methods used herein can utilize CDRs defined according to any of these methods.For any given embodiment containing more than one CDR, the CDRs can be defined according to any of the Kabat, Chothia, extended, IMGT, Paratome, AbM and / or conformational definitions, or any combination of the foregoing.

[0179] As used herein, the term "competition" about an antibody means the first antibody or its antigen-binding portion thereof, in a sufficiently similar manner to the second antibody or its antigen-binding portion thereof, so that the binding results of the first antibody and its cognate epitope can be detectably reduced when the second antibody is present, compared to the binding of the first antibody in the absence of the second antibody. The alternative scheme in which the binding of the second antibody and its epitope can also be detectably reduced in the presence of the first antibody is possible but not necessarily the case. That is, the first antibody can suppress the binding of the second antibody and its epitope, while the second antibody does not suppress the binding of the first antibody and its corresponding epitope. However, each antibody can detectably suppress the binding of another antibody and its cognate epitope or ligand, whether in the same, greater or lesser degree, antibodies are referred to as each other "cross competition", for binding their respective epitopes. The present invention encompasses competition and cross-competition antibodies. Regardless of the mechanism (e.g., steric hindrance, conformational change or being bound to a common epitope or its portion) of such competition or cross-competition, based on the teachings provided herein, it will be appreciated that such competition and cross-competition antibodies are encompassed and can be used for methods disclosed herein.

[0180] "Preferentially binding" or "specifically binding" (used interchangeably herein) to an antibody of an epitope are terms well understood in the art, and methods of determining such specific or preferential binding are also well known in the art. A molecule is said to exhibit "specific binding" or "preferentially binding" if it reacts or binds to a particular cell or substance more frequently and / or more rapidly, and / or with a longer duration and / or greater affinity than the molecule reacts to or binds to an alternative cell or substance. An antibody "specifically binds" or "preferentially binds" to a target if the antibody binds with greater affinity and / or avidity, and / or more readily, and / or with a longer duration than the antibody binds to other substances. For example, an antibody that specifically or preferentially binds to a CFD epitope is an antibody that binds to the epitope with greater affinity and / or avidity, and / or more readily, and / or with a longer duration than the antibody binds to other CFD epitopes or non-CFD epitopes. It is also understood by reading this definition that, for example, an antibody (or portion 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. Typically, but not necessarily, reference to binding means preferential binding.

[0181] As used herein, the term "antigen binding molecule" refers to a molecule comprising an antigen binding portion that is bound to an antigen, and optionally comprising a scaffold or framework portion that allows the antigen binding portion to adopt a conformation that promotes the binding of the antigen binding portion or provides some other properties for 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 is bound to an antigen. In some embodiments, the antigen binding portion comprises all three CDRs from an antibody heavy chain that is bound to an antigen or from an antibody light chain that is bound to an 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 is bound to an antigen. In some embodiments, the antigen binding portion is an antibody fragment.

[0182] The non-limiting examples of antigen binding molecules include antibodies, antibody fragments (for example, antigen binding fragments of antibodies), antibody derivatives and antibody analogs. Other specific examples include, but are not limited to, single-chain variable fragments (scFv), nano antibodies (for example, the VH domains of camel 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 complementary determining region (CDR) fragments. These molecules can be derived from any mammalian source, such as humans, mice, rats, rabbits, pigs, dogs, cats, horses, donkeys, guinea pigs, goats or camels. Antibody fragments can compete with intact antibodies for binding to target antigens, and fragments can be produced by modification (for example, enzymatic or chemical cleavage) of intact antibodies or synthesized de novo using recombinant DNA technology or peptide synthesis. Antigen binding molecules can include, for example, alternative protein scaffolds or artificial scaffolds with transplanted CDRs or CDR derivatives. Such scaffolds include, but are not limited to, antibody-derived scaffolds comprising mutations introduced to, for example, stabilize the three-dimensional structure of the antigen-binding molecule, and fully synthetic scaffolds comprising, for example, biocompatible polymers. See, for example, Korndorfer et al., 2003, Proteins: Structure, Function and Bioinformatics, Vol. 53, Publication 1: 121-129 (2003); Roque et al., Biotechnol. Prog. 20: 639-654 (2004). In addition, peptide antibody mimics ("PAMs") can be used, as well as scaffolds based on antibody mimics utilizing fibronectin components as scaffolds.

[0183] Antigen binding molecules can also include proteins comprising one or more antibody fragments, which are incorporated into a single polypeptide chain or multiple polypeptide chains. For example, antigen binding molecules can include but are not limited to diabodies (see, for example, EP 404,097; WO 93 / 11161 and Hollinger et al., Proc. Natl. Acad. Sci. USA, Vol. 90: 6444-6448, 1993); intracellular antibodies; domain antibodies (single VL or VH domains or two or more VH domains connected by a peptide connector; see Ward et al., Nature, Vol. 341: 544-546, 1989); large antibodies (maxibodies) (fused to 2 scFvs in Fc region, see Fredericks et al., Protein Engineering, Design & Selection, Vol. 17: 95-106, 2004 and Powers et al., Journal of Immunological Methods, Vol. 251: 123-135, 2001); triabody; tetrabody; minibody (scFv fused to the CH3 domain; see Olafsen et al., Protein Eng Des Sel., Vol. 17: 315-23, 2004); peptibody (one or more peptides attached to the Fc region, see WO 00 / 24782); linear antibody (a pair of tandem Fd fragments (VH-CH1-VH-CH1) that together with complementary light chain polypeptides 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 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).

[0184] In certain embodiments, the antigen binding molecules may have a structure such as an immunoglobulin. An "immunoglobulin" is a tetrameric molecule, each tetramer comprising two pairs of identical polypeptide chains, each pair having a "light" chain (about 25 kDa) and a "heavy" chain (about 50-70 kDa). The amino terminal portion of each chain includes a variable region of about 100 to 110 or more amino acids that is primarily responsible for antigen recognition. The carboxyl terminal portion of each chain defines a constant region that is primarily responsible for effector function.

[0185] As used herein, the term "treatment" (and as well understood in the art) means a method for obtaining a beneficial or desired result, including a clinical result, in a subject's condition. Beneficial or desired clinical results may include, but are not limited to, alleviating or improving one or more symptoms or conditions, alleviating the extent of the disease, stabilizing (i.e., not worsening) the disease state, preventing the transmission or spread of the disease, delaying or slowing the progression of the disease, improving or alleviating the disease state, alleviating disease relapse and remission, whether partial or complete, whether detectable or undetectable. As used herein, "treatment" also includes prophylactic treatment. Treatment methods include administering a therapeutically effective amount of an active agent to the subject. The administration step may consist of a single administration or may include a series of administrations. The composition is administered to the subject in an amount and duration sufficient to treat the subject. The length of the treatment cycle depends on a variety of factors, such as the severity of the condition, the age and genetic characteristics of the subject, the concentration of the active agent, the activity of the composition used in the treatment, or a combination thereof. It should also be understood that the effective dose of the agent used for treatment or prevention can increase or decrease over the course of a specific treatment or prevention regimen. Changes in dosage can result and become apparent through standard diagnostic assays known in the art. In some cases, long-term administration may be required.

[0186] As used herein, the terms "effective amount" or "effective dose" have their simple and common meaning as understood in the specification, and refer to the amount of the composition or compound that results in an observable specified effect. The actual dosage level of the active ingredient in the active composition of the presently disclosed subject matter can be varied to administer an amount of the active composition or compound that effectively achieves a specified response for a specific subject and / or application. The selected dosage level can vary based on a variety of factors, including but not limited to the activity of the composition, formulation, route of administration, combination with other drugs or treatments, severity of the condition being treated, and physical condition and past medical history of the subject being treated. In some embodiments, a minimum dose is administered, and the dose is gradually increased to the minimum effective amount in the absence of dose-limiting toxicity. Determination and adjustment of the effective dose, as well as assessment of when and how to make such adjustments, are contemplated herein.

[0187] The term "administering" includes oral administration, topical contact, administration as a suppository, intravenous, intraperitoneal, intramuscular, intralesional, intrathecal, intranasal or subcutaneous administration, or implantation of a sustained-release device, such as a micro-osmotic pump to a subject. By any approach, including parenteral and transmucosal (e.g., buccal, sublingual, palate, gums, nose, vagina, rectal or transdermal) administration. Parenteral administration includes, for example, intravenous, intramuscular, intraarteriolar, intradermal, subcutaneous, intraperitoneal, intraventricular and intracranial. Other modes of delivery include, but are not limited to, the use of liposome formulations, intravenous infusion, transdermal patches, etc. By "co-administering" means administering the second compound as herein described, just before or just after the first compound as herein described.

[0188] As used herein, the term "therapeutic target" refers to a gene or gene product that, upon modulation of its activity, can provide modulation of a disease phenotype (e.g., by modulating expression, biological activity, etc.). As used throughout, "modulate" means an increase or decrease in the indicated phenomenon (e.g., modulation of a biological activity refers to an increase in biological activity or a decrease in biological activity).

[0189] As used herein, the terms "standard of care", "best practices" and "standard therapy" refer to treatments that are accepted by medical practitioners as suitable, appropriate, effective and / or widely used treatments for certain diseases. The standard of care for certain diseases depends on many different factors, including the biological effects of the treatment, area or location in the body, patient status (such as age, weight, sex, genetic risk, other disabilities, 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 effectiveness in clinical trials that set standards by regulatory agencies such as the U.S. Food and Drug Administration, the International Committee for Harmonization, Health Canada, the European Medicines Agency, the Therapeutic Goods Administration, the Central Drug Standard Control Agency, the State Drug Administration, the Drug and Medical Device Administration, the Ministry of Food and Drug Safety and the World Health Organization. The standard of care for a disease may include, but is not limited to, surgery, radiation, chemotherapy, targeted therapy or immunotherapy (such as PD1 / PDL1 or CTLA4 blocking therapy). For example, temozolomide is an oral chemotherapy compound used as a standard of care treatment for brain cancers such as glioblastoma and astrocytoma. One skilled in the art will appreciate that the ability of temozolomide to cross the blood-brain barrier is one aspect that determines its utility as a standard of care for these diseases, and that temozolomide may not necessarily be used as a standard of care treatment for other diseases as well.

[0190] As used herein, the term "supplement" refers to a compound, molecule or substance that is provided together with at least one other compound, molecule or substance to treat cancer and that has an effect on the patient. The term "immuno-oncology supplement" refers to a supplement that has an effect on the patient's immune system. The administration of at least two compounds, molecules or substances may also be referred to as combination therapy. In some embodiments, at least one other compound, molecule or substance is PD1 blocking therapy, PDL1 blocking therapy or CTLA4 blocking therapy.

[0191] As used herein, "PD1 blocking therapy" refers to a PD1 inhibitor therapy involving blocking the interaction between programmed cell death protein 1 (PD1) and programmed death-ligand 1 (PDL1). Cancer cells express PDL1, which binds to PD1 expressed on T cells or other immune cells to inhibit the immune clearance of cancer cells. PD1 inhibitors block this interaction by binding to or inhibiting PD1. PD1 inhibitors include but are not limited to pembrolizumab, nivolumab, cemiplizumab, spartalizumab, carrelizumab, sintilimab, tislelizumab, toripalizumab, AMP-224 or AMP-514 or any combination thereof. As used herein, "PDL1 blocking therapy" refers to a PDL1 inhibitor therapy with a similar effect to a PD1 inhibitor. PDL1 inhibitors bind to or inhibit PDL1. PDL1 inhibitors include but are not limited to atezolizumab, avelumab, durvalumab, KN035, CK-301, AUNP12, CA-170 or BMS-986189 or any combination thereof." PD1 / PDL1 blocking therapy" refers to PD1 blocking therapy, PDL1 blocking therapy or both. As used herein, "CTLA4 blocking therapy" refers to a CTLA4 inhibitor therapy involving blocking the interaction between cytotoxic T lymphocyte-associated protein 4 (CTLA4) and CD80 or CD86. T cells express CTLA4, which binds to CD80 or CD86 on other T cells to suppress their immune activity. CTLA4 inhibitors include but are not limited to ipilimumab or tremelimumab. PD1 blocking therapy, PDL1 blocking therapy and / or CTLA4 blocking therapy are used as standard of care treatments for some cancers or other diseases.

[0192] As used herein, the term "neurological disorder" refers to a disease affecting the central and / or peripheral nervous system of a patient. Neurological disorders have physical causes, such as external or internal mechanical damage (such as stroke or concussion), biological damage (such as infection), chemical damage (such as toxins or drugs), aging and age-related aging, genetics and many other causes. Some neurological disorders are caused by the influence or accumulation of mutated or misfolded proteins. These diseases may involve the death of neurons or other cell types associated with the nervous system. Non-limiting examples of neurological disorders include inflammation, encephalitis, Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, olfactory dysfunction, aphasia, Bell's palsy, transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease, fatal familial insomnia, epilepsy, spasticity, neurodevelopmental, Tourette syndrome, neuroinfectious diseases, meningitis, encephalitis, mad cow disease, West Nile virus encephalitis, neuro-AIDS, fragile X syndrome, Guillain-Barré syndrome, brain metastasis or brain cancer or other diseases known to those skilled in the art. Some neurological disorders can also be classified as primary diseases.

[0193] As used herein, the term "primary disease" refers to a disease caused by the abnormal folding or accumulation of a protein. Abnormal proteins can acquire toxic functions or lose their normal functions. Misfolded proteins can induce the misfolding of proteins that are normally folded in other ways, and it is possible to produce the expansion of the disease (such as prion disease). Some non-restrictive examples of primary diseases include Alzheimer's disease, cerebral beta-amyloid angiopathy, glaucoma, retinal ganglion cell degeneration, Parkinson's disease, Lewy dementia, multiple system atrophy, synucleinopathy, Pick's disease, cortical basal degeneration, tau disease, frontotemporal lobar degeneration, Huntington's disease, dentate nucleus, rubral nucleus, globus pallidus, Lewy body atrophy, spinal bulbar muscular atrophy, spinocerebellar ataxia, fragile X syndrome, Baratela-Scott syndrome, Friedrich's ataxia, myotonic dystrophy, Alexander disease, familial British dementia, familial Danish dementia, Pelvic Illness, seipin disease , AA (secondary) amyloidosis, type II diabetes, fibrinogen amyloidosis, dialysis amyloidosis, inclusion body myositis / myopathy, familial amyloidotic neuropathy, senile systemic amyloidosis, serpinopathy, cardiac atrial amyloidosis, pituitary prolactinoma, insulin amyloidosis, corneal lactoferrin amyloidosis, pulmonary alveolar proteinosis, seminal vesicle amyloidosis, cutaneous lichen amyloidosis, Mallory bodies or odontogenic (Pindborg) tumor amyloid, or any disease caused by misfolding or aggregation of proteins or other diseases known to those skilled in the art.

[0194] As used herein, unless otherwise specifically indicated, the terms "amyloid-beta", "amyloid-β" and "Aβ" have their ordinary and common meanings as understood in accordance with the specification, and refer to amyloid beta protein or peptide, amyloid beta precursor protein or peptide, intermediates, and modifications and fragments thereof. In particular, "Aβ" refers to any peptide produced by proteolytic processing of the amyloid precursor protein (APP) gene product, especially peptides associated with amyloid pathology.

[0195] As used herein, the term "blood-brain barrier" has its general and common meaning as understood according to the specification, and refers to the protective cell boundary between the circulatory system and the central nervous system. This boundary includes brain capillary endothelial cells (BCEC) of closely interacting capillaries connected by tight junctions, which also show selectivity for different small and large molecules, in addition to larger particles (such as circulating immune cells and pathogenic microorganisms). Generally, small polar molecules or hydrophobic molecules can diffuse through the blood-brain barrier naturally, but larger and / or more polar molecules (such as glucose, protein) need specific transporters expressed by endothelial cells to pass through the barrier. Some antibodies have been shown to be able to pass through the blood-brain barrier by having specificity for cell receptors or transporters on endothelial cells, which are internalized and undergo transcytosis. The BBB plays a role as a physical, metabolic and immune barrier. As disclosed herein in some embodiments, the antibodies disclosed herein or their binding fragments may be able to pass through the blood-brain barrier of the subject. In some embodiments, the subject may have a complete blood-brain barrier. In some embodiments, the subject may have a damaged or dysfunctional blood-brain barrier. In some embodiments, the damaged or dysfunctional blood-brain barrier is due to a neurodegenerative disease including, but not limited to, Alzheimer's disease, or is associated with damage associated with brain cancer, such as primary and / or secondary brain tumors.

[0196] As used herein, the term "neuronal regeneration" has its general and common meaning as understood according to the specification, and refers to the new growth of cells or its components associated with the nervous system. For example, regeneration can occur together with the development of neurons, glial cells, oligodendrocytes, astrocytes, ependymal cells, microglia or its components (such as axons, dendrites, myelin) or new synapses / neurons interacting. Although the regeneration of neuronal tissue is generally much slower than other tissues of adults, some repairs do occur when damaged or injured. Although there is currently no treatment that enhances neuronal regeneration, treatment and preventive measures are being studied, for example, preventing diseases such as the neurodegeneration of Alzheimer's disease and multiple sclerosis. As disclosed herein in some embodiments, antibodies disclosed herein or their binding fragments may be able to promote neuronal regeneration.

[0197] The terms "cancer," "neoplasm," "tumor," and "cancer" are used interchangeably herein and refer to cells that exhibit relatively autonomous growth, so they exhibit an abnormal growth phenotype characterized by a significant loss of control of cell proliferation. In general, cells of interest for detection or treatment in the present application include precancerous (e.g., benign), malignant, pre-metastatic, metastatic, and non-metastatic cells. The detection of cancer cells is particularly interesting. The "normal" of the term "normal cell" used in this context refers to a cell with an untransformed phenotype or a cell that exhibits the morphology of an untransformed cell of the tissue type being examined. A "cancerous phenotype" generally refers to any of a variety of biological phenomena that are characteristic of cancer cells, which can vary with the type of cancer. A cancerous phenotype is typically identified by abnormalities in, for example, cell growth or proliferation (e.g., uncontrolled growth or proliferation), regulation of the cell cycle, cell mobility, cell-cell interactions, or metastasis.

[0198] The term "tumor microenvironment" refers to the cellular environment in which a tumor exists, including tumor cells and surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules, and extracellular matrix.

[0199] The term "immune cell" refers to a cell of hematopoietic origin that is involved in the specific recognition of an antigen. Immune cells include antigen presenting cells (APCs) such as dendritic cells or macrophages, B cells, T cells, natural killer cells, and myeloid cells such as monocytes, macrophages, eosinophils, mast cells, basophils, and granulocytes.

[0200] The term "immune response" refers to a T cell-mediated and / or B cell-mediated immune response. Exemplary immune responses include activation of B cell responses (e.g., antibody production), T cell responses (e.g., cytokine production and cytotoxicity) and cytokine responsive cells (e.g., macrophages). The term "activated immune response" refers to the level of T cell-mediated and / or B cell-mediated immune responses enhanced using methods well known to those skilled in the art. In one embodiment, the enhanced level is at least 20-50%, optionally at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 120%, at least 150% or at least 200%.

[0201] As used herein, the term "transforming growth factor beta receptor" (TGF-b receptor or TGF-β receptor) refers to a family of serine / threonine kinase receptors expressed on the cell surface that are specific for the protein transforming growth factor beta (TGF-b, TGF-β). The interaction between TGF-b and the receptor triggers a signal transduction pathway that is responsible for many functions, including but not limited to cell growth, differentiation (e.g., stem cells, immune cells), apoptosis, homeostasis, chemotaxis, inflammation, and immune cell activation. The TGF-b receptor family includes TGF-b receptor type 1 (TGFbR1), TGF-b receptor type 2 (TGFbR2), and TGF-b receptor type 3 (TGFbR3).

[0202] As used herein, the term "vascular endothelial growth factor receptor" (VEGFR) refers to a family of tyrosine kinase receptors specific for vascular endothelial growth factor (VEGF). The VEGFR family includes VEGFR1, VEGFR2, and VEGFR3.

[0203] As used herein, the term "epidermal growth factor receptor" (EGFR, ErbB1, HER1) refers to a tyrosine kinase receptor specific for epidermal growth factor (EGF) and transforming growth factor alpha (TGFα) that belongs to the ErbB family of tyrosine kinases.

[0204] As used herein, the term "platelet-derived growth factor receptor" (PDGFR) refers to a family of tyrosine kinase receptors specific for platelet-derived growth factor (PDGF). The PDGFR family includes PDGFRα (PDGFRa, PDGFRα) and PDGFRβ (PDGFRb, PDGFRβ).

[0205] As used herein, the term "HER2 / neu" (ErbB2, HER2) refers to a tyrosine kinase receptor that belongs to the ErbB family of tyrosine kinases.

[0206] As used herein, the terms "hepatocyte growth factor receptor" and "tyrosine protein kinase Met" (HGFR, cMet, c-Met) refer to the tyrosine kinase receptor specific for hepatocyte growth factor / scatter factor (HGF / SF).

[0207] As used herein, the term "tumor necrosis factor soluble receptor 1" (TNF sRI) refers to the soluble fragment of TNF-alpha after proteolytic cleavage by TNF-alpha converting enzyme.

[0208] As used herein, the term "integrin-associated protein" (CD47, IAP) refers to a transmembrane surface signaling protein that belongs to the immunoglobulin superfamily.

[0209] As used herein, the term "fibroblast growth factor receptor" (FGFR) refers to a family of tyrosine kinase receptors specific for fibroblast growth factor (FGF). The FGFR family includes FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3 IIIc, and FGFR4.

[0210] As used herein, the term "fibrosis" refers to a medical condition in which a tissue or organ becomes hard or scarred due to the unregulated production of an extracellular matrix (such as collagen). Fibrosis is associated with chronic inflammation in which immune cells (such as macrophages) signal fibroblasts to express extracellular matrix proteins in response. This signaling is achieved through growth receptor pathways including but not limited to TGF-b, EGFR, PDGFR, FGFR, VEGFR, or cMet pathways, although there are other pro-fibrotic pathways. Fibrosis includes but is not limited to liver fibrosis, bridging fibrosis, cirrhosis, renal fibrosis, pulmonary fibrosis, idiopathic pulmonary fibrosis, cystic fibrosis, cardiovascular fibrosis, arterial fibrosis, venous thrombosis, arthrofibrosis, Crohn's disease, Dupuytren's contracture, keloids, mediastinal fibrosis, myelofibrosis, Peyronie's disease, nephrogenic systemic fibrosis, progressive massive fibrosis, retroperitoneal fibrosis, or systemic sclerosis.

[0211] As used herein, the term "non-alcoholic fatty liver disease" (NAFLD) refers to fat accumulation in the liver due to causes other than alcohol use. A more severe form of NAFLD is "non-alcoholic steatohepatitis" (NASH), which is further defined as inflammation and fibrosis of the liver. NAFLD and NASH can ultimately lead to cirrhosis, liver cancer, liver failure, or cardiovascular disease.

[0212] As used herein, the term "sepsis" refers to a condition characterized by an extreme inflammatory immune response to a pathogenic infection. As used herein, the term "atopic dermatitis" (eczema) refers to an autoimmune condition characterized by inflammation of the skin, which causes redness, itching, and a rash. As used herein, the term "psoriasis" refers to an autoimmune condition characterized by inflammation of the skin, which causes redness, itching, dryness, and a rash.

[0213] The term "% w / w" or "% wt / wt" means the percentage expressed as the weight of an ingredient or agent relative to the total weight of the composition multiplied by 100. Exemplary anti-Gal3 antibodies

[0214] Unless otherwise indicated, the complementarity defining regions disclosed herein follow the IMGT definition. In some embodiments, the CDRs may be replaced by Kabat, Chothia, or other definitions accepted by those skilled in the art.

[0215] It will be understood that antibodies having antibody names described herein may be referred to using abbreviated versions of the antibody names so long as there is no conflict with another antibody described herein. For example, 2D10.2B2 may be referred to as 2D10.

[0216] In some embodiments, the anti-Gal3 antibody or its binding fragment binds to a specific epitope within the Gal3 protein. In some cases, the anti-Gal3 antibody or its binding fragment binds to a specific epitope within the Gal3 protein. Figure 16 A specific epitope within the Gal3 protein having the amino acid sequence of SEQ ID NO: 1 provided in .

[0217] In some cases, an anti-Gal3 antibody or binding fragment thereof can bind to Figure 17 At least 1, 2, 3, 4, 5, 6, 10, 15 or 20 amino acid residues within the peptide set forth in .

[0218] In some embodiments, the anti-Gal3 antibody or its binding fragment can bind to at least 1, 2, 3, 4, 5, 6, 10, 15, or 20 amino acid residues within amino acid residues 1-20 of SEQ ID NO: 1. In some embodiments, the anti-Gal3 antibody or its binding fragment can bind to at least 1, 2, 3, 4, 5, 6, 10, 15, or 20 amino acid residues within amino acid residues 31-50 of SEQ ID NO: 1. In some embodiments, the anti-Gal3 antibody or its binding fragment can bind to at least 1, 2, 3, 4, 5, 6, 10, 15, or 20 amino acid residues within amino acid residues 51-70 of SEQ ID NO: 1. In some embodiments, the anti-Gal3 antibody or its binding fragment can bind to at least 1, 2, 3, 4, 5, 6, 10, 15, or 20 amino acid residues within amino acid residues 61-80 of SEQ ID NO: 1. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0219] In some cases, the anti-Gal3 antibody or its binding fragment 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 2 (SEQ ID NO: 4), peptide 3 (SEQ ID NO: 5), peptide 4 (SEQ ID NO: 6), peptide 5 (SEQ ID NO: 7), peptide 6 (SEQ ID NO: 8), peptide 7 (SEQ ID NO: 9), peptide 8 (SEQ ID NO: 10), or peptide 17 (SEQ ID NO: 19), or any combination thereof. In some embodiments, the anti-Gal3 antibody or its binding fragment 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, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0220] Some exemplary antibodies that bind to peptide 1 (SEQ ID NO: 3) are 23H9.2E4, F846C.1H5, F846TC.14A2, F846TC.7F10, F847C.10B9, F847C.12F12, F847C.26F5, and F847C.4B10.

[0221] Some exemplary antibodies that bind to peptide 2 (SEQ ID NO: 4) are 15F10.2D6, 7D8.2D8, F846TC.14E4, F849C.8D10, and F849C.8H3.

[0222] Some exemplary antibodies that bind to peptide 3 (SEQ ID NO: 5) are 15F10.2D6, 7D8.2D8, and F849C.8D10.

[0223] Some exemplary antibodies that bind to peptide 4 (SEQ ID NO: 6) are 13A12.2E5 and 15F10.2D6.

[0224] Some exemplary antibodies that bind to peptide 5 (SEQ ID NO: 7) are F846C.1B2 and F846C.1H12.

[0225] Some exemplary antibodies that bind to peptide 6 (SEQ ID NO: 8) are 13A12.2E5, 14H10.2C9, 23H9.2E4, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H12, F846C.2H3, and F846TC.16B5.

[0226] Some exemplary antibodies that bind to peptide 7 (SEQ ID NO: 9) are 14H10.2C9, 23H9.2E4, F846C.1B2, F846TC.14A2, F847C.10B9, F847C.12F12, and F847C.26F5.

[0227] Some exemplary antibodies that bind to peptide 8 (SEQ ID NO: 10) are 23H9.2E4 and F846TC.14A2.

[0228] Some exemplary antibodies that bind to peptide 17 (SEQ ID NO: 19) are 7D8.2D8, F846C.1F5, F846C.1H12, F846TC.16B5, F847C.11B1, and F849C.8H3.

[0229] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is epitope binned. Figure 33 Epitope bins for some exemplary antibodies are depicted. An exemplary binning process is described in detail in Example 3.

[0230] In some embodiments, antibody TB001 is classified as bin 1.

[0231] In some embodiments, antibodies TB006, 19B5.2E6, 20H5.A3, 23H9.2E4, and 2D10.2B2 are classified as bin 3.

[0232] In some embodiments, antibody 20D11.2C6 is classified as bin 5.

[0233] In some embodiments, antibodies 13A12.2E5 and 3B11.2G2 are classified as bin 7.

[0234] In some embodiments, antibodies 14H10.2C9, 15F10.2D6, 7D8.2D8, F846TC.14E4, F846TC.7F10, and F849C.8D10 are classified as bin 8.

[0235] In some embodiments, antibody 12G5.D7 is classified as bin 10.

[0236] In some embodiments, antibody 846.2B11 is classified as bin 16.

[0237] In some embodiments, antibodies F846C.1B2, F846C.1F5, F846C.1H12, F846C.2H3, and F846TC.16B5 are classified as bin 17.

[0238] In some embodiments, antibody 846.4D5 is classified as bin 24.

[0239] In some embodiments, antibodies F847C.10B9, F847C.12F12, and F847C.26F5 are classified as bin 49. In some embodiments, any antibody that binds to any bin provided herein is contemplated.

[0240] In some embodiments, the anti-Gal3 antibodies or binding fragments thereof described herein can bind to the N-terminal domain of Gal3 or a portion thereof. In some embodiments, the anti-Gal3 antibodies or binding fragments thereof described herein can bind to an epitope of Gal3 that includes a GxYPG motif, where x is the amino acid alanine (A), glycine (G), or valine (V). In some embodiments, the anti-Gal3 antibodies or binding fragments thereof described herein can bind to an epitope of Gal3 that includes two GxYPG motifs separated by three amino acids, where x is A, G, or V.

[0241] 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.

[0242] In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a dissociation constant (KD) 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. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 1 nM. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 1.2 nM. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 2 nM. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 5 nM. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 10 nM. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 13.5 nM. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 15 nM. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 20 nM. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 25 nM. In some cases, the anti-Gal3 antibody or its binding fragment binds to Gal3 with a KD of less than 30 nM. Figure 36 KD values ​​for Gal3 binding of exemplary anti-Gal3 antibodies are provided.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.

[0243] Disclosed herein are anti-Gal3 antibodies or binding fragments thereof having specific sequences. In some embodiments, the anti-Gal3 antibodies or binding fragments thereof include (1) a heavy chain variable region comprising V H -CDR1, V H -CDR2 and V H - CDR3, and (2) light chain variable region, which includes V L -CDR1, V L -CDR2 and V L -CDR3. In some embodiments, V H - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 27-44, 245-246, 397-399, 588-615, V H - CDR2 comprises an amino acid sequence selected from SEQ ID NO: 45-60, 247-248, 400-406, 616-643, V H- CDR3 comprises an amino acid sequence selected from SEQ ID NO: 61-81, 249-250, 407-416, 644-671, V L - CDR1 comprises an amino acid sequence selected from SEQ ID NO: 82-101, 251-252, 417-426, 672-699, V L - CDR2 comprises an amino acid sequence selected from SEQ ID NO: 102-116, 253, 427-428, 700-727, and V L - CDR3 comprises an amino acid sequence selected from SEQ ID NOs: 117-135, 254-255, 429-434, 728-755. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein or any permutation of any anti-Gal3 antibody or binding fragment can be replaced with an antigen binding molecule that binds to Gal3.

[0244] In some embodiments, Figure 18 Depicts an exemplary V H -CDR1 sequence. In some embodiments, Figure 19 Depicts an exemplary V H -CDR2 sequence. In some embodiments, Figure 20 Depicts an exemplary V H -CDR3 sequence. In some embodiments, Figure 21 Depicts an exemplary V L -CDR1 sequence. In some embodiments, Figure 22 Depicts an exemplary V L -CDR2 sequence. In some embodiments, Figure 23 Depicts an exemplary V L - CDR3 sequence. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0245] In some embodiments, the heavy chain variable region (V H ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 136-160, 256-257, 435-450, 756-783. In some embodiments, the heavy chain variable region is selected from the group consisting of SEQ ID NOs: 136-160, 256-257, 435-450, 756-783. In some embodiments, Figure 24 Depicts an exemplary V HIn some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0246] In some embodiments, the light chain variable region (V L ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 161-187, 258-259, 451-464, 784-811. In some embodiments, the light chain variable region is selected from the group consisting of SEQ ID NOs: 161-187, 258-259, 451-464, 784-811. In some embodiments, Figure 25 Depicts an exemplary V L In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0247] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises 1) V in SEQ ID NO: 136 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 161 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 2) V within SEQ ID NO: 137 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 162 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 3) V within SEQ ID NO: 138H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 163 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 4) V within SEQ ID NO: 139 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 164 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 5) V within SEQ ID NO: 140 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 165 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 6) V within SEQ ID NO: 141 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 166 L -CDR1, V L -CDR2, V L-V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 7) V within SEQ ID NO: 142 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 167 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 8) V within SEQ ID NO: 143 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 168 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 9) SEQ ID NO: 144 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 169 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 10) V within SEQ ID NO: 145 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, VH -CDR3 and V within SEQ ID NO: 170 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 11) V within SEQ ID NO: 139 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 171 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 12) V within SEQ ID NO: 146 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 172 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 13) V within SEQ ID NO: 147 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 173 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 14) V within SEQ ID NO: 148 H -CDR1, VH -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 174 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 15) V within SEQ ID NO: 149 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 175 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 16) V within SEQ ID NO: 150 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 176 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 17) SEQ ID NO: 151 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 177 L -CDR1, V L -CDR2, V L -V of CDR3 L-CDR1, V L -CDR2, V L -CDR3; 18) V within SEQ ID NO:152 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:178 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 19) V within SEQ IDNO:153 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:179 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 20) V within SEQ ID NO:154 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:180 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 21) V within SEQ ID NO:155 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V<0000-CDR3 and V within SEQ ID NO: 181 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 22) SEQ ID NO: 156 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 182 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 23) SEQ ID NO: 157 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 183 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 24) SEQ ID NO: 155 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 184 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 25) V within SEQ ID NO: 158 H -CDR1, VH -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 185 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 26) V within SEQ ID NO: 159 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 186 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 27) SEQ ID NO: 160 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 187 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 28) SEQ ID NO: 256 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 258 L -CDR1, V L -CDR2, V L -V of CDR3 L-CDR1, V L -CDR2, V L -CDR3; 29) V within SEQ ID NO:257 H -CDR1, V H -CDR2, V H V of -CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:259 L -CDR1, V L -CDR2, V L V of -CDR3 L -CDR1, V L -CDR2, V L -CDR3; 30) V within SEQ ID NO:435 H -CDR1, V H -CDR2, V H V of -CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:185 L -CDR1, V L -CDR2, V L V of -CDR3 L ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​-CDR3 and V within SEQ ID NO: 452 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 33) SEQ ID NO: 438 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 453 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 34) V within SEQ ID NO: 439 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 162 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 35) SEQ ID NO: 440 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 454 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 36) SEQ ID NO: 441 V H -CDR1, VH -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 455 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 37) V within SEQ ID NO: 442 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 456 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 38) SEQ ID NO: 443 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 457 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 39) SEQ ID NO: 444 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 458 L -CDR1, V L -CDR2, V L -V of CDR3 L-CDR1, V L -CDR2, V L -CDR3; 40) SEQ ID NO: 445 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 459 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 41) SEQ ID NO: 446 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 460 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 42) SEQ ID NO: 447 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 461 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 43) SEQ ID NO: 448 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H-CDR3 and V within SEQ ID NO:462 L -CDR1, V L -CDR2, V L -CDR3's V L -CDR1, V L -CDR2, V L -CDR3; 44) V within SEQ ID NO:449 H -CDR1, V H -CDR2, V H -CDR3's V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:463 L -CDR1, V L -CDR2, V L -CDR3's V L -CDR1, V L -CDR2, V L -CDR3; 45) V within SEQ ID NO:450 H -CDR1, V H -CDR2, V<00005​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​-CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 785 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 48) SEQ ID NO: 758 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 786 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 49) SEQ ID NO: 759 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 787 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 50) SEQ ID NO: 760 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 788 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, VL -CDR2, V L -CDR3; 51) SEQ ID NO: 761 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 789 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 52) SEQ ID NO: 762 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 790 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 53) SEQ ID NO: 763 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 791 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 54) SEQ ID NO: 764 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 792L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 55) V within SEQ ID NO:765 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:793 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 56) V within SEQ ID NO:766 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:794 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 57) V within SEQ ID NO:767 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V<00007​​​​​​​​​​​​​​​​​​​​-V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 796 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 59) SEQ ID NO: 769 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 797 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 60) SEQ ID NO: 770 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 798 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 61) SEQ ID NO: 771 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 799 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, VL -CDR3; 62) SEQ ID NO: 772 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H - CDR3 and SEQ ID NO: 800 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 63) SEQ ID NO: 773 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 801 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 64) SEQ ID NO: 774 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 802 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 65) SEQ ID NO: 775 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 803 L -CDR1, VL -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 66) SEQ ID NO: 776 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 804 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 67) SEQ ID NO: 777 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 805 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 68) SEQ ID NO: 778 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 806 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 69) SEQ ID NO: 779 V H -CDR1, V H -CDR2, V H -V of CDR3 H-CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:807 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 70) V within SEQ ID NO:780 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:808 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 71) V within SEQ ID NO:781 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:809 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 72) V within SEQ ID NO:782 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:810 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L-CDR3; or 73) SEQ ID NO: 783 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 811 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3.

[0248] In some embodiments, Figure 28 Depicted are exemplary combinations of heavy chain variable region CDRs. In some embodiments, Figure 29 Exemplary combinations of light chain variable region CDRs are depicted.In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein or any permutation of any anti-Gal3 antibody or binding fragment can be replaced with an antigen binding molecule that binds to Gal3.

[0249] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises 1) a heavy chain variable region of SEQ ID NO: 136 and a light chain variable region of SEQ ID NO: 161; 2) a heavy chain variable region of SEQ ID NO: 137 and a light chain variable region of SEQ ID NO: 162; 3) a heavy chain variable region of SEQ ID NO: 138 and a light chain variable region of SEQ ID NO: 163; 4) a heavy chain variable region of SEQ ID NO: 139 and a light chain variable region of SEQ ID NO: 164; 5) a heavy chain variable region of SEQ ID NO: 140 and a light chain variable region of SEQ ID NO: 165; 6) a heavy chain variable region of SEQ ID NO: 141 and a light chain variable region of SEQ ID NO: 166; 7) a heavy chain variable region of SEQ ID NO: 142 and a light chain variable region of SEQ ID NO: 167; 8) a heavy chain variable region of SEQ ID NO: 143 and a light chain variable region of SEQ ID NO: 168; 9) a heavy chain variable region of SEQ ID NO: 144 and a light chain variable region of SEQ ID NO: 145. NO: 144 heavy chain variable region and SEQ ID NO: 169 light chain variable region; 10) SEQ ID NO: 145 heavy chain variable region and SEQ ID NO: 170 light chain variable region; 11) SEQ ID NO: 139 heavy chain variable region and SEQ ID NO: 171 light chain variable region; 12) SEQ ID NO: 146 heavy chain variable region and SEQ ID NO: 172 light chain variable region; 13) SEQ ID NO: 147 heavy chain variable region and SEQ ID NO: 173 light chain variable region; 14) SEQ ID NO: 148 heavy chain variable region and SEQ ID NO: 174 light chain variable region; 15) SEQ ID NO: 149 heavy chain variable region and SEQ ID NO: 175 light chain variable region; 16) SEQ ID NO: 150 heavy chain variable region and SEQ ID NO: 176 light chain variable region; 17) SEQ ID NO: 151 heavy chain variable region and SEQ ID NO: 152 light chain variable region; NO: 177; 18) the heavy chain variable region of SEQ ID NO: 152 and the light chain variable region of SEQ ID NO: 178; 19) the heavy chain variable region of SEQ ID NO: 153 and the light chain variable region of SEQ ID NO: 179; 20) the heavy chain variable region of SEQ ID NO: 154 and the light chain variable region of SEQ ID NO: 180; 21) the heavy chain variable region of SEQ ID NO: 155 and the light chain variable region of SEQ ID NO: 181; 22) the heavy chain variable region of SEQ ID NO: 156 and the light chain variable region of SEQ ID NO: 182; 23) the heavy chain variable region of SEQ ID NO: 157 and the light chain variable region of SEQ ID NO: 183;24) the heavy chain variable region of SEQ ID NO: 155 and the light chain variable region of SEQ ID NO: 184; 25) the heavy chain variable region of SEQ ID NO: 158 and the light chain variable region of SEQ ID NO: 185; 26) the heavy chain variable region of SEQ ID NO: 159 and the light chain variable region of SEQ ID NO: 186; 27) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 187; 28) the heavy chain variable region of SEQ ID NO: 256 and the light chain variable region of SEQ ID NO: 258; 29) the heavy chain variable region of SEQ ID NO: 257 and the light chain variable region of SEQ ID NO: 259; 30) the heavy chain variable region of SEQ ID NO: 435 and the light chain variable region of SEQ ID NO: 185; 31) the heavy chain variable region of SEQ ID NO: 436 and the light chain variable region of SEQ ID NO: 451; 32) the heavy chain variable region of SEQ ID NO: 437 and the light chain variable region of SEQ ID NO: 450; NO: 437 heavy chain variable region and SEQ ID NO: 452 light chain variable region; 33) SEQ ID NO: 438 heavy chain variable region and SEQ ID NO: 453 light chain variable region; 34) SEQ ID NO: 439 heavy chain variable region and SEQ ID NO: 162 light chain variable region; 35) SEQ ID NO: 440 heavy chain variable region and SEQ ID NO: 454 light chain variable region; 36) SEQ ID NO: 441 heavy chain variable region and SEQ ID NO: 455 light chain variable region; 37) SEQ ID NO: 442 heavy chain variable region and SEQ ID NO: 456 light chain variable region; 38) SEQ ID NO: 443 heavy chain variable region and SEQ ID NO: 457 light chain variable region; 39) SEQ ID NO: 444 heavy chain variable region and SEQ ID NO: 458 light chain variable region; 40) SEQ ID NO: 445 heavy chain variable region and SEQ ID NO: 446 light chain variable region; NO:459; 41) the heavy chain variable region of SEQ ID NO:446 and the light chain variable region of SEQ ID NO:460; 42) the heavy chain variable region of SEQ ID NO:447 and the light chain variable region of SEQ ID NO:461; 43) the heavy chain variable region of SEQ ID NO:448 and the light chain variable region of SEQ ID NO:462; 44) the heavy chain variable region of SEQ ID NO:449 and the light chain variable region of SEQ ID NO:463; 45) the heavy chain variable region of SEQ ID NO:450 and the light chain variable region of SEQ ID NO:464; 46) the heavy chain variable region of SEQ ID NO:756 and the light chain variable region of SEQ ID NO:784;47) the heavy chain variable region of SEQ ID NO: 757 and the light chain variable region of SEQ ID NO: 785; 48) the heavy chain variable region of SEQ ID NO: 758 and the light chain variable region of SEQ ID NO: 786; 49) the heavy chain variable region of SEQ ID NO: 759 and the light chain variable region of SEQ ID NO: 787; 50) the heavy chain variable region of SEQ ID NO: 760 and the light chain variable region of SEQ ID NO: 788; 51) the heavy chain variable region of SEQ ID NO: 761 and the light chain variable region of SEQ ID NO: 789; 52) the heavy chain variable region of SEQ ID NO: 762 and the light chain variable region of SEQ ID NO: 790; 53) the heavy chain variable region of SEQ ID NO: 763 and the light chain variable region of SEQ ID NO: 791; 54) the heavy chain variable region of SEQ ID NO: 764 and the light chain variable region of SEQ ID NO: 792; 55) the heavy chain variable region of SEQ ID NO: 765 and the light chain variable region of SEQ ID NO: 766; NO: 765 heavy chain variable region and SEQ ID NO: 793 light chain variable region; 56) SEQ ID NO: 766 heavy chain variable region and SEQ ID NO: 794 light chain variable region; 57) SEQ ID NO: 767 heavy chain variable region and SEQ ID NO: 795 light chain variable region; 58) SEQ ID NO: 768 heavy chain variable region and SEQ ID NO: 796 light chain variable region; 59) SEQ ID NO: 769 heavy chain variable region and SEQ ID NO: 797 light chain variable region; 60) SEQ ID NO: 770 heavy chain variable region and SEQ ID NO: 798 light chain variable region; 61) SEQ ID NO: 771 heavy chain variable region and SEQ ID NO: 799 light chain variable region; 62) SEQ ID NO: 772 heavy chain variable region and SEQ ID NO: 800 light chain variable region; 63) SEQ ID NO: 773 heavy chain variable region and SEQ ID NO: NO: 801; 64) the heavy chain variable region of SEQ ID NO: 774 and the light chain variable region of SEQ ID NO: 802; 65) the heavy chain variable region of SEQ ID NO: 775 and the light chain variable region of SEQ ID NO: 803; 66) the heavy chain variable region of SEQ ID NO: 776 and the light chain variable region of SEQ ID NO: 804; 67) the heavy chain variable region of SEQ ID NO: 777 and the light chain variable region of SEQ ID NO: 805; 68) the heavy chain variable region of SEQ ID NO: 778 and the light chain variable region of SEQ ID NO: 806; 69) the heavy chain variable region of SEQ ID NO: 779 and the light chain variable region of SEQ ID NO: 807;70) the heavy chain variable region of SEQ ID NO: 780 and the light chain variable region of SEQ ID NO: 808; 71) the heavy chain variable region of SEQ ID NO: 781 and the light chain variable region of SEQ ID NO: 809; 72) the heavy chain variable region of SEQ ID NO: 782 and the light chain variable region of SEQ ID NO: 810; or 73) the heavy chain variable region of SEQ ID NO: 783 and the light chain variable region of SEQ ID NO: 811.

[0250] In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0251] In some embodiments, the anti-Gal3 antibody or its binding fragment comprises a heavy chain (HC) sequence of any one of SEQ ID NOs: 188-216, 465-482. Figure 26 Exemplary HC sequences are depicted.In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment, can be replaced with an antigen binding molecule that binds to Gal3.

[0252] In some embodiments, the anti-Gal3 antibody or its binding fragment comprises a light chain (LC) sequence of any one of SEQ ID NOs: 217-243, 483-499. Figure 27 Exemplary LC sequences are depicted.In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment, can be replaced with an antigen binding molecule that binds to Gal3.

[0253] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from TB001 (IMT001), TB006 (4A11.H3L1), 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, F846C.1B2, F846C.1F5, F846C.1H12, and F846C. 46C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C. 12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 847.14H4, 846T.1H2, mIMT001, 4A1 1.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E 5. 23B10.2B12, 24D12.2H9, 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, or a binding fragment thereof. In some embodiments, Figure 30 The heavy and light chain CDRs associated with each of the aforementioned antibodies are depicted in . In some embodiments, Figure 31 The V associated with each of the aforementioned antibodies is depicted. H and V L In some embodiments, Figure 32 The HC and LC associated with each of the aforementioned antibodies are depicted.In some embodiments, any anti-Gal3 antibody or binding fragment thereof or any permutation of any anti-Gal3 antibody or binding fragment provided herein can be replaced with an antigen binding molecule that binds to Gal3.

[0254] Disclosed herein are anti-Gal3 antibodies or binding fragments thereof. In some embodiments, the anti-Gal3 antibodies or binding fragments thereof include (1) a heavy chain variable region comprising V H -CDR1, V H -CDR2 and V H - CDR3, and (2) light chain variable region, which includes V L -CDR1, V L -CDR2 and V L -CDR3. In some embodiments, V H - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 36-44, 588-615, V H - CDR2 comprises an amino acid sequence selected from SEQ ID NOs: 54-60, 616-643, V H - CDR3 comprises an amino acid sequence selected from SEQ ID NOs: 70-81, 644-671, V L - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 92-101, 672-699, V L - CDR2 comprises an amino acid sequence selected from SEQ ID NO: 111-116, 700-727, and V L - CDR3 comprises an amino acid sequence selected from SEQ ID NOs: 127-135, 728-755. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein or any permutation of any anti-Gal3 antibody or binding fragment can be replaced with an antigen binding molecule that binds to Gal3.

[0255] In some embodiments, Figure 18 An exemplary V H -CDR1 sequence. In some embodiments, Figure 19 An exemplary V H -CDR2 sequence. In some embodiments, Figure 20 An exemplary V H -CDR3 sequence. In some embodiments, Figure 21 An exemplary V L -CDR1 sequence. In some embodiments, Figure 22 An exemplary V L -CDR2 sequence. In some embodiments, Figure 23 An exemplary V L - CDR3 sequence. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0256] In some embodiments, the heavy chain variable region (V H ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 147-160, 756-783. In some embodiments, the heavy chain variable region is selected from the group consisting of SEQ ID NOs: 147-160, 756-783. In some embodiments, Figure 24 An exemplary V H In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0257] In some embodiments, the light chain variable region (V L ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 173-187, 784-811. In some embodiments, the light chain variable region is selected from the group consisting of SEQ ID NOs: 173-187, 784-811. In some embodiments, Figure 25 An exemplary V L In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0258] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises 1) V in SEQ ID NO: 147 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 173 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 2) V within SEQ ID NO: 148 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H-CDR2, V H -CDR3 and V within SEQ ID NO: 174 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 3) V within SEQ ID NO: 149 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 175 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 4) V within SEQ ID NO: 150 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 176 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 5) V within SEQ ID NO: 151 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 177 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 6) V within SEQ ID NO: 152 H-CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -V within CDR3 and SEQ ID NO:178 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 7) V within SEQ ID NO:153 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -V within CDR3 and SEQ ID NO:179 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 8) V within SEQ ID NO:154 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -V within CDR3 and SEQ ID NO:180 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 9) V within SEQ ID NO:155 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -V within CDR3 and SEQ ID NO:181 L -CDR1, V L -CDR2, V L -V of CDR3 L-CDR1, V L -CDR2, V L -CDR3; 10) V within SEQ ID NO: 156 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 182 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 11) V within SEQ ID NO: 157 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 183 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 12) SEQ ID NO: 155 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 184 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 13) SEQ ID NO: 158 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H-CDR3 and V within SEQ ID NO: 185 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 14) V within SEQ ID NO: 159 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 186 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 15) SEQ ID NO: 160 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 187 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 16) SEQ ID NO: 756 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 784 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 17) SEQ ID NO: 757 V H -CDR1, V H-CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 785 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 18) SEQ ID NO: 758 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 786 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 19) SEQ ID NO: 759 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 787 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 20) SEQ ID NO: 760 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 788 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, VL - CDR2, V L - CDR3; 21) V within SEQ ID NO:761 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:789 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 22) V within SEQ ID NO:762 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:790 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 23) V within SEQ ID NO:763 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:791 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 24) V within SEQ ID NO:764 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:792L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 25) SEQ ID NO: 765 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 793 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 26) SEQ ID NO: 766 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 794 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 27) SEQ ID NO: 767 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 795 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 28) SEQ ID NO: 768 V H -CDR1, V H -CDR2, V H-V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 796 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 29) SEQ ID NO: 769 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 797 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 30) SEQ ID NO: 770 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 798 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 31) SEQ ID NO: 771 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 799 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, VL - CDR3; 32) V within SEQ ID NO:772 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:800 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 33) V within SEQ ID NO:773 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:801 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 34) V within SEQ ID NO:774 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:802 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 35) V within SEQ ID NO:775 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:803 L - CDR1, VL -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 36) SEQ ID NO: 776 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 804 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 37) SEQ ID NO: 777 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 805 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 38) SEQ ID NO: 778 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 806 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 39) SEQ ID NO: 779 V H -CDR1, V H -CDR2, V H -V of CDR3 H-CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 807 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 40) SEQ ID NO: 780 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 808 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 41) SEQ ID NO: 781 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 809 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 42) SEQ ID NO: 782 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 810 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L-CDR3; or 43) V within SEQ ID NO: 783 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 811 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3. In some embodiments, Figure 28 Exemplary combinations of heavy chain variable region CDRs are depicted in . In some embodiments, Figure 29 Exemplary combinations of light chain variable region CDRs are depicted in In some embodiments, any anti-Gal3 antibody or binding fragment thereof or any permutation of any anti-Gal3 antibody or binding fragment provided herein can be replaced with an antigen binding molecule that binds to Gal3.

[0259] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises 1) a heavy chain variable region of SEQ ID NO: 147 and a light chain variable region of SEQ ID NO: 173; 2) a heavy chain variable region of SEQ ID NO: 148 and a light chain variable region of SEQ ID NO: 174; 3) a heavy chain variable region of SEQ ID NO: 149 and a light chain variable region of SEQ ID NO: 175; 4) a heavy chain variable region of SEQ ID NO: 150 and a light chain variable region of SEQ ID NO: 176; 5) a heavy chain variable region of SEQ ID NO: 151 and a light chain variable region of SEQ ID NO: 177; 6) a heavy chain variable region of SEQ ID NO: 152 and a light chain variable region of SEQ ID NO: 178; 7) a heavy chain variable region of SEQ ID NO: 153 and a light chain variable region of SEQ ID NO: 179; 8) a heavy chain variable region of SEQ ID NO: 154 and a light chain variable region of SEQ ID NO: 180; 9) a heavy chain variable region of SEQ ID NO: 181 and a light chain variable region of SEQ ID NO: 182; NO: 155 and the light chain variable region of SEQ ID NO: 181; 10) the heavy chain variable region of SEQ ID NO: 156 and the light chain variable region of SEQ ID NO: 182; 11) the heavy chain variable region of SEQ ID NO: 157 and the light chain variable region of SEQ ID NO: 183; 12) the heavy chain variable region of SEQ ID NO: 155 and the light chain variable region of SEQ ID NO: 184; 13) the heavy chain variable region of SEQ ID NO: 158 and the light chain variable region of SEQ ID NO: 185; 14) the heavy chain variable region of SEQ ID NO: 159 and the light chain variable region of SEQ ID NO: 186; 15) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 187; 16) the heavy chain variable region of SEQ ID NO: 756 and the light chain variable region of SEQ ID NO: 784; 17) the heavy chain variable region of SEQ ID NO: 757 and the light chain variable region of SEQ ID NO: NO: 785; 18) the heavy chain variable region of SEQ ID NO: 758 and the light chain variable region of SEQ ID NO: 786; 19) the heavy chain variable region of SEQ ID NO: 759 and the light chain variable region of SEQ ID NO: 787; 20) the heavy chain variable region of SEQ ID NO: 760 and the light chain variable region of SEQ ID NO: 788; 21) the heavy chain variable region of SEQ ID NO: 761 and the light chain variable region of SEQ ID NO: 789; 22) the heavy chain variable region of SEQ ID NO: 762 and the light chain variable region of SEQ ID NO: 790; 23) the heavy chain variable region of SEQ ID NO: 763 and the light chain variable region of SEQ ID NO: 791;24) the heavy chain variable region of SEQ ID NO: 764 and the light chain variable region of SEQ ID NO: 792; 25) the heavy chain variable region of SEQ ID NO: 765 and the light chain variable region of SEQ ID NO: 793; 26) the heavy chain variable region of SEQ ID NO: 766 and the light chain variable region of SEQ ID NO: 794; 27) the heavy chain variable region of SEQ ID NO: 767 and the light chain variable region of SEQ ID NO: 795; 28) the heavy chain variable region of SEQ ID NO: 768 and the light chain variable region of SEQ ID NO: 796; 29) the heavy chain variable region of SEQ ID NO: 769 and the light chain variable region of SEQ ID NO: 797; 30) the heavy chain variable region of SEQ ID NO: 770 and the light chain variable region of SEQ ID NO: 798; 31) the heavy chain variable region of SEQ ID NO: 771 and the light chain variable region of SEQ ID NO: 799; 32) NO: 772 heavy chain variable region and SEQ ID NO: 800 light chain variable region; 33) SEQ ID NO: 773 heavy chain variable region and SEQ ID NO: 801 light chain variable region; 34) SEQ ID NO: 774 heavy chain variable region and SEQ ID NO: 802 light chain variable region; 35) SEQ ID NO: 775 heavy chain variable region and SEQ ID NO: 803 light chain variable region; 36) SEQ ID NO: 776 heavy chain variable region and SEQ ID NO: 804 light chain variable region; 37) SEQ ID NO: 777 heavy chain variable region and SEQ ID NO: 805 light chain variable region; 38) SEQ ID NO: 778 heavy chain variable region and SEQ ID NO: 806 light chain variable region; 39) SEQ ID NO: 779 heavy chain variable region and SEQ ID NO: 807 light chain variable region; 40) SEQ ID NO: 780 heavy chain variable region and SEQ ID NO: 41) the heavy chain variable region of SEQ ID NO: 781 and the light chain variable region of SEQ ID NO: 809; 42) the heavy chain variable region of SEQ ID NO: 782 and the light chain variable region of SEQ ID NO: 810; or 43) the heavy chain variable region of SEQ ID NO: 783 and the light chain variable region of SEQ ID NO: 811. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any arrangement of any anti-Gal3 antibody or binding fragment, can be replaced with an antigen-binding molecule that binds to Gal3.

[0260] In some embodiments, the anti-Gal3 antibody or its binding fragment comprises a heavy chain (HC) sequence of any one of SEQ ID NOs: 201-216. Figure 26 Exemplary HC sequences are depicted in In some embodiments, any anti-Gal3 antibody or binding fragment thereof or any permutation of any anti-Gal3 antibody or binding fragment provided herein can be replaced with an antigen binding molecule that binds to Gal3.

[0261] In some embodiments, the anti-Gal3 antibody or its binding fragment comprises a light chain (LC) sequence of any one of SEQ ID NOs: 229-243. Figure 27 Exemplary LC sequences are depicted in In some embodiments, any anti-Gal3 antibody or binding fragment thereof or any permutation of any anti-Gal3 antibody or binding fragment provided herein can be replaced with an antigen binding molecule that binds to Gal3.

[0262] In some embodiments, the anti-Gal3 antibody or its binding fragment is selected from at least one of the group consisting of F846C.1B2, F846C.1F5, F846C.1H12, F846C.2H3, F846TC.14E4, F846TC.16B5, F846TC.7F10, F849C.8D10, 846.4D5 or its binding fragment. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 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 and / or F847C.21H6, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody selected from 846.4D5, 15F10.2D6, F846C.1B2, and F846C.1H12. Figure 30 Depicted are the heavy and light chain CDRs associated with each of the aforementioned antibodies. In some embodiments, Figure 31 The V associated with each of the aforementioned antibodies is depicted. H and V L In some embodiments, Figure 32 The HC and LC associated with each of the aforementioned antibodies are depicted.In some embodiments, any anti-Gal3 antibody or binding fragment thereof or any permutation of any anti-Gal3 antibody or binding fragment provided herein can be replaced with an antigen binding molecule that binds to Gal3.

[0263] In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to one or more peptides of SEQ ID NOs: 3 to 26. In some embodiments, any anti-Gal3 antibody or binding fragment thereof provided herein, or any permutation of any anti-Gal3 antibody or binding fragment thereof, can be replaced with an antigen binding molecule that binds to Gal3.

[0264] In some embodiments, the anti-Gal3 antibody or binding fragment thereof belongs to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof competes with an antibody belonging to bin 3, 8, 17, or 24 for binding to Gal3.

[0265] In some cases, the anti-Gal3 antibody or its binding fragment comprises a humanized antibody or its binding fragment. In other cases, the anti-Gal3 antibody or its binding fragment comprises a chimeric antibody or its binding fragment. In some cases, the anti-Gal3 antibody comprises a full-length antibody or its binding fragment. In some cases, the anti-Gal3 antibody or its binding fragment comprises a bispecific antibody or its binding fragment. In some cases, the anti-Gal3 antibody or its binding fragment 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 its binding fragment.

[0266] In some embodiments, methods of using any of the anti-Gal3 antibodies, binding fragments thereof, or antigen-binding molecules disclosed herein for treating a disease or disorder in a subject are disclosed. In some embodiments, the methods comprise administering any of the anti-Gal3 antibodies, binding fragments thereof, or antigen-binding molecules disclosed herein to a subject who has, is suspected of having, or is at risk of developing a disease or disorder described herein.

[0267] In some embodiments, any of the embodiments and / or any anti-Gal3 antibodies or binding fragments thereof disclosed herein can be used in any of the applications, methods, and uses provided herein.

[0268] Some embodiments provided herein relate to 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.

[0269] Some embodiments provided herein relate to anti-Gal3 antibodies or binding fragments thereof that disrupt the interaction between Gal3 and proteins associated with primary diseases or neurological diseases. In some embodiments, the anti-Gal3 antibodies and binding fragments thereof disclosed herein are methods and uses for treating primary diseases and / or neurological diseases.

[0270] Some embodiments provided herein relate to anti-Gal3 antibodies or binding fragments thereof capable of crossing the blood-brain barrier. In some embodiments, the blood-brain barrier is that of a subject suffering from a neurological disease. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is a multispecific antibody to improve the penetration of another antibody across the blood-brain barrier. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is conjugated to a cargo to improve the penetration of the cargo across the blood-brain barrier.

[0271] Some embodiments provided herein relate to anti-Gal3 antibodies or binding fragments thereof that disrupt the interaction between Gal3 and cell surface markers or tumor cell surface markers. In some embodiments, the anti-Gal3 antibodies and binding fragments thereof disclosed herein are used to treat diseases associated with cell surface markers or tumor cell surface markers. In some embodiments, the disease is cancer, fibrosis, or an immune-related disorder.

[0272] Also disclosed herein are proteins comprising Figure 18-27 In some embodiments, the protein is an antibody or a binding fragment thereof. In some embodiments, the protein comprises a) a) a peptide sequence having at least 80%, 85%, 90%, 95%, 99% or 100% identity to one or more peptide sequences of the invention. Figure 18 V has at least 80%, 85%, 90%, 95%, 99% or 100% homology to one or more peptide sequences H -CDR1 peptide sequence; b) with Figure 19 V has at least 80%, 85%, 90%, 95%, 99% or 100% homology to one or more peptide sequences H -CDR2 peptide sequence; c) with Figure 20 V has at least 80%, 85%, 90%, 95%, 99% or 100% homology to one or more peptide sequences H -CDR3 peptide sequence; d) with Figure 21 V has at least 80%, 85%, 90%, 95%, 99% or 100% homology to one or more peptide sequences L -CDR1 peptide sequence; e) with Figure 22 V has at least 80%, 85%, 90%, 95%, 99% or 100% homology to one or more peptide sequences L-CDR2 peptide sequence; f) with Figure 23 V has at least 80%, 85%, 90%, 95%, 99% or 100% homology to one or more peptide sequences L -CDR3 peptide sequence; g) with Figure 24 h) a heavy chain variable region peptide sequence that is at least 80%, 85%, 90%, 95%, 99% or 100% homologous to one or more peptide sequences of Figure 25 a light chain variable region peptide sequence that is at least 80%, 85%, 90%, 95%, 99% or 100% homologous to one or more peptide sequences of Figure 26 j) a heavy chain peptide sequence that is at least 80%, 85%, 90%, 95%, 99% or 100% homologous to one or more peptide sequences of Figure 27 or any combination thereof, comprising one or more of the provided sequences or a combination of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 of the provided sequences. In some embodiments, the protein comprises a light chain peptide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% homology to one or more of the provided sequences; or any combination thereof, comprising one of the provided sequences or a combination of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 of the provided sequences. Figures 37-40 The peptide sequence encoded by any one or more nucleic acid sequences of the peptide sequence has at least 80%, 85%, 90%, 95%, 99% or 100% homology to the peptide sequence. In some embodiments, the protein is an antibody or binding fragment thereof that binds to Gal3. How to use

[0273] In some embodiments, any of the constructs provided herein can be used in neurological disorders and / or primary diseases.

[0274] Disclosed herein are methods for treating a neurological disorder in a subject in need thereof. The method comprises administering to the subject an effective amount of an anti-Gal3 antibody or a binding fragment thereof, thereby treating the neurological disorder. In some embodiments, the method further comprises selecting the subject as having a neurological disorder or being at risk of having a neurological disorder before the administering step. In some embodiments, the method further comprises detecting an improvement in symptoms associated with the neurological disorder after the administering step. In some embodiments, the neurological disorder comprises inflammation, encephalitis, Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, olfactory dysfunction, aphasia, Bell's palsy, transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease, fatal familial insomnia, epilepsy, spasticity, neurodevelopmental, Tourette syndrome, neuroinfectious diseases, meningitis, encephalitis, mad cow disease, West Nile virus encephalitis, neuro-AIDS, fragile X syndrome, Guillain-Barré syndrome, brain metastasis or brain cancer or any combination thereof. In some embodiments, the neurological disorder is Alzheimer's disease, and the anti-Gal3 antibody or its binding fragment disrupts the binding between Gal3 and amyloid precursor protein (APP) or amyloid beta (Aβ), or both. In some embodiments, APP comprises the sequence of APP695 (SEQ ID NO: 2). In some embodiments, Aβ comprises Aβ monomers, Aβ oligomers, Aβ fibrils, or any combination thereof. In some embodiments, Aβ comprises the sequence of Aβ42 (SEQ ID NO: 244). In some embodiments, the anti-Gal3 antibody or its binding fragment reduces the binding between Gal3 and APP or Aβ, or both, by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or any percentage within a range bounded by any two of the foregoing percentages. In some embodiments, the anti-Gal3 antibody or its binding fragment promotes phagocytosis of microglia in a subject. In some embodiments, the anti-Gal3 antibody or binding fragment thereof inhibits Aβ-mediated activation of microglia in a subject. In some embodiments, Aβ-mediated activation of microglia is inhibited by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or any percentage within a range bounded by any two of the foregoing percentages. In some embodiments, the anti-Gal3 antibody or binding fragment thereof inhibits Aβ fibril or oligomer formation in a subject. In some embodiments, Aβ fibril or oligomer formation is inhibited by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or any percentage within a range bounded by any two of the foregoing percentages.In some embodiments, the anti-Gal3 antibody or its binding fragment promotes neuronal regeneration in the subject. In some embodiments, the anti-Gal3 antibody or its binding fragment disrupts the binding between Gal3 and Toll-like receptor 4 (TLR4) or triggering receptor 2 on myeloid cells (TREM2) or the two. In some embodiments, the binding between Gal3 and TLR4 or TREM2 or the two is disrupted by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% or any percentage within the range defined by any two of the above percentages. In some embodiments, more than one anti-Gal3 antibody or its binding fragment is administered to the subject. In some embodiments, the anti-Gal3 antibody or its binding fragment is administered together with one or more additional therapeutic compositions. In some embodiments, one or more additional therapeutic compositions include a cholinesterase inhibitor, an NMDA receptor antagonist, or both. In some embodiments, the cholinesterase inhibitor comprises tacrine, rivastigmine, galantamine, donepezil, or any combination thereof. In some embodiments, the NMDA receptor antagonist comprises memantine.

[0275] Also disclosed herein are methods for disrupting the binding between Gal3 and APP or Aβ or both. In some embodiments, the method comprises contacting APP or Aβ or both with an anti-Gal3 antibody or a binding fragment thereof, thereby disrupting the binding between Gal3 and APP. In some embodiments, APP or Aβ or both are soluble or part of a first cell. In some embodiments, Gal3 is soluble or part of a second cell. In some embodiments, APP comprises the sequence of APP695 (SEQ ID NO: 2). In some embodiments, Aβ comprises Aβ monomers, Aβ oligomers, Aβ fibrils, or any combination thereof. In some embodiments, Aβ comprises the sequence of Aβ42 (SEQ ID NO: 244). In some embodiments, the anti-Gal3 antibody or binding fragment thereof reduces binding between Gal3 and APP or Aβ, or both, by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or any percentage within a range bounded by any two of the foregoing percentages. In some embodiments, the anti-Gal3 antibody or binding fragment thereof reduces binding between Gal3 and APP or Aβ, or both, by at least 85%. In some embodiments, the anti-Gal3 antibody or binding fragment thereof reduces binding between Gal3 and APP or Aβ, or both, by at least 90%. In some embodiments, the anti-Gal3 antibody or binding fragment thereof reduces binding between Gal3 and APP or Aβ, or both, by at least 95%. In some embodiments, APP is contacted with more than one anti-Gal3 antibody or binding fragment thereof. In some embodiments, Aβ is Aβ peptide or Aβ aggregates, or both. In some embodiments, Aβ aggregates are Aβ fibrils or Aβ oligomers, or both.

[0276] Also disclosed herein are methods for treating a primary disease in a subject in need thereof. In some embodiments, the method comprises administering an effective amount of an anti-Gal3 antibody or a binding fragment thereof to the subject, thereby treating the subject's primary disease. In some embodiments, the method further comprises, prior to the administering step, selecting the subject as having or at risk of having the primary disease. In some embodiments, the method further comprises, after the administering step, detecting improvement in symptoms associated with the primary disease. In some embodiments, treating the primary disease comprises treating the subject's active primary disease or providing a prophylactic treatment, or both. In some embodiments, the underlying disease comprises Alzheimer's disease, cerebral beta amyloid angiopathy, glaucoma, retinal ganglion cell degeneration, Parkinson's disease, Lewy dementia, multiple system atrophy, synucleinopathy, Pick's disease, corticobasal degeneration, tauopathy, frontotemporal lobar degeneration, Huntington's disease, dentatorubral pallidum Lewy body atrophy, spinal bulbar muscular atrophy, spinocerebellar ataxia, fragile X syndrome, Baratela-Scott syndrome, Friedreich's ataxia, myotonic dystrophy, Alexander disease, familial British dementia, familial Danish dementia, Peyton-Stokes disease, and other neurological disorders. Syphilis, seipin protein disease, AA (secondary) amyloidosis, type II diabetes, fibrinogen amyloidosis, dialysis amyloidosis, inclusion body myositis / myopathy, familial amyloidosis neuropathy, senile systemic amyloidosis, serpentine lesions, cardiac atrial amyloidosis, pituitary prolactinoma, insulin amyloidosis, corneal lactoferrin amyloidosis, pulmonary alveolar proteinosis, seminal vesicle amyloidosis, cutaneous lichen amyloidosis, Mallory body or odontogenic (Pindborg) tumor amyloid or any disease caused by protein misfolding or aggregation or any combination thereof. In some embodiments, more than one anti-Gal3 antibody or its binding fragment is administered to the subject. In some embodiments, the anti-Gal3 antibody or its binding fragment is administered together with one or more additional therapeutic compositions. In some embodiments, one or more additional therapeutic compositions include cholinesterase inhibitors, NMDA receptor antagonists, insulin or any combination thereof. In some embodiments, the cholinesterase inhibitor comprises tacrine, rivastigmine, galantamine, donepezil, or any combination thereof. In some embodiments, the NMDA receptor antagonist comprises memantine.

[0277] Also disclosed herein are methods of administering an antibody to a subject. In some embodiments, the method comprises administering an anti-Gal3 antibody or a binding fragment thereof to the subject. In some embodiments, the method further comprises, prior to the administering step, selecting the subject as having or at risk of a neurological disease or primary disease. In some embodiments, the neurological disorder comprises inflammation, encephalitis, Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, olfactory dysfunction, aphasia, Bell's palsy, transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease, fatal familial insomnia, epilepsy, spasticity, neurodevelopmental, Tourette syndrome, neuroinfectious diseases, meningitis, encephalitis, mad cow disease, West Nile virus encephalitis, neuro-AIDS, fragile X syndrome, Guillain-Barré syndrome, brain metastasis, brain cancer, or any combination thereof. In some embodiments, the neurological disorder is Alzheimer's disease. In some embodiments, the underlying disease comprises Alzheimer's disease, cerebral beta amyloid angiopathy, glaucoma, retinal ganglion cell degeneration, Parkinson's disease, Lewy dementia, multiple system atrophy, synucleinopathy, Pick's disease, corticobasal degeneration, tauopathy, frontotemporal lobar degeneration, Huntington's disease, dentatorubral pallidum Lewy body atrophy, spinal bulbar muscular atrophy, spinocerebellar ataxia, fragile X syndrome, Baratela-Scott syndrome, Friedreich's ataxia, myotonic dystrophy, Alexander disease, familial British dementia, familial Danish dementia, Peyer's disease, Syphilis, seipin disease, AA (secondary) amyloidosis, type II diabetes, fibrinogen amyloidosis, dialysis amyloidosis, inclusion body myositis / myopathy, familial amyloidosis neuropathy, senile systemic amyloidosis, serpentine lesions, cardiac atrial amyloidosis, pituitary prolactinoma, insulin amyloidosis, corneal lactoferrin amyloidosis, pulmonary alveolar proteinosis, seminal vesicle amyloidosis, cutaneous lichen amyloidosis, Mallory body or odontogenic (Pindborg) tumor amyloid, or any disease or any combination thereof caused by protein misfolding or aggregation. In some embodiments, more than one anti-Gal3 antibody or binding fragment thereof is administered to the subject.

[0278] Also disclosed herein are methods for treating brain cancer in a subject in need thereof. In some embodiments, the methods comprise administering to the subject an effective amount of an anti-Gal3 antibody or a binding fragment thereof, thereby treating the subject's brain cancer. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is capable of crossing the blood-brain barrier. In some embodiments, administration of the anti-Gal3 antibody or binding fragment thereof induces apoptosis in brain cancer cells.

[0279] Also disclosed herein is a method for promoting neuronal regeneration in a subject in need thereof. In some embodiments, the method comprises administering an effective amount of an anti-Gal3 antibody or its binding fragment to the subject, thereby promoting neuronal regeneration in the subject. In some embodiments, the method further comprises selecting the subject as suffering from neuronal degeneration or being at risk of suffering from neuronal degeneration before the administering step. In some embodiments, the method further comprises detecting neuronal regeneration in the subject after the administering step. In some embodiments, the subject comprises neuronal degeneration associated with inflammation, encephalitis, Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, olfactory dysfunction, aphasia, Bell's palsy, transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease, fatal familial insomnia, epilepsy, spasticity, neurodevelopmental disease, Tourette syndrome, neuroinfectious diseases, meningitis, encephalitis, mad cow disease, West Nile virus encephalitis, neuro-AIDS, fragile X syndrome, Guillain-Barré syndrome, brain metastasis, brain cancer, or any combination thereof. In some embodiments, the neuronal degeneration is associated with Alzheimer's disease, and the anti-Gal3 antibody or binding fragment thereof disrupts the binding between Gal3 and amyloid precursor protein (APP) or amyloid beta (Aβ), or both. In some embodiments, more than one anti-Gal3 antibody or binding fragment thereof is administered to the subject.

[0280] As applied to any of the methods disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof is administered enterally, orally, intranasally, parenterally, intracranially, subcutaneously, intramuscularly, intradermally, or intravenously, or any combination thereof.

[0281] As applied to any of the methods disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to one or more peptides of SEQ ID NOs: 3-26. 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 belongs to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof competes with an antibody belonging to bin 3, 8, 17, or 24 for binding to Gal3.

[0282] As applied to any of the methods or uses disclosed herein, in some embodiments, an anti-Gal3 antibody or binding fragment thereof comprises any one or more sequences provided throughout the disclosure (e.g., V H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, V L -CDR3, heavy chain variable region, light chain variable region, heavy chain or light chain sequence). In some embodiments, the anti-Gal3 antibody or its binding fragment comprises Figure 18-32 any one or more sequences shown in , including any one or more CDRs, heavy chain variable regions, light chain variable regions, heavy chains, light chains, combinations of CDRs, combinations of variable regions, or combinations of heavy and light chains described herein. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a polypeptide comprising a heavy chain variable region, a heavy chain variable region, a light chain variable region, ... Figures 37-40 The peptide sequence encoded by any one or more of the nucleic acid sequences shown in (including any nucleic acid sequence encoding a heavy chain variable region, a light chain variable region, a heavy chain or a light chain) has a peptide sequence that is at least 80%, 85%, 90%, 95%, 99% or 100% homologous.

[0283] As applied to any of the methods disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises (1) a heavy chain variable region comprising V H -CDR1, V H -CDR2 and V H - CDR3, and (2) light chain variable region, which includes V L -CDR1, V L -CDR2 and V L -CDR3. In some embodiments, V H - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 27-44, 245-246, 588-615, V H - CDR2 comprises an amino acid sequence selected from SEQ ID NOs: 45-60, 247-248, 616-643, V H - CDR3 comprises an amino acid sequence selected from SEQ ID NO: 61-81, 249-250, 644-671, V L - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 82-101, 251-252, 672-699, V L - CDR2 comprises an amino acid sequence selected from SEQ ID NOs: 102-116, 253, 700-727 and V L- CDR3 comprises an amino acid sequence selected from SEQ ID NOs: 117-135, 254-255, 728-755. In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0284] As applied to any of the methods disclosed herein, in some embodiments, Figure 18 An exemplary V H -CDR1 sequence. In some embodiments, Figure 19 An exemplary V H -CDR2 sequence. In some embodiments, Figure 20 An exemplary V H -CDR3 sequence. In some embodiments, Figure 21 An exemplary V L -CDR1 sequence. In some embodiments, Figure 22 An exemplary V L -CDR2 sequence. In some embodiments, Figure 23 An exemplary V L - CDR3 sequence. In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0285] As applied to any of the methods disclosed herein, in some embodiments, the heavy chain variable region (V H ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 136-160, 256-257, 756-783. In some embodiments, the heavy chain variable region is selected from the group consisting of SEQ ID NOs: 136-160, 256-257, 756-783. In some embodiments, Figure 24 An exemplary V H In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0286] As applied to any of the methods disclosed herein, in some embodiments, the light chain variable region (V L) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 161-187, 258-259, 784-811. In some embodiments, the light chain variable region is selected from the group consisting of SEQ ID NOs: 161-187, 258-259, 784-811. In some embodiments, Figure 25 An exemplary V L In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0287] As applied to any of the methods disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: 1) V within SEQ ID NO: 136 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 161 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 2) V within SEQ ID NO: 137 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 162 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 3) V within SEQ ID NO: 138 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 163L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 4) V within SEQ ID NO: 139 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 164 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 5) V within SEQ ID NO: 140 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 165 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 6) V within SEQ ID NO: 141 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 166 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 7) V within SEQ ID NO: 142 H -CDR1, V H -CDR2, V H-V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 167 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 8) V within SEQ ID NO: 143 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 168 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 9) SEQ ID NO: 144 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 169 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 10) V within SEQ ID NO: 145 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 170 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, VL - CDR3; 11) V within SEQ ID NO:139 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:171 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 12) V within SEQ ID NO:146 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:172<​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 15) V within SEQ ID NO: 149 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 175 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 16) V within SEQ ID NO: 150 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 176 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 17) SEQ ID NO: 151 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 177 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 18) V within SEQ ID NO: 152 H -CDR1, V H -CDR2, V H -V of CDR3 H-CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 178 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 19) SEQ ID NO: 153 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 179 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 20) SEQ ID NO: 154 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 180 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 21) SEQ ID NO: 155 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 181 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L-CDR3; 22) V within SEQ ID NO:156 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:182 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 23) V within SEQ ID NO:157 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:183 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 24) V within SEQ ID NO:155[[ID=四十九]] H -CDR1, V H -CDR2, V H -V of CDR— H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:— L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 25) V within SEQ ID NO:158 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V[[ID=八十一]] H -CDR2, V H -CDR3 and V within SEQ ID NO:185 L -CDR1, V L It should be noted that there seems to be an incorrect "[[ID=四十九]]" in the original text which is maintained as is in the translation for the purpose of following the rules. You may want to double-check the accuracy of the original text.-CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 26) V within SEQ ID NO: 159 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 186 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 27) SEQ ID NO: 160 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 187 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 28) SEQ ID NO: 256 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 258 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 29) SEQ ID NO: 257 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, VH -CDR2, V H -CDR3 and V within SEQ ID NO: 259 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 30) SEQ ID NO: 756 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 784 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 31) SEQ ID NO: 757 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 785 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 32) SEQ ID NO: 758 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 786 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 33) SEQ ID NO: 759 VH -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 787 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 34) SEQ ID NO: 760 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 788 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 35) SEQ ID NO: 761 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 789 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 36) SEQ ID NO: 762 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 790 L -CDR1, V L -CDR2, V L-V of CDR3 L -V of CDR1 L -V of CDR2 L -V of CDR3; 37) V within SEQ ID NO:763 H -V of CDR1 H -V of CDR2 H -V of CDR3 H -V of CDR1 H -V of CDR2 H -V of CDR3 and V within SEQ ID NO:791 L -V of CDR1 L -V of CDR2 L -V of CDR3 L -V of CDR1 L -V of CDR2 L -V of CDR3; 38) V within SEQ ID NO:764 H -V of CDR1 H -V of CDR2 H -V of CDR3 H -V of CDR1 H -V of CDR2 H -V of CDR3 and V within SEQ ID NO:792 L -V of CDR1 L -V of CDR2 L -V of CDR3 L -V of CDR1 L -V of CDR2 L -V of CDR3; 39) V within SEQ ID NO:765 H [[ID=5​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​H -CDR3 and V within SEQ ID NO: 794 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 41) SEQ ID NO: 767 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 795 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 42) SEQ ID NO: 768 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 796 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 43) SEQ ID NO: 769 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 797 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 44) SEQ ID NO: 770 V H -CDR1, VH -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 798 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 45) SEQ ID NO: 771 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 799 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 46) SEQ ID NO: 772 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H - CDR3 and SEQ ID NO: 800 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 47) SEQ ID NO: 773 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 801 V L -CDR1, V L -CDR2, V L -V of CDR3 L-CDR1, V L -CDR2, V L -CDR3; 48) V within SEQ ID NO:774 H -CDR1, V H -CDR2, V H V of -CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:802 L -CDR1, V L -CDR2, V L V of -CDR3 L -CDR1, V L -CDR2, V L -CDR3; 49) V within SEQ ID NO:775 H -CDR1, V H -CDR2, V H V of -CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:803 L -CDR1, V L -CDR2, V L V of -CDR3 L -CDR1, V L -CDR2, V L -CDR3; 50) V within SEQ ID NO:776 H -CDR1, V H -CDR2, V H V of -CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:804 L -CDR1, V L -CDR2, V L V of -CDR3 L -CDR1, V L -CDR2, V L -CDR3; 51) V within SEQ ID NO:777 H -CDR1, V H -CDR2, V H V of -CDR3 H -CDR1, V H -CDR2, V H-CDR3 and SEQ ID NO: 805 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 52) SEQ ID NO: 778 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 806 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 53) SEQ ID NO: 779 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 807 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 54) SEQ ID NO: 780 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 808 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 55) SEQ ID NO: 781 V H -CDR1, VH -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 809 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 56) V within SEQ ID NO: 782 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 810 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; or 57) V within SEQ ID NO: 783 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 811 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3. In some embodiments, Figure 28 Exemplary combinations of heavy chain variable region CDRs are depicted in . In some embodiments, Figure 29 Exemplary combinations of light chain variable region CDRs are depicted in In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0288] As applied to any of the methods disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: 1) a heavy chain variable region of SEQ ID NO: 136 and a light chain variable region of SEQ ID NO: 161; 2) a heavy chain variable region of SEQ ID NO: 137 and a light chain variable region of SEQ ID NO: 162; 3) a heavy chain variable region of SEQ ID NO: 138 and a light chain variable region of SEQ ID NO: 163; 4) a heavy chain variable region of SEQ ID NO: 139 and a light chain variable region of SEQ ID NO: 164; 5) a heavy chain variable region of SEQ ID NO: 140 and a light chain variable region of SEQ ID NO: 165; 6) a heavy chain variable region of SEQ ID NO: 141 and a light chain variable region of SEQ ID NO: 166; 7) a heavy chain variable region of SEQ ID NO: 142 and a light chain variable region of SEQ ID NO: 167; 8) a heavy chain variable region of SEQ ID NO: 143 and a light chain variable region of SEQ ID NO: NO: 168; 9) the heavy chain variable region of SEQ ID NO: 144 and the light chain variable region of SEQ ID NO: 169; 10) the heavy chain variable region of SEQ ID NO: 145 and the light chain variable region of SEQ ID NO: 170; 11) the heavy chain variable region of SEQ ID NO: 139 and the light chain variable region of SEQ ID NO: 171; 12) the heavy chain variable region of SEQ ID NO: 146 and the light chain variable region of SEQ ID NO: 172; 13) the heavy chain variable region of SEQ ID NO: 147 and the light chain variable region of SEQ ID NO: 173; 14) the heavy chain variable region of SEQ ID NO: 148 and the light chain variable region of SEQ ID NO: 174; 15) the heavy chain variable region of SEQ ID NO: 149 and the light chain variable region of SEQ ID NO: 175; 16) the heavy chain variable region of SEQ ID NO: 150 and the light chain variable region of SEQ ID NO: 176; 17) 18) a heavy chain variable region of SEQ ID NO: 151 and a light chain variable region of SEQ ID NO: 177; 19) a heavy chain variable region of SEQ ID NO: 153 and a light chain variable region of SEQ ID NO: 179; 20) a heavy chain variable region of SEQ ID NO: 154 and a light chain variable region of SEQ ID NO: 180; 21) a heavy chain variable region of SEQ ID NO: 155 and a light chain variable region of SEQ ID NO: 181; 22) a heavy chain variable region of SEQ ID NO: 156 and a light chain variable region of SEQ ID NO: 182;23) the heavy chain variable region of SEQ ID NO: 157 and the light chain variable region of SEQ ID NO: 183; 24) the heavy chain variable region of SEQ ID NO: 155 and the light chain variable region of SEQ ID NO: 184; 25) the heavy chain variable region of SEQ ID NO: 158 and the light chain variable region of SEQ ID NO: 185; 26) the heavy chain variable region of SEQ ID NO: 159 and the light chain variable region of SEQ ID NO: 186; 27) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 187; 28) the heavy chain variable region of SEQ ID NO: 256 and the light chain variable region of SEQ ID NO: 258; 29) the heavy chain variable region of SEQ ID NO: 257 and the light chain variable region of SEQ ID NO: 259; 30) the heavy chain variable region of SEQ ID NO: 756 and the light chain variable region of SEQ ID NO: 784; 31) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 160; NO: 757 heavy chain variable region and SEQ ID NO: 785 light chain variable region; 32) SEQ ID NO: 758 heavy chain variable region and SEQ ID NO: 786 light chain variable region; 33) SEQ ID NO: 759 heavy chain variable region and SEQ ID NO: 787 light chain variable region; 34) SEQ ID NO: 760 heavy chain variable region and SEQ ID NO: 788 light chain variable region; 35) SEQ ID NO: 761 heavy chain variable region and SEQ ID NO: 789 light chain variable region; 36) SEQ ID NO: 762 heavy chain variable region and SEQ ID NO: 790 light chain variable region; 37) SEQ ID NO: 763 heavy chain variable region and SEQ ID NO: 791 light chain variable region; 38) SEQ ID NO: 764 heavy chain variable region and SEQ ID NO: 792 light chain variable region; 39) SEQ ID NO: 765 heavy chain variable region and SEQ ID NO: NO: 793; 40) the heavy chain variable region of SEQ ID NO: 766 and the light chain variable region of SEQ ID NO: 794; 41) the heavy chain variable region of SEQ ID NO: 767 and the light chain variable region of SEQ ID NO: 795; 42) the heavy chain variable region of SEQ ID NO: 768 and the light chain variable region of SEQ ID NO: 796; 43) the heavy chain variable region of SEQ ID NO: 769 and the light chain variable region of SEQ ID NO: 797; 44) the heavy chain variable region of SEQ ID NO: 770 and the light chain variable region of SEQ ID NO: 798; 45) the heavy chain variable region of SEQ ID NO: 771 and the light chain variable region of SEQ ID NO: 799;46) the heavy chain variable region of SEQ ID NO: 772 and the light chain variable region of SEQ ID NO: 800; 47) the heavy chain variable region of SEQ ID NO: 773 and the light chain variable region of SEQ ID NO: 801; 48) the heavy chain variable region of SEQ ID NO: 774 and the light chain variable region of SEQ ID NO: 802; 49) the heavy chain variable region of SEQ ID NO: 775 and the light chain variable region of SEQ ID NO: 803; 50) the heavy chain variable region of SEQ ID NO: 776 and the light chain variable region of SEQ ID NO: 804; 51) the heavy chain variable region of SEQ ID NO: 777 and the light chain variable region of SEQ ID NO: 805; 52) the heavy chain variable region of SEQ ID NO: 778 and the light chain variable region of SEQ ID NO: 806; 53) the heavy chain variable region of SEQ ID NO: 779 and the light chain variable region of SEQ ID NO: 807; 54) the heavy chain variable region of SEQ ID NO: 771 and the light chain variable region of SEQ ID NO: 808; 55) the heavy chain variable region of SEQ ID NO: 780 and the light chain variable region of SEQ ID NO: 808; 56) the heavy chain variable region of SEQ ID NO: 781 and the light chain variable region of SEQ ID NO: 809; 57) the heavy chain variable region of SEQ ID NO: 782 and the light chain variable region of SEQ ID NO: 810; or 58) the heavy chain variable region of SEQ ID NO: 783 and the light chain variable region of SEQ ID NO: 811. In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen-binding molecule that binds to Gal3.

[0289] As applied to any of the methods disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain (HC) sequence of any one of SEQ ID NOs: 188-216. In some embodiments, Figure 26 Exemplary HC sequences are depicted in 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.

[0290] As applied to any of the methods disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain (LC) sequence of any one of SEQ ID NOs: 217-243. Figure 27 Exemplary LC sequences are depicted in In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0291] As applied to any of the methods disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of at least one 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, F846C.1B2, F846C.1F5, F846C.1 H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F 847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 847.14H4, 846T.1H2, mIMT00 1. 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, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846 or a binding fragment thereof.As applied to any of the methods 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, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4 B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846.2D4, 846.2F11, 846T.10B1, 846T.2 E3, 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 or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from the group consisting of at least one of TB001, TB006, 19B5.2E6, 14H10.2C9, 15F10.2D6, 20H5.A3, 23H9.2E4, 2D10.2B2, 7D8.2D8, F846C.1B2, F846C.1F5, F846C.1H12, F846 C.2H3, F846TC.14E4, F846TC.16B5, F846TC.7F10, F849C.8D10, 846.4D5, 846T.4E11, 847.11D6, 847.20H7, 847.21B11, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F2, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody selected from 846.4D5, 15F10.2D6, F846C.1B2, and F846C.1H12. In some embodiments,. Figure 30The heavy and light chain CDRs associated with each of the aforementioned antibodies are depicted in . In some embodiments, Figure 31 The V associated with each of the aforementioned antibodies is depicted in H and V L In some embodiments, Figure 32 The HC and LC associated with each of the aforementioned antibodies are depicted in

[00145] In some embodiments, any of the methods disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0292] Also disclosed herein are uses of anti-Gal3 antibodies or binding fragments thereof for treating a neurodegenerative disease in a subject in need thereof. In some embodiments, the neurodegenerative disease comprises inflammation, encephalitis, Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, olfactory dysfunction, aphasia, Bell's palsy, transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease, fatal familial insomnia, epilepsy, spasticity, neurodevelopmental, Tourette syndrome, neuroinfectious disease, meningitis, encephalitis, mad cow disease, West Nile virus encephalitis, neuro-AIDS, fragile X syndrome, Guillain-Barré syndrome, brain metastasis, brain cancer, or any combination thereof. In some embodiments, the neurological disorder is Alzheimer's disease, and wherein the anti-Gal3 antibody or binding fragment thereof disrupts the binding between Gal3 and amyloid precursor protein (APP) or Aβ or both. In some embodiments, APP comprises the sequence of APP695 (SEQ ID NO: 2). In some embodiments, Aβ comprises Aβ monomers, Aβ oligomers, Aβ fibrils, or any combination thereof. In some embodiments, Aβ comprises the sequence of Aβ42 (SEQ ID NO: 244). In some embodiments, the anti-Gal3 antibody or its binding fragment reduces the binding between Gal3 and APP or Aβ or both by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% or any percentage within the range defined by any two of the above percentages. In some embodiments, the anti-Gal3 antibody or its binding fragment promotes the phagocytic function of the subject's microglia. In some embodiments, the anti-Gal3 antibody or its binding fragment inhibits Aβ-mediated activation of the subject's microglia. In some embodiments, Aβ-mediated activation of microglia is inhibited by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% or any percentage within a range defined by any two of the aforementioned percentages. In some embodiments, the anti-Gal3 antibody or its binding fragment inhibits Aβ fibril or oligomer formation in a subject. In some embodiments, Aβ fibril or oligomer formation is inhibited by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% or any percentage within a range defined by any two of the aforementioned percentages. In some embodiments, the anti-Gal3 antibody or its binding fragment disrupts the interaction between Gal3 and Toll-like receptor 4 (TLR4) or triggering receptor 2 on myeloid cells (TREM2) or both.In some embodiments, the interaction between Gal3 and TLR4 or TREM2 or both is disrupted by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%, or any percentage within a range bounded by any two of the foregoing percentages.

[0293] Also disclosed herein is the use of an anti-Gal3 antibody or a binding fragment thereof in treating a primary disease in a subject in need thereof. In some embodiments, the primary disease comprises Alzheimer's disease, cerebral beta-amyloid angiopathy, glaucoma, retinal ganglion cell degeneration, Parkinson's disease, Lewy dementia, multiple system atrophy, synucleinopathy, Pick's disease, cortical basal degeneration, tauopathy, frontotemporal lobar degeneration, Huntington's disease, dentate-rubral-pallidular Lewy body atrophy, spinal bulbar muscular atrophy, spinocerebellar ataxia, fragile X syndrome, Baratela-Scott syndrome, Friedreich's ataxia, myotonic dystrophy, Alexander disease, familial British dementia, familial Danish dementia, Peyer's disease, and other neurological disorders. syphilis, seipin disease, AA (secondary) amyloidosis, type II diabetes mellitus, fibrinogen amyloidosis, dialysis amyloidosis, inclusion body myositis / myopathy, familial amyloidosis neuropathy, senile systemic amyloidosis, serpentine lesions, cardiac atrial amyloidosis, pituitary prolactinoma, insulin amyloidosis, corneal lactoferrin amyloidosis, pulmonary alveolar proteinosis, seminal vesicle amyloidosis, cutaneous lichen amyloidosis, Mallory bodies or odontogenic (Pindborg) tumor amyloid or any disease caused by misfolding or aggregation of proteins, or any combination thereof.

[0294] Also disclosed herein is the use of an anti-Gal3 antibody or its binding fragment in promoting neuronal regeneration in a subject in need thereof. In some embodiments, the subject comprises a neuronal degeneration associated with inflammation, encephalitis, Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, olfactory dysfunction, aphasia, Bell's palsy, transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease, fatal familial insomnia, epilepsy, spasticity, neurodevelopmental disease, Tourette syndrome, neuroinfectious disease, meningitis, encephalitis, mad cow disease, West Nile virus encephalitis, neuro-AIDS, fragile X syndrome, Guillain-Barré syndrome, brain metastasis, brain cancer, or any combination thereof. In some embodiments, the neuronal degeneration is associated with Alzheimer's disease, and wherein the anti-Gal3 antibody or its binding fragment disrupts the binding between Gal3 and amyloid precursor protein (APP) or amyloid beta (Aβ) or the two in the subject. In some embodiments, more than one anti-Gal3 antibody or binding fragment thereof is administered to a subject.

[0295] As applied to any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to one or more peptides of SEQ ID NOs: 3-26. 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 belongs to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof competes with an antibody belonging to bin 3, 8, 17, or 24 for binding to Gal3.

[0296] As used in any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises (1) a heavy chain variable region comprising V H -CDR1, V H -CDR2 and V H - CDR3, and (2) light chain variable region, which includes V L -CDR1, V L -CDR2 and V L -CDR3. In some embodiments, V H - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 27-44, 245-246, 588-615, V H - CDR2 comprises an amino acid sequence selected from SEQ ID NOs: 45-60, 247-248, 616-643, V H - CDR3 comprises an amino acid sequence selected from SEQ ID NO: 61-81, 249-250, 644-671, V L - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 82-101, 251-252, 672-699, V L - CDR2 comprises an amino acid sequence selected from SEQ ID NOs: 102-116, 253, 700-727 and V L - CDR3 comprises an amino acid sequence selected from SEQ ID NOs: 117-135, 254-255, 728-755. In some embodiments, any use disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0297] As applied to any of the uses disclosed herein, in some embodiments, Figure 18 An exemplary V H -CDR1 sequence. In some embodiments, Figure 19 An exemplary V H -CDR2 sequence. In some embodiments, Figure 20 An exemplary V H -CDR3 sequence. In some embodiments, Figure 21 An exemplary V L -CDR1 sequence. In some embodiments, Figure 22 An exemplary V L -CDR2 sequence. In some embodiments, Figure 23 An exemplary V L - CDR3 sequence. In some embodiments, any use disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed with an antigen binding molecule that binds to Gal3.

[0298] As applied to any of the uses disclosed herein, in some embodiments, the heavy chain variable region (V H ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 136-160, 256-257, 756-783. In some embodiments, the heavy chain variable region is selected from the group consisting of SEQ ID NOs: 136-160, 256-257, 756-783. In some embodiments, Figure 24 An exemplary V H In some embodiments, any of the uses disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0299] As applied to any of the uses disclosed herein, in some embodiments, the light chain variable region (V L ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 161-187, 258-259, 784-811. In some embodiments, the light chain variable region is selected from the group consisting of SEQ ID NOs: 161-187, 258-259, 784-811. In some embodiments, Figure 25 An exemplary V L In some embodiments, any of the uses disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3.

[0300] As used in any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: 1) V within SEQ ID NO: 136 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 161 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 2) V within SEQ ID NO: 137 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 162 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 3) V within SEQ ID NO: 138 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 163 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 4) V within SEQ ID NO: 139 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H-CDR3 and SEQ ID NO: 164 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 5) V within SEQ ID NO: 140 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 165 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 6) V within SEQ ID NO: 141 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 166 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 7) V within SEQ ID NO: 142 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 167 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 8) V within SEQ ID NO: 143 H -CDR1, V H-CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:168 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 9) V within SEQ ID NO:144 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:169 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 10) V within SEQ ID NO:145 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V[[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​L -CDR2, V L -CDR3; 12) V within SEQ ID NO: 146 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 172 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 13) V within SEQ ID NO: 147 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 173 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 14) V within SEQ ID NO: 148 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 174 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 15) V within SEQ ID NO: 149 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H-CDR3 and V within SEQ ID NO: 175 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 16) V within SEQ ID NO: 150 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 176 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 17) SEQ ID NO: 151 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 177 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 18) V within SEQ ID NO: 152 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 178 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 19) SEQ ID NO: 153 V H -CDR1, V H-CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 179 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 20) SEQ ID NO: 154 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 180 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 21) SEQ ID NO: 155 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 181 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 22) SEQ ID NO: 156 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 182 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, VL - CDR2, V L - CDR3; 23) V within SEQ ID NO:157 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:183 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 24) V within SEQ ID NO:155 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:184 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 25) V within SEQ ID NO:158 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:185 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 26) V within SEQ ID NO:159 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:186L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 27) SEQ ID NO: 160 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 187 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 28) SEQ ID NO: 256 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 258 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 29) SEQ ID NO: 257 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 259 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 30) SEQ ID NO: 756 V H -CDR1, V H -CDR2, V H-V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 784 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 31) SEQ ID NO: 757 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 785 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 32) SEQ ID NO: 758 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 786 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 33) SEQ ID NO: 759 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 787 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, VL - CDR3; 34) V within SEQ ID NO:760 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:788 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 35) V within SEQ ID NO:761 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:789 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V[[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 38) SEQ ID NO: 764 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 792 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 39) SEQ ID NO: 765 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 793 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 40) SEQ ID NO: 766 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 794 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 41) SEQ ID NO: 767 V H -CDR1, V H -CDR2, V H -V of CDR3 H-CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 795 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 42) SEQ ID NO: 768 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 796 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 43) SEQ ID NO: 769 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 797 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 44) SEQ ID NO: 770 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 798 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L-CDR3; 45) SEQ ID NO: 771 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 799 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 46) SEQ ID NO: 772 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H - CDR3 and SEQ ID NO: 800 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 47) SEQ ID NO: 773 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 801 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 48) SEQ ID NO: 774 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 802 L -CDR1, VL -V of CDR2, L -V of CDR3 L -V of CDR1, L -V of CDR2, L -V of CDR3; 49) V within SEQ ID NO:775 H -V of CDR1, H -V of CDR2, H -V of CDR3 H -V of CDR1, H -V of CDR2, <00(02779>-V of CDR3 and V within SEQ ID NO:803 L -V of CDR1, L -V of CDR2, L -V of CDR3 L -V of CDR1, L -V of CDR2, L -V of CDR3; 50) V within SEQ ID NO:776 H -V of CDR1, H -V of CDR2, H -V of CDR3 H -V of CDR1, H -V of CDR2, H -V of CDR3 and V within SEQ ID NO:804 L -V of CDR1, L -V of CDR2, L -V of CDR3 L -V of CDR1, L -V of CDR2, L -V of CDR3; 51) V within SEQ ID NO:777 H -V of CDR1, H -V of CDR2, <000(02800>-V of CDR3 H -V of CDR1, H -V of CDR2, H -V of CDR)3 and V within SEQ ID NO:805 L -V of CDR1, L -V of CDR2, L -V of CDR3 L -V of CDR1, L -V of CDR2, L -V of CDR3; 52) V within SEQ ID NO:778 H -V of CDR1, H -V of CDR2, H -V of CDR3 H-CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 806 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 53) SEQ ID NO: 779 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 807 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 54) SEQ ID NO: 780 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 808 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 55) SEQ ID NO: 781 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 809 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L-CDR3; 56) V within SEQ ID NO: 782 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 810 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; or 57) V within SEQ ID NO: 783 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 811 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3. In some embodiments, Figure 28 Exemplary combinations of heavy chain variable region CDRs are depicted in . In some embodiments, Figure 29 Exemplary combinations of light chain variable region CDRs are depicted in In some embodiments, any of the uses disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed with an antigen binding molecule that binds to Gal3.

[0301] As used in any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: 1) a heavy chain variable region of SEQ ID NO: 136 and a light chain variable region of SEQ ID NO: 161; 2) a heavy chain variable region of SEQ ID NO: 137 and a light chain variable region of SEQ ID NO: 162; 3) a heavy chain variable region of SEQ ID NO: 138 and a light chain variable region of SEQ ID NO: 163; 4) a heavy chain variable region of SEQ ID NO: 139 and a light chain variable region of SEQ ID NO: 164; 5) a heavy chain variable region of SEQ ID NO: 140 and a light chain variable region of SEQ ID NO: 165; 6) a heavy chain variable region of SEQ ID NO: 141 and a light chain variable region of SEQ ID NO: 166; 7) a heavy chain variable region of SEQ ID NO: 142 and a light chain variable region of SEQ ID NO: 167; 8) a heavy chain variable region of SEQ ID NO: 143 and a light chain variable region of SEQ ID NO: NO: 168; 9) the heavy chain variable region of SEQ ID NO: 144 and the light chain variable region of SEQ ID NO: 169; 10) the heavy chain variable region of SEQ ID NO: 145 and the light chain variable region of SEQ ID NO: 170; 11) the heavy chain variable region of SEQ ID NO: 139 and the light chain variable region of SEQ ID NO: 171; 12) the heavy chain variable region of SEQ ID NO: 146 and the light chain variable region of SEQ ID NO: 172; 13) the heavy chain variable region of SEQ ID NO: 147 and the light chain variable region of SEQ ID NO: 173; 14) the heavy chain variable region of SEQ ID NO: 148 and the light chain variable region of SEQ ID NO: 174; 15) the heavy chain variable region of SEQ ID NO: 149 and the light chain variable region of SEQ ID NO: 175; 16) the heavy chain variable region of SEQ ID NO: 150 and the light chain variable region of SEQ ID NO: 176; 17) 18) a heavy chain variable region of SEQ ID NO: 151 and a light chain variable region of SEQ ID NO: 177; 19) a heavy chain variable region of SEQ ID NO: 153 and a light chain variable region of SEQ ID NO: 179; 20) a heavy chain variable region of SEQ ID NO: 154 and a light chain variable region of SEQ ID NO: 180; 21) a heavy chain variable region of SEQ ID NO: 155 and a light chain variable region of SEQ ID NO: 181; 22) a heavy chain variable region of SEQ ID NO: 156 and a light chain variable region of SEQ ID NO: 182;23) the heavy chain variable region of SEQ ID NO: 157 and the light chain variable region of SEQ ID NO: 183; 24) the heavy chain variable region of SEQ ID NO: 155 and the light chain variable region of SEQ ID NO: 184; 25) the heavy chain variable region of SEQ ID NO: 158 and the light chain variable region of SEQ ID NO: 185; 26) the heavy chain variable region of SEQ ID NO: 159 and the light chain variable region of SEQ ID NO: 186; 27) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 187; 28) the heavy chain variable region of SEQ ID NO: 256 and the light chain variable region of SEQ ID NO: 258; 29) the heavy chain variable region of SEQ ID NO: 257 and the light chain variable region of SEQ ID NO: 259; 30) the heavy chain variable region of SEQ ID NO: 756 and the light chain variable region of SEQ ID NO: 784; 31) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 160; NO: 757 heavy chain variable region and SEQ ID NO: 785 light chain variable region; 32) SEQ ID NO: 758 heavy chain variable region and SEQ ID NO: 786 light chain variable region; 33) SEQ ID NO: 759 heavy chain variable region and SEQ ID NO: 787 light chain variable region; 34) SEQ ID NO: 760 heavy chain variable region and SEQ ID NO: 788 light chain variable region; 35) SEQ ID NO: 761 heavy chain variable region and SEQ ID NO: 789 light chain variable region; 36) SEQ ID NO: 762 heavy chain variable region and SEQ ID NO: 790 light chain variable region; 37) SEQ ID NO: 763 heavy chain variable region and SEQ ID NO: 791 light chain variable region; 38) SEQ ID NO: 764 heavy chain variable region and SEQ ID NO: 792 light chain variable region; 39) SEQ ID NO: 765 heavy chain variable region and SEQ ID NO: NO: 793; 40) the heavy chain variable region of SEQ ID NO: 766 and the light chain variable region of SEQ ID NO: 794; 41) the heavy chain variable region of SEQ ID NO: 767 and the light chain variable region of SEQ ID NO: 795; 42) the heavy chain variable region of SEQ ID NO: 768 and the light chain variable region of SEQ ID NO: 796; 43) the heavy chain variable region of SEQ ID NO: 769 and the light chain variable region of SEQ ID NO: 797; 44) the heavy chain variable region of SEQ ID NO: 770 and the light chain variable region of SEQ ID NO: 798; 45) the heavy chain variable region of SEQ ID NO: 771 and the light chain variable region of SEQ ID NO: 799;46) the heavy chain variable region of SEQ ID NO: 772 and the light chain variable region of SEQ ID NO: 800; 47) the heavy chain variable region of SEQ ID NO: 773 and the light chain variable region of SEQ ID NO: 801; 48) the heavy chain variable region of SEQ ID NO: 774 and the light chain variable region of SEQ ID NO: 802; 49) the heavy chain variable region of SEQ ID NO: 775 and the light chain variable region of SEQ ID NO: 803; 50) the heavy chain variable region of SEQ ID NO: 776 and the light chain variable region of SEQ ID NO: 804; 51) the heavy chain variable region of SEQ ID NO: 777 and the light chain variable region of SEQ ID NO: 805; 52) the heavy chain variable region of SEQ ID NO: 778 and the light chain variable region of SEQ ID NO: 806; 53) the heavy chain variable region of SEQ ID NO: 779 and the light chain variable region of SEQ ID NO: 807; 54) the heavy chain variable region of SEQ ID NO: 771 and the light chain variable region of SEQ ID NO: 808; 55) a heavy chain variable region of SEQ ID NO: 780 and a light chain variable region of SEQ ID NO: 808; 56) a heavy chain variable region of SEQ ID NO: 781 and a light chain variable region of SEQ ID NO: 809; 57) a heavy chain variable region of SEQ ID NO: 782 and a light chain variable region of SEQ ID NO: 810; or 58) a heavy chain variable region of SEQ ID NO: 783 and a light chain variable region of SEQ ID NO: 811. In some embodiments, any use disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed using an antigen binding molecule that binds to Gal3. In some embodiments, the antibody has a sequence that is a consensus sequence of 1, 2, 3, 4, 5, or 6 CDRs of any two or more (e.g., 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, or all) antibodies provided herein. In some embodiments, the antibody has a sequence that is a consensus sequence of the VH, VL, or VH and VL of any two or more (e.g., 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, or all) antibodies provided herein.

[0302] As used in any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain (HC) sequence of any one of SEQ ID NOs: 188-216. In some embodiments, Figure 26 Exemplary HC sequences are depicted in In some embodiments, any of the uses disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed with an antigen binding molecule that binds to Gal3.

[0303] As used in any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain (LC) sequence of any one of SEQ ID NOs: 217-243. Figure 27 Exemplary LC sequences are depicted in In some embodiments, any of the uses disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed with an antigen binding molecule that binds to Gal3.

[0304] 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 at least one 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, F846C.1B2, F846C.1F5, F846C.1 H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F 847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 847.14H4, 846T.1H2, mIMT00 1. 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, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846 or a binding fragment thereof.As used in any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or its binding fragment is selected from TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4 B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846.2D4, 846.2F11, 846T.10B1, 846T.2 E3, 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 or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or its binding fragment is selected from TB001, TB006, 19B5.2E6, 14H10.2C9, 15F10.2D6, 20H5.A3, 23H9.2E4, 2D10.2B2, 7D8.2D8, F846C.1B2, F846C.1F5, F846C.1H12, F846C.2H3, F846 TC.14E4, F846TC.16B5, F846TC.7F10, F849C.8D10, 846.4D5, 846T.4E11, 847.11D6, 847.20H7, 847.21B11, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F2, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody selected from 846.4D5, 15F10.2D6, F846C.1B2, and F846C.1H12. In some embodiments,. Figure 30The heavy and light chain CDRs associated with each of the aforementioned antibodies are depicted in FIG. Figure 31 The V associated with each of the aforementioned antibodies is depicted in H and V L In some embodiments, Figure 32 The HC and LC associated with each of the aforementioned antibodies are depicted in In some embodiments, any of the uses disclosed herein involving anti-Gal3 antibodies or binding fragments can be performed with an antigen binding molecule that binds to Gal3.

[0305] As used in any of the uses disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof is administered enterally, orally, intranasally, parenterally, intracranially, subcutaneously, intramuscularly, intradermally, or intravenously, or any combination thereof. In some embodiments, the subject is a mammal. In some cases, the subject is a human. Directions for use - Blood-brain barrier penetrability

[0306] In some embodiments, any of the anti-Gal3 antibodies or binding fragments thereof disclosed herein are capable of passing through the blood-brain barrier and / or the blood-spinal cord barrier. In some embodiments, this phenomenon can be utilized by conjugating any of the anti-Gal3 antibodies or binding fragments thereof that can pass through the blood-brain barrier and / or the blood-spinal cord barrier to a payload to prepare an antibody conjugate. The blood-brain barrier and / or the blood-spinal cord barrier in these embodiments can be the blood-brain barrier and / or the blood-spinal cord barrier of mammals such as mice, rats, other rodents, cats, dogs, rabbits, cattle, horses, sheep, pigs, goats or humans. In some examples, the payload may not be able to pass through the blood-brain barrier and / or the blood-spinal cord barrier normally, or may not be able to pass through it effectively. For example, the payload can be used, for example, to have a cytotoxic effect on cancer cells, to treat diseases, or for diagnosis or detection. In addition to the payloads disclosed herein, any other payload conventionally known in the art can be conjugated to any of the anti-Gal3 antibodies or binding fragments thereof disclosed herein.

[0307] Disclosed herein are antibody conjugates comprising any one of an anti-Gal3 antibody or a binding fragment thereof and a payload conjugated to the anti-Gal3 antibody or its binding fragment, wherein the antibody conjugate is capable of crossing the blood-brain barrier. In some embodiments, the payload is unable to independently cross the blood-brain barrier or has low permeability across the blood-brain barrier when not conjugated to an anti-Gal3 antibody or its binding fragment. In some embodiments, the barrier is located in a subject whose blood-brain barrier is weakened or altered due to a disease that affects the blood-brain barrier (e.g., reduces the structural integrity of the blood-brain barrier).

[0308] In some embodiments, conjugation of a cargo to an anti-Gal3 antibody or binding fragment thereof increases the permeability of the cargo across the blood-brain barrier by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, or 500%, or any percentage within a range defined by any two of the foregoing percentages, compared to unconjugated cargo. In some embodiments, the permeability of the cargo across the blood-brain barrier is less than 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the permeability of the antibody conjugate across the blood-brain barrier. In some embodiments, the cargo or the anti-Gal3 antibody or binding fragment thereof, or both, are used to treat neurological disorders. In some embodiments, the neurological disorder comprises inflammation, encephalitis, Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, olfactory dysfunction, aphasia, Bell's palsy, transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease, fatal familial insomnia, epilepsy, spasticity, neurodevelopmental, Tourette syndrome, neuroinfectious disease, meningitis, encephalitis, mad cow disease, West Nile virus encephalitis, neuro-AIDS, fragile X syndrome, Guillain-Barré syndrome, brain metastasis or brain cancer (primary or secondary brain tumor) or any combination thereof. In some embodiments, the payload is a cytotoxic payload, a microtubule disrupting agent, a DNA modifying agent, an Akt inhibitor, a polymerase inhibitor, a detectable moiety, an immunomodulatory agent, an immune modulator, an immunotoxin, a nucleic acid polymer, an aptamer, a peptide, a protein, an enzyme or any combination thereof. In some embodiments, the payload is a second antibody. In some embodiments, the second antibody is incapable of independently crossing the blood-brain barrier or has low permeability across the blood-brain barrier when not conjugated to an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the blood-brain barrier is a mammalian blood-brain barrier. In some embodiments, the blood-brain barrier is a human blood-brain barrier. In some embodiments, the antibody conjugate is formulated for enteral, oral, intranasal, parenteral, intracranial, subcutaneous, intramuscular, intradermal, or intravenous administration, or any combination thereof.

[0309] As applied to any of the antibody conjugates, in some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to one or more peptides of SEQ ID NOs: 3-26. 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 belongs to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the interaction is disrupted by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99%, or any percentage within a range bounded by any two of the aforementioned percentages. In some embodiments, the anti-Gal3 antibody or binding fragment thereof competes with an antibody belonging to bin 3, 8, 17, or 24 for binding to Gal3.

[0310] As applied to any antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises any one or more sequences provided throughout the disclosure (e.g., V H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, V L -CDR3, heavy chain variable region, light chain variable region, heavy chain or light chain sequence). In some embodiments, the anti-Gal3 antibody or its binding fragment comprises Figure 18-32 any one or more sequences shown in , including any one or more CDRs, heavy chain variable regions, light chain variable regions, heavy chains, light chains, combinations of CDRs, combinations of variable regions, or combinations of heavy and light chains described herein. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a polypeptide comprising a heavy chain variable region, a heavy chain variable region, a light chain variable region, ... Figures 37-40 The peptide sequence encoded by any one or more of the nucleic acid sequences shown in (including any nucleic acid sequence encoding a heavy chain variable region, a light chain variable region, a heavy chain or a light chain) has a peptide sequence that is at least 80%, 85%, 90%, 95%, 99% or 100% homologous.

[0311] As applied to any antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises (1) a heavy chain variable region comprising V H -CDR1, V H -CDR2 and V H - CDR3, and (2) light chain variable region, which includes V L -CDR1, V L-CDR2 and V L -CDR3. In some embodiments, V H - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 27-44, 245-246, 588-615, V H - CDR2 comprises an amino acid sequence selected from SEQ ID NOs: 45-60, 247-248, 616-643, V H - CDR3 comprises an amino acid sequence selected from SEQ ID NO: 61-81, 249-250, 644-671, V L - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 82-101, 251-252, 672-699, V L - CDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 102-116, 253, 700-727, and V L - CDR3 comprises an amino acid sequence selected from SEQ ID NO: 117-135, 254-255, 728-755.

[0312] As applied to any antibody conjugate, in some embodiments, Figure 18 An exemplary V H -CDR1 sequence. In some embodiments, Figure 19 An exemplary V H -CDR2 sequence. In some embodiments, Figure 20 An exemplary V H -CDR3 sequence. In some embodiments, Figure 21 An exemplary V L -CDR1 sequence. In some embodiments, Figure 22 An exemplary V L -CDR2 sequence. In some embodiments, Figure 23 An exemplary V L -CDR3 sequence.

[0313] As applied to any antibody conjugate, in some embodiments, the heavy chain variable region (V H ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 136-160, 256-257. In some embodiments, the heavy chain variable region is selected from the group consisting of SEQ ID NOs: 136-160, 256-257. In some embodiments, Figure 24 An exemplary V H .

[0314] As applied to any antibody conjugate, in some embodiments, the light chain variable region (V L ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 161-187, 258-259. In some embodiments, the light chain variable region is selected from the group consisting of SEQ ID NOs: 161-187, 258-259. In some embodiments, Figure 25 An exemplary V L .

[0315] As applied to any antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: 1) V within SEQ ID NO: 136 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 161 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 2) V within SEQ ID NO: 137 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 162 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 3) V within SEQ ID NO: 138 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 163 L -CDR1, VL -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 4) V within SEQ ID NO: 139 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 164 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 5) V within SEQ ID NO: 140 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 165 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 6) V within SEQ ID NO: 141 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 166 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 7) V within SEQ ID NO: 142 H -CDR1, V H -CDR2, V H -V of CDR3 H-CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 167 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 8) V within SEQ ID NO: 143 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 168 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 9) SEQ ID NO: 144 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 169 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 10) V within SEQ ID NO: 145 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 170 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L-CDR3; 11) V within SEQ ID NO: 139 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 171 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 12) V within SEQ ID NO: 146 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 172 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 13) V within SEQ ID NO: 147 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 173 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 14) V within SEQ ID NO: 148 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 174 L -CDR1, V L-CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 15) V within SEQ ID NO: 149 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 175 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 16) V within SEQ ID NO: 150 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 176 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 17) SEQ ID NO: 151 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 177 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 18) V within SEQ ID NO: 152 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, VH - CDR2, V H - CDR3 and V within SEQ ID NO:178 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 19) V within SEQ ID NO:153 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:179 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 20) V within SEQ ID NO:154 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:180 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 21) V within SEQ ID NO:155 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:181 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 22) V within SEQ ID NO:156H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 182 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 23) SEQ ID NO: 157 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 183 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 24) SEQ ID NO: 155 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 184 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 25) V within SEQ ID NO: 158 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 185 L -CDR1, V L -CDR2, V L-V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 26) V within SEQ ID NO: 159 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 186 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 27) SEQ ID NO: 160 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 187 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 28) SEQ ID NO: 256 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 258 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 29) SEQ ID NO: 257 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, VH -V within CDR3 and SEQ ID NO:259 L -V of CDR1 L -V of CDR2 L -V of CDR3 L -V of CDR1 L -V of CDR2 L -V of CDR3; 30) V within SEQ ID NO:756 H -V of CDR1 H -V of CDR2 H -V of CDR3 H -V of CDR1 H -V of CDR2 H -V within CDR3 and SEQ ID NO:784 L -V of CDR1 L -V of CDR2 L -V of CDR3 L -V of CDR1 L -V of CDR2 L -V of CDR3; 31) V within SEQ ID NO:757 H -V of CDR1 H -V of CDR2 H -V of CDR上3 H -V of CDR1 H -V of CDR2 H -V within CDR3 and SEQ ID NO:785 L -V of CDR1 L -V of CDR2 L -V of CDR3 L -V of CDR1 L -V of CDR2 L -V of CDR3; 32) V within SEQ ID NO:758 H -V of CDR1 H -V of CDR2 H -V of CDR3 H -V of CDR1 H -V of CDR2 H -V within CDR3 and SEQ ID NO:786 L -V of CDR1 L -V of CDR2<00,03292>-V of CDR3 L -V off CDR1 L -V of CDR2 L -V of CDR3; 33) V within SEQ ID NO:759 H -V of CDR1H -V of CDR2 H -V of CDR3 H -V of CDR1 H -V of CDR2 H -V in CDR3 and SEQ ID NO:787 L -V of CDR1 L -V of CDR2 L -V of CDR3 L -V of CDR1 L -V of CDR2 L -V of CDR3; 34) V in SEQ ID NO:760 H -V of CDR1 H -V of CDR2 H -V of CDR3 H -V of CDR1 H -V of CDR2 H -V in CDR3 and SEQ ID NO:788 L -V of CDR1 L -V of CDR2[[ID=)38]] L -V of CDR3 L -V of CDR1 L -V of CDR2 L -V of CDR3; 35) V in SEQ ID NO:761 H -V of CDR1<00033?21>-V of CDR2 H -V of CDR3 H -V of CDR1 H -V of CDR2 H -V in CDR3 and SEQ ID NO:789 L -V of CDR1 L -V of CDR2 L -V of CDR3 L -V of CDR1 L -V of CDR2 L [[ID=6)9]]-V of CDR3; 36) V in SEQ ID NO:762 H -V of CDR1 H )]]END]]-V of CDR2 H -V of CDR3 H -V of CDR1 H -V of CDR2<00033?37>-V in CDR3 and SEQ ID NO:790 L -V of CDR1 L -V of CDR2 L -V of CDR3 L-CDR1, V L -CDR2, V L -CDR3; 37) SEQ ID NO: 763 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 791 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 38) SEQ ID NO: 764 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 792 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 39) SEQ ID NO: 765 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 793 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 40) SEQ ID NO: 766 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H-CDR3 and V within SEQ ID NO: 794 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 41) SEQ ID NO: 767 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 795 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 42) SEQ ID NO: 768 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 796 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 43) SEQ ID NO: 769 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 797 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 44) SEQ ID NO: 770 V H -CDR1, VH - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:798 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 45) V within SEQ ID NO:771 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:799 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 46) V within SEQ ID NO:772 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:800 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 47) V within SEQ ID NO:773 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:801 L - CDR1, V L - CDR2, V L - V of CDR3 L-CDR1, V L -CDR2, V L -CDR3; 48) SEQ ID NO: 774 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 802 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 49) SEQ ID NO: 775 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 803 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 50) SEQ ID NO: 776 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 804 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 51) SEQ ID NO: 777 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H-CDR3 and SEQ ID NO: 805 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 52) SEQ ID NO: 778 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 806 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 53) SEQ ID NO: 779 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 807 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 54) SEQ ID NO: 780 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 808 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 55) SEQ ID NO: 781 V H -CDR1, V H-CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 809 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 56) V within SEQ ID NO: 782 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 810 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; or 57) V within SEQ ID NO: 783 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 811 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3. In some embodiments, Figure 28 Exemplary combinations of heavy chain variable region CDRs are depicted in . In some embodiments, Figure 29 Exemplary combinations of light chain variable region CDRs are depicted in .

[0316] As applied to any antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: 1) a heavy chain variable region of SEQ ID NO: 136 and a light chain variable region of SEQ ID NO: 161; 2) a heavy chain variable region of SEQ ID NO: 137 and a light chain variable region of SEQ ID NO: 162; 3) a heavy chain variable region of SEQ ID NO: 138 and a light chain variable region of SEQ ID NO: 163; 4) a heavy chain variable region of SEQ ID NO: 139 and a light chain variable region of SEQ ID NO: 164; 5) a heavy chain variable region of SEQ ID NO: 140 and a light chain variable region of SEQ ID NO: 165; 6) a heavy chain variable region of SEQ ID NO: 141 and a light chain variable region of SEQ ID NO: 166; 7) a heavy chain variable region of SEQ ID NO: 142 and a light chain variable region of SEQ ID NO: 167; 8) a heavy chain variable region of SEQ ID NO: 143 and a light chain variable region of SEQ ID NO: NO: 168; 9) the heavy chain variable region of SEQ ID NO: 144 and the light chain variable region of SEQ ID NO: 169; 10) the heavy chain variable region of SEQ ID NO: 145 and the light chain variable region of SEQ ID NO: 170; 11) the heavy chain variable region of SEQ ID NO: 139 and the light chain variable region of SEQ ID NO: 171; 12) the heavy chain variable region of SEQ ID NO: 146 and the light chain variable region of SEQ ID NO: 172; 13) the heavy chain variable region of SEQ ID NO: 147 and the light chain variable region of SEQ ID NO: 173; 14) the heavy chain variable region of SEQ ID NO: 148 and the light chain variable region of SEQ ID NO: 174; 15) the heavy chain variable region of SEQ ID NO: 149 and the light chain variable region of SEQ ID NO: 175; 16) the heavy chain variable region of SEQ ID NO: 150 and the light chain variable region of SEQ ID NO: 176; 17) 18) a heavy chain variable region of SEQ ID NO: 151 and a light chain variable region of SEQ ID NO: 177; 19) a heavy chain variable region of SEQ ID NO: 153 and a light chain variable region of SEQ ID NO: 179; 20) a heavy chain variable region of SEQ ID NO: 154 and a light chain variable region of SEQ ID NO: 180; 21) a heavy chain variable region of SEQ ID NO: 155 and a light chain variable region of SEQ ID NO: 181; 22) a heavy chain variable region of SEQ ID NO: 156 and a light chain variable region of SEQ ID NO: 182;23) the heavy chain variable region of SEQ ID NO: 157 and the light chain variable region of SEQ ID NO: 183; 24) the heavy chain variable region of SEQ ID NO: 155 and the light chain variable region of SEQ ID NO: 184; 25) the heavy chain variable region of SEQ ID NO: 158 and the light chain variable region of SEQ ID NO: 185; 26) the heavy chain variable region of SEQ ID NO: 159 and the light chain variable region of SEQ ID NO: 186; 27) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 187; 28) the heavy chain variable region of SEQ ID NO: 256 and the light chain variable region of SEQ ID NO: 258; 29) the heavy chain variable region of SEQ ID NO: 257 and the light chain variable region of SEQ ID NO: 259; 30) the heavy chain variable region of SEQ ID NO: 756 and the light chain variable region of SEQ ID NO: 784; 31) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 160; NO: 757 heavy chain variable region and SEQ ID NO: 785 light chain variable region; 32) SEQ ID NO: 758 heavy chain variable region and SEQ ID NO: 786 light chain variable region; 33) SEQ ID NO: 759 heavy chain variable region and SEQ ID NO: 787 light chain variable region; 34) SEQ ID NO: 760 heavy chain variable region and SEQ ID NO: 788 light chain variable region; 35) SEQ ID NO: 761 heavy chain variable region and SEQ ID NO: 789 light chain variable region; 36) SEQ ID NO: 762 heavy chain variable region and SEQ ID NO: 790 light chain variable region; 37) SEQ ID NO: 763 heavy chain variable region and SEQ ID NO: 791 light chain variable region; 38) SEQ ID NO: 764 heavy chain variable region and SEQ ID NO: 792 light chain variable region; 39) SEQ ID NO: 765 heavy chain variable region and SEQ ID NO: NO: 793; 40) the heavy chain variable region of SEQ ID NO: 766 and the light chain variable region of SEQ ID NO: 794; 41) the heavy chain variable region of SEQ ID NO: 767 and the light chain variable region of SEQ ID NO: 795; 42) the heavy chain variable region of SEQ ID NO: 768 and the light chain variable region of SEQ ID NO: 796; 43) the heavy chain variable region of SEQ ID NO: 769 and the light chain variable region of SEQ ID NO: 797; 44) the heavy chain variable region of SEQ ID NO: 770 and the light chain variable region of SEQ ID NO: 798; 45) the heavy chain variable region of SEQ ID NO: 771 and the light chain variable region of SEQ ID NO: 799;46) the heavy chain variable region of SEQ ID NO: 772 and the light chain variable region of SEQ ID NO: 800; 47) the heavy chain variable region of SEQ ID NO: 773 and the light chain variable region of SEQ ID NO: 801; 48) the heavy chain variable region of SEQ ID NO: 774 and the light chain variable region of SEQ ID NO: 802; 49) the heavy chain variable region of SEQ ID NO: 775 and the light chain variable region of SEQ ID NO: 803; 50) the heavy chain variable region of SEQ ID NO: 776 and the light chain variable region of SEQ ID NO: 804; 51) the heavy chain variable region of SEQ ID NO: 777 and the light chain variable region of SEQ ID NO: 805; 52) the heavy chain variable region of SEQ ID NO: 778 and the light chain variable region of SEQ ID NO: 806; 53) the heavy chain variable region of SEQ ID NO: 779 and the light chain variable region of SEQ ID NO: 807; 54) the heavy chain variable region of SEQ ID NO: 771 and the light chain variable region of SEQ ID NO: 808; 55) the heavy chain variable region of SEQ ID NO: 780 and the light chain variable region of SEQ ID NO: 808; 56) the heavy chain variable region of SEQ ID NO: 781 and the light chain variable region of SEQ ID NO: 809; 57) the heavy chain variable region of SEQ ID NO: 782 and the light chain variable region of SEQ ID NO: 810; or 58) the heavy chain variable region of SEQ ID NO: 783 and the light chain variable region of SEQ ID NO: 811.

[0317] As applied to any antibody conjugate, in some embodiments, the anti-Gal3 antibody or its binding fragment comprises a heavy chain (HC) sequence of any one of SEQ ID NOs: 188-216. Figure 26 Exemplary HC sequences are depicted in .

[0318] As applied to any antibody conjugate, in some embodiments, the anti-Gal3 antibody or its binding fragment comprises a light chain (LC) sequence of any one of SEQ ID NOs: 217-243. Figure 27 Exemplary LC sequences are depicted in .

[0319] As applied to any antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof is selected from TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, F846C.1B2, F846C.1F5, F846C.1H12, and F846C.1 H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12 , F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 847.14H4, 846T.1H2, 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, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847. The group consisting of at least one of 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, or a binding fragment thereof.As applied to any antibody conjugate, in some embodiments, the anti-Gal3 antibody or its binding fragment is selected from TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, F 846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F 846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B 10. F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846.2D4, 846.2F11, 846T.10B1, 846T.2E 3. 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, The group consisting of 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 or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or its binding fragment is selected from TB001, TB006, 19B5.2E6, 14H10.2C9, 15F10.2D6, 20H5.A3, 23H9.2E4, 2D10.2B2, 7D8.2D8, F846C.1B2, F846C.1F5, F846C.1H12, F846C.2H3, F846 TC.14E4, F846TC.16B5, F846TC.7F10, F849C.8D10, 846.4D5, 846T.4E11, 847.11D6, 847.20H7, 847.21B11, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F2, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody selected from 846.4D5, 15F10.2D6, F846C.1B2, and F846C.1H12. In some embodiments,. Figure 30The heavy and light chain CDRs associated with each of the aforementioned antibodies are depicted in . In some embodiments, Figure 31 The V associated with each of the aforementioned antibodies is depicted in H and V L In some embodiments, Figure 32 The HC and LC associated with each of the aforementioned antibodies are depicted in .

[0320] Also disclosed herein are multispecific antibodies comprising a first binding domain that binds to Gal3 and a second binding domain that binds to a therapeutic target molecule located in the brain of a subject. In some embodiments, the second binding domain, when not conjugated to an anti-Gal3 antibody or its binding fragment, cannot independently cross the blood-brain barrier or has low permeability across the blood-brain barrier. In some embodiments, the permeability of the second binding domain across the blood-brain barrier is less than 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1% of the permeability of the multispecific antibody across the blood-brain barrier. In some embodiments, the first binding domain that binds to Gal3 belongs to bin 3, 8, 17 or 24. In some embodiments, the first binding domain that binds to Gal3 disrupts the interaction between Gal3 and an antibody that belongs to bin 3, 8, 17 or 24. In some embodiments, the first binding domain that binds to Gal3 competes for binding to Gal3 with an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the first binding domain that binds to Gal3 is the binding domain of an anti-Gal3 antibody or binding fragment thereof of any one of the antibody conjugates of claims 109 to 133. In some embodiments, the first binding domain is the binding domain of any one of the anti-Gal3 antibodies or binding fragments thereof disclosed herein or the binding domain of any one of the antibody conjugates disclosed herein.

[0321] Also disclosed herein are pharmaceutical compositions comprising any one of the antibody conjugates or multispecific antibodies disclosed herein and at least one pharmaceutically acceptable diluent, excipient, or carrier.

[0322] Also disclosed herein are methods of delivering a cargo to the central nervous system of a subject in need thereof, comprising administering to the subject an antibody conjugate comprising an anti-Gal3 antibody or a binding fragment thereof and a cargo conjugated to the anti-Gal3 antibody or a binding fragment thereof, wherein the antibody conjugate is capable of crossing the blood-brain barrier.

[0323] Also disclosed herein are methods of increasing the permeability of a cargo across the blood-brain barrier of a subject in need thereof, comprising conjugating an anti-Gal3 antibody or a binding fragment thereof to the cargo to form an antibody conjugate. In some embodiments, the method further comprises administering the antibody conjugate to the subject.

[0324] As applied to any method comprising conjugating an anti-Gal3 antibody or binding fragment thereof to a cargo, in some embodiments, the subject is a mammal, such as a mouse, rat, other rodent, cat, dog, rabbit, cow, horse, sheep, pig, goat, or human. In some embodiments, the cargo does not normally cross the blood-brain barrier. In some embodiments, conjugating the cargo to the anti-Gal3 antibody or binding fragment thereof increases the permeability of the cargo across the blood-brain barrier by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, or 500%, or any increase within a range defined by any two of the above percentages, compared to the unconjugated cargo. In some embodiments, the penetrance of the cargo across the blood-brain barrier is less than 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1% of the penetrance of the antibody conjugate across the blood-brain barrier. In some embodiments, the cargo or the anti-Gal3 antibody or binding fragment thereof, or both, is used to treat a neurological disorder. In some embodiments, the neurological disorder comprises inflammation, encephalitis, Alzheimer's disease, Parkinson's disease, Huntington's disease, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, olfactory dysfunction, aphasia, Bell's palsy, transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease, fatal familial insomnia, epilepsy, spasticity, neurodevelopmental, Tourette syndrome, neuroinfectious disease, meningitis, encephalitis, mad cow disease, West Nile virus encephalitis, neuro-AIDS, fragile X syndrome, Guillain-Barré syndrome, brain metastasis or brain cancer (primary or secondary brain tumor) or any combination thereof. In some embodiments, the payload is a cytotoxic payload, a microtubule disrupting agent, a DNA modifying agent, an Akt inhibitor, a polymerase inhibitor, a detectable moiety, an immunomodulator, an immunomodulator, an immunotoxin, a nucleic acid polymer, an aptamer, a peptide, a protein, an enzyme or any combination thereof. In some embodiments, the payload is a second antibody. In some embodiments, the second antibody is incapable of independently crossing the blood-brain barrier or has low permeability across the blood-brain barrier when not conjugated to an anti-Gal3 antibody or binding fragment thereof. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the antibody conjugate is administered enterally, orally, intranasally, parenterally, intracranialy, subcutaneously, intramuscularly, intradermally, or intravenously, or any combination thereof.

[0325] As applied to any method comprising an antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to one or more peptides of SEQ ID NOs: 3-26. 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 belongs to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody belonging to bin 3, 8, 17, or 24. In some embodiments, the anti-Gal3 antibody or binding fragment thereof competes with an antibody belonging to bin 3, 8, 17, or 24 for binding to Gal3.

[0326] As applied to any method or use comprising an antibody conjugate, in some embodiments, an anti-Gal3 antibody or binding fragment thereof comprises any one or more sequences provided throughout the disclosure (e.g., V H -CDR1, V H -CDR2, V H -CDR3, V L -CDR1, V L -CDR2, V L -CDR3, heavy chain variable region, light chain variable region, heavy chain or light chain sequence). In some embodiments, the anti-Gal3 antibody or its binding fragment comprises Figure 18-32 any one or more sequences shown in , including any one or more CDRs, heavy chain variable regions, light chain variable regions, heavy chains, light chains, combinations of CDRs, combinations of variable regions, or combinations of heavy and light chains described herein. In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a polypeptide comprising a heavy chain variable region, a heavy chain variable region, a light chain variable region, ... Figures 37-40 The peptide sequence encoded by any one or more of the nucleic acid sequences shown in (including any nucleic acid sequence encoding a heavy chain variable region, a light chain variable region, a heavy chain or a light chain) has a peptide sequence that is at least 80%, 85%, 90%, 95%, 99% or 100% homologous.

[0327] As applied to any method comprising an antibody conjugate, in some embodiments, an anti-Gal3 antibody or binding fragment thereof comprises (1) a heavy chain variable region comprising V H -CDR1, V H -CDR2 and V H - CDR3, and (2) light chain variable region, which includes V L -CDR1, V L -CDR2 and VL -CDR3. In some embodiments, V H - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 27-44, 245-246, 588-615, V H - CDR2 comprises an amino acid sequence selected from SEQ ID NOs: 45-60, 247-248, 616-643, V H - CDR3 comprises an amino acid sequence selected from SEQ ID NO: 61-81, 249-250, 644-671, V L - CDR1 comprises an amino acid sequence selected from SEQ ID NOs: 82-101, 251-252, 672-699, V L - CDR2 comprises an amino acid sequence selected from SEQ ID NOs: 102-116, 253, 700-727 and V L - CDR3 comprises an amino acid sequence selected from SEQ ID NO: 117-135, 254-255, 728-755.

[0328] As applied to any method involving an antibody conjugate, in some embodiments, Figure 18 An exemplary V H -CDR1 sequence. In some embodiments, Figure 19 An exemplary V H -CDR2 sequence. In some embodiments, Figure 20 An exemplary V H -CDR3 sequence. In some embodiments, Figure 21 An exemplary V L -CDR1 sequence. In some embodiments, Figure 22 An exemplary V L -CDR2 sequence. In some embodiments, Figure 23 An exemplary V L -CDR3 sequence.

[0329] As applied to any method involving antibody conjugates, in some embodiments, the heavy chain variable region (V H ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 136-160, 256-257. In some embodiments, the heavy chain variable region is selected from the group consisting of SEQ ID NOs: 136-160, 256-257. In some embodiments, Figure 24 An exemplary V H .

[0330] As applied to any method involving antibody conjugates, in some embodiments, the light chain variable region (V L ) comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity to any of the sequences according to SEQ ID NOs: 161-187, 258-259. In some embodiments, the light chain variable region is selected from the group consisting of SEQ ID NOs: 161-187, 258-259. In some embodiments, Figure 25 An exemplary V L .

[0331] As applied to any method comprising an antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: 1) V within SEQ ID NO: 136 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 161 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 2) V within SEQ ID NO: 137 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 162 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 3) V within SEQ ID NO: 138 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 163 L-CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 4) V within SEQ ID NO: 139 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 164 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 5) V within SEQ ID NO: 140 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 165 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 6) V within SEQ ID NO: 141 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 166 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 7) V within SEQ ID NO: 142 H -CDR1, V H -CDR2, V H -V of CDR3H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:167 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 8) V within SEQ ID NO:143 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:168 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 9) V within SEQ ID NO:144 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:169 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 10) V within SEQ ID NO:145 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:170 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L-CDR3; 11) V within SEQ ID NO: 139 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 171 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 12) V within SEQ ID NO: 146 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 172 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 13) V within SEQ ID NO: 147 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 173 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 14) V within SEQ ID NO: 148 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 174 V L -CDR1, V L-CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 15) V within SEQ ID NO: 149 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 175 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 16) V within SEQ ID NO: 150 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 176 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 17) SEQ ID NO: 151 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 177 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 18) V within SEQ ID NO: 152 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, VH - CDR2, V H - CDR3 and V within SEQ ID NO:178 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 19) V within SEQ ID NO:153 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:179 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 20) V within SEQ ID NO:154 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:180 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 21) V within SEQ ID NO:155 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:181[[ID=​​​​​​​​​​​H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 182 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 23) SEQ ID NO: 157 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 183 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 24) SEQ ID NO: 155 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 184 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 25) V within SEQ ID NO: 158 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 185 L -CDR1, V L -CDR2, V L-V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 26) V within SEQ ID NO: 159 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 186 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 27) SEQ ID NO: 160 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 187 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 28) SEQ ID NO: 256 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 258 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 29) SEQ ID NO: 257 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, VH -CDR3 and V within SEQ ID NO: 259 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 30) SEQ ID NO: 756 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 784 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 31) SEQ ID NO: 757 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 785 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 32) SEQ ID NO: 758 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 786 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 33) SEQ ID NO: 759 V H-CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:787 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 34) V within SEQ IDNO:760 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:788 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 35) V within SEQ ID NO:761 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:789 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 36) V within SEQ ID NO:762 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:790 L -CDR1, V<� L -CDR2, V L -CDR3 of VL -CDR1, V L -CDR2, V L -CDR3; 37) SEQ ID NO: 763 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 791 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 38) SEQ ID NO: 764 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 792 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 39) SEQ ID NO: 765 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 793 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 40) SEQ ID NO: 766 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H-CDR3 and SEQ ID NO: 794 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 41) SEQ ID NO: 767 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 795 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 42) SEQ ID NO: 768 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 796 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 43) SEQ ID NO: 769 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 797 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 44) SEQ ID NO: 770 V H -CDR1, V H-CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:798 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 45) V within SEQ ID NO:771 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:799 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 46) V within SEQ ID NO:772 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:800 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 47) V within SEQ ID NO:773 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:801 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, VL - CDR2, V L - CDR3; 48) V within SEQ ID NO:774 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:802 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 49) V within SEQ ID NO:775 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:803 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V L - CDR2, V L - CDR3; 50) V within SEQ ID NO:776 H - CDR1, V H - CDR2, V H - V of CDR3 H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:804 L - CDR1, V L - CDR2, V L - V of CDR3 L - CDR1, V<000,4224>- CDR2, V L - CDR3; 51) V within SEQ ID NO:777 H - CDR1, V H - CDR2, V H H - CDR3 and V within SEQ ID NO:805​​​​​L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 52) SEQ ID NO: 778 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 806 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 53) SEQ ID NO: 779 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 807 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 54) SEQ ID NO: 780 V H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 808 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 55) SEQ ID NO: 781 V H -CDR1, V H -CDR2, V H-V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 809 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; 56) V within SEQ ID NO: 782 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO: 810 L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3; or 57) V within SEQ ID NO: 783 H -CDR1, V H -CDR2, V H -V of CDR3 H -CDR1, V H -CDR2, V H -CDR3 and SEQ ID NO: 811 V L -CDR1, V L -CDR2, V L -V of CDR3 L -CDR1, V L -CDR2, V L -CDR3. In some embodiments, Figure 28 Exemplary combinations of heavy chain variable region CDRs are depicted in . In some embodiments, Figure 29 Exemplary combinations of light chain variable region CDRs are depicted in .

[0332] As applied to any method comprising an antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises: 1) a heavy chain variable region of SEQ ID NO: 136 and a light chain variable region of SEQ ID NO: 161; 2) a heavy chain variable region of SEQ ID NO: 137 and a light chain variable region of SEQ ID NO: 162; 3) a heavy chain variable region of SEQ ID NO: 138 and a light chain variable region of SEQ ID NO: 163; 4) a heavy chain variable region of SEQ ID NO: 139 and a light chain variable region of SEQ ID NO: 164; 5) a heavy chain variable region of SEQ ID NO: 140 and a light chain variable region of SEQ ID NO: 165; 6) a heavy chain variable region of SEQ ID NO: 141 and a light chain variable region of SEQ ID NO: 166; 7) a heavy chain variable region of SEQ ID NO: 142 and a light chain variable region of SEQ ID NO: 167; 8) a heavy chain variable region of SEQ ID NO: 143 and a light chain variable region of SEQ ID NO: NO: 168; 9) the heavy chain variable region of SEQ ID NO: 144 and the light chain variable region of SEQ ID NO: 169; 10) the heavy chain variable region of SEQ ID NO: 145 and the light chain variable region of SEQ ID NO: 170; 11) the heavy chain variable region of SEQ ID NO: 139 and the light chain variable region of SEQ ID NO: 171; 12) the heavy chain variable region of SEQ ID NO: 146 and the light chain variable region of SEQ ID NO: 172; 13) the heavy chain variable region of SEQ ID NO: 147 and the light chain variable region of SEQ ID NO: 173; 14) the heavy chain variable region of SEQ ID NO: 148 and the light chain variable region of SEQ ID NO: 174; 15) the heavy chain variable region of SEQ ID NO: 149 and the light chain variable region of SEQ ID NO: 175; 16) the heavy chain variable region of SEQ ID NO: 150 and the light chain variable region of SEQ ID NO: 176; 17) 18) a heavy chain variable region of SEQ ID NO: 151 and a light chain variable region of SEQ ID NO: 177; 19) a heavy chain variable region of SEQ ID NO: 153 and a light chain variable region of SEQ ID NO: 179; 20) a heavy chain variable region of SEQ ID NO: 154 and a light chain variable region of SEQ ID NO: 180; 21) a heavy chain variable region of SEQ ID NO: 155 and a light chain variable region of SEQ ID NO: 181; 22) a heavy chain variable region of SEQ ID NO: 156 and a light chain variable region of SEQ ID NO: 182;23) the heavy chain variable region of SEQ ID NO: 157 and the light chain variable region of SEQ ID NO: 183; 24) the heavy chain variable region of SEQ ID NO: 155 and the light chain variable region of SEQ ID NO: 184; 25) the heavy chain variable region of SEQ ID NO: 158 and the light chain variable region of SEQ ID NO: 185; 26) the heavy chain variable region of SEQ ID NO: 159 and the light chain variable region of SEQ ID NO: 186; 27) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 187; 28) the heavy chain variable region of SEQ ID NO: 256 and the light chain variable region of SEQ ID NO: 258; 29) the heavy chain variable region of SEQ ID NO: 257 and the light chain variable region of SEQ ID NO: 259; 30) the heavy chain variable region of SEQ ID NO: 756 and the light chain variable region of SEQ ID NO: 784; 31) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 160; NO: 757 heavy chain variable region and SEQ ID NO: 785 light chain variable region; 32) SEQ ID NO: 758 heavy chain variable region and SEQ ID NO: 786 light chain variable region; 33) SEQ ID NO: 759 heavy chain variable region and SEQ ID NO: 787 light chain variable region; 34) SEQ ID NO: 760 heavy chain variable region and SEQ ID NO: 788 light chain variable region; 35) SEQ ID NO: 761 heavy chain variable region and SEQ ID NO: 789 light chain variable region; 36) SEQ ID NO: 762 heavy chain variable region and SEQ ID NO: 790 light chain variable region; 37) SEQ ID NO: 763 heavy chain variable region and SEQ ID NO: 791 light chain variable region; 38) SEQ ID NO: 764 heavy chain variable region and SEQ ID NO: 792 light chain variable region; 39) SEQ ID NO: 765 heavy chain variable region and SEQ ID NO: NO: 793; 40) the heavy chain variable region of SEQ ID NO: 766 and the light chain variable region of SEQ ID NO: 794; 41) the heavy chain variable region of SEQ ID NO: 767 and the light chain variable region of SEQ ID NO: 795; 42) the heavy chain variable region of SEQ ID NO: 768 and the light chain variable region of SEQ ID NO: 796; 43) the heavy chain variable region of SEQ ID NO: 769 and the light chain variable region of SEQ ID NO: 797; 44) the heavy chain variable region of SEQ ID NO: 770 and the light chain variable region of SEQ ID NO: 798; 45) the heavy chain variable region of SEQ ID NO: 771 and the light chain variable region of SEQ ID NO: 799;46) the heavy chain variable region of SEQ ID NO: 772 and the light chain variable region of SEQ ID NO: 800; 47) the heavy chain variable region of SEQ ID NO: 773 and the light chain variable region of SEQ ID NO: 801; 48) the heavy chain variable region of SEQ ID NO: 774 and the light chain variable region of SEQ ID NO: 802; 49) the heavy chain variable region of SEQ ID NO: 775 and the light chain variable region of SEQ ID NO: 803; 50) the heavy chain variable region of SEQ ID NO: 776 and the light chain variable region of SEQ ID NO: 804; 51) the heavy chain variable region of SEQ ID NO: 777 and the light chain variable region of SEQ ID NO: 805; 52) the heavy chain variable region of SEQ ID NO: 778 and the light chain variable region of SEQ ID NO: 806; 53) the heavy chain variable region of SEQ ID NO: 779 and the light chain variable region of SEQ ID NO: 807; 54) 55) the heavy chain variable region of SEQ ID NO: 780 and the light chain variable region of SEQ ID NO: 808; 56) the heavy chain variable region of SEQ ID NO: 781 and the light chain variable region of SEQ ID NO: 809; 57) the heavy chain variable region of SEQ ID NO: 782 and the light chain variable region of SEQ ID NO: 810; or 58) the heavy chain variable region of SEQ ID NO: 783 and the light chain variable region of SEQ ID NO: 811.

[0333] As applied to any method comprising an antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain (HC) sequence of any one of SEQ ID NOs: 188-216. In some embodiments, Figure 26 Exemplary HC sequences are depicted in .

[0334] As applied to any method comprising an antibody conjugate, in some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a light chain (LC) sequence of any one of SEQ ID NOs: 217-243. Figure 27 Exemplary LC sequences are depicted in .

[0335] As applied to any method comprising an antibody conjugate, 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, F846C.1B2, F846C.1F5, F846C.1H2, and F846. C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F 12. F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 847.14H4, 846T.1H2, mIMT001, 4A11.2 B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23 B10.2B12, 24D12.2H9, 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 or at least one binding fragment thereof.As applied to any method comprising an antibody conjugate, in some embodiments, an anti-Gal3 antibody or binding fragment thereof is selected from TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D 8. F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4 , F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C. 4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846.2D4, 846.2F11, 846T.10B1, 846T.2 E3, 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 or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or its binding fragment is selected from TB001, TB006, 19B5.2E6, 14H10.2C9, 15F10.2D6, 20H5.A3, 23H9.2E4, 2D10.2B2, 7D8.2D8, F846C.1B2, F846C.1F5, F846C.1H12, F846C.2H3, F846 TC.14E4, F846TC.16B5, F846TC.7F10, F849C.8D10, 846.4D5, 846T.4E11, 847.11D6, 847.20H7, 847.21B11, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F2, or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or binding fragment thereof disrupts the interaction between Gal3 and an antibody selected from 846.4D5, 15F10.2D6, F846C.1B2, and F846C.1H12.In some embodiments, the anti-Gal3 antibody or binding fragment thereof competes for binding to Gal3 with an antibody belonging to bin 3, 8, 17, or 24. In some embodiments,. Figure 30 The heavy and light chain CDRs associated with each of the aforementioned antibodies are depicted in . In some embodiments, Figure 31 The V associated with each of the aforementioned antibodies is depicted in H and V L In some embodiments, Figure 32 The HC and LC associated with each of the aforementioned antibodies are depicted in . Method of use – disruption of cell surface markers

[0336] Galectin-3 (Gal3) is known to play an important role in cell proliferation, adhesion, differentiation, angiogenesis and apoptosis. This activity is at least in part due to immunomodulatory properties and binding affinity to other immunomodulatory proteins, signaling proteins and other cell surface markers. As disclosed herein, Gal3 shows direct binding to TGF-β receptors, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3 IIIc or FGFR4 or any combination thereof. Therefore, Gal3 can contribute to pro-inflammatory or anti-inflammatory responses and inflammation-related disorders. Gal3 works through different N-terminal and C-terminal domains. The N-terminal domain (amino acids 1-111) contains the tandem repeat domain (TRD, amino acids 36-109) and is largely responsible for the oligomerization of Gal3. The C-terminal domain (amino acids 112-250) contains the carbohydrate recognition binding domain (CRD), which binds to β-galactosidase.

[0337] In some embodiments, methods are disclosed for blocking or disrupting the interaction between a TGF-β receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3IIIc or FGFR4, or any combination thereof, either in vitro or in vivo using any one or more anti-Gal3 antibodies or binding fragments thereof.

[0338] In some embodiments, the method is directed to disrupting the interaction between Gal3 and the TGF-b receptor. In some embodiments, the method comprises contacting the interaction between Gal and the TGF-b receptor with an antibody or binding fragment thereof (such as any anti-Gal3 antibody or binding fragment thereof disclosed herein) that selectively binds to Gal3 and disrupts the interaction between Gal3 and the TGF-b receptor. In some embodiments, Gal3 is expressed by cells. In some embodiments, Gal3 is secreted by cells. In some embodiments, the TGF-b receptor is expressed by cells.

[0339] In some embodiments, the method is directed to treating fibrosis in a subject in need thereof. In some embodiments, the method comprises administering to the subject an antibody or binding fragment thereof that selectively binds to Gal3 and disrupts the interaction between Gal3 and the TGF-b receptor (such as any anti-Gal3 antibody or binding fragment thereof disclosed herein), thereby treating the subject's fibrosis. In some embodiments, the fibrosis is hepatic fibrosis, renal fibrosis, cardiac fibrosis, arterial fibrosis, venous thrombosis, or pulmonary fibrosis.

[0340] In some embodiments, the method is directed to treating non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in a subject in need thereof. In some embodiments, the method comprises administering to the subject an antibody or binding fragment thereof that selectively binds to Gal3 and disrupts the interaction between Gal3 and the TGF-b receptor (such as any anti-Gal3 antibody or binding fragment thereof disclosed herein), thereby treating NAFLD or NASH in the subject.

[0341] In some embodiments, the method is directed to treating an immune-related disorder in a subject in need thereof. In some embodiments, the method comprises administering to the subject an antibody or its binding fragment (such as any anti-Gal3 antibody or its binding fragment disclosed herein) that selectively binds to Gal3 and destroys the interaction between Gal3 and TGF-b receptor, thereby treating the subject's immune-related disorder. In some embodiments, the immune-related disorder is sepsis, atopic dermatitis, or psoriasis. In some embodiments, the immune-related disorder is cancer. In some embodiments, the antibody or its binding fragment is administered as a supplement to PD1 / PDL1 blocking therapy and / or CTLA4 blocking therapy. In some embodiments, PD1 / PDL1 blockade therapy comprises pembrolizumab, nivolumab, cemiprilizumab, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, AMP-224, AMP-514, atezolizumab, avelumab, durvalumab, KN035, CK-301, AUNP12, CA-170 and / or BMS-986189. In some embodiments, CTLA4 blockade therapy comprises ipilimumab and / or tremelimumab.

[0342] As applied to any of the methods disclosed herein involving disruption of the interaction between Gal3 and a TGF-b receptor, the TGF-b receptor is TGF-b receptor 1, TGF-b receptor 2, or TGF-b receptor 3.

[0343] Also disclosed herein are methods for disrupting the interaction between Gal3 and tumor cell surface markers. In some embodiments, the method comprises contacting the tumor cell surface marker with an anti-Gal3 antibody or binding fragment thereof specific for the N-terminal domain of Gal3, the N-terminus of Gal3, or the TRD of Gal3. In some embodiments, the tumor cell surface marker is selected from the group consisting of VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR (cMet), TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3 IIIc, and FGFR4.

[0344] Also disclosed herein, in some embodiments, are methods for disrupting the interaction between Gal3 and TGF-b receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3 IIIc or FGFR4, or any combination thereof. In some embodiments, the method comprises contacting the interaction site between Gal3 and TGF-b receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3IIIc, or FGFR4, or any combination thereof, with an antibody or binding fragment thereof that selectively binds to Gal3 and disrupts the interaction between Gal3 and TGF-b receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR, TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3IIIc, or FGFR4, or any combination thereof.

[0345] Also disclosed herein are methods for treating cancer in subjects in need thereof. In some embodiments, the method comprises administering to the subject an anti-Gal3 antibody or its binding fragment specific for the N-terminal domain of Gal3, the N-terminus of Gal3, or the TRD of Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment disrupts the interaction between Gal3 and tumor cell surface markers, and the tumor cell surface markers are selected from the group consisting of VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR (cMet), TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3 IIIc, and FGFR4. In some embodiments, the cancer is brain cancer, breast cancer, colorectal cancer, kidney cancer, liver cancer, lung cancer, pancreatic cancer, bladder cancer, gastric cancer, or a malignant blood tumor. In some embodiments, the method further comprises administering standard of care therapy, and the anti-Gal3 antibody or its binding fragment is used as a supplement to standard of care therapy. In some embodiments, standard of care therapy comprises surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, PD1 / PDL1 blockade therapy, CTLA4 blockade therapy, temozolomide, or any combination thereof.

[0346] In some embodiments, the interaction between Gal3 and a cell surface marker or tumor surface marker can 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%.

[0347] In some embodiments, the antibody or binding fragment thereof binds to Gal3 with a dissociation constant (KD) 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.

[0348] In some embodiments, the interaction between Gal3 and TGF-β receptor, VEGFR1, VEGFR2, VEGFR3, EGFR, PDGFRa, PDGFRb, ErbB2, HGFR (cMet), TNF sRI, CTLA4, CD47, PD-L1, FGFR1α-IIIb, FGFR1α-IIIc, FGFR2α-IIIc, FGFR3 IIIc or FGFR4 can 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%. [03...

Claims

1. An anti-Gal3 antibody or a binding fragment thereof, comprising: (1) a heavy chain variable region, comprising V H -CDR1, V H -CDR2 and V H -CDR3, and (2) a light chain variable region, which includes V L -CDR1, V L -CDR2 and V L -CDR3; wherein V H - CDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 36-44, 588-615, V H - CDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 54-60, 616-643, V H - CDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 70-81, 644-671, V L - CDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 92-101, 672-699, V L - CDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 111-116, 700-727, and V L - CDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 127-135, 728-755.

2. The anti-Gal3 antibody or binding fragment thereof according to claim FICIC-2, wherein the heavy chain variable region comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity with any sequence according to SEQ ID NO: 147-160, 756-783.

3. The anti-Gal3 antibody or binding fragment thereof according to claim 1 or 2, wherein the heavy chain variable region is selected from the group consisting of SEQ ID NO: 147-160, 756-783.

4. The anti-Gal3 antibody or binding fragment thereof according to any one of claims 1 to 3, wherein the light chain variable region comprises an amino acid sequence having at least 75%, 80%, 85%, 90%, 95% or 100% sequence identity with any sequence according to SEQ ID NO: 173-187, 784-811.

5. The anti-Gal3 antibody or binding fragment thereof according to any one of claims 1 to 4, wherein the light chain variable region is selected from the group consisting of SEQ ID NOs: 173-187, 784-811.

6. The anti-Gal3 antibody or binding fragment thereof according to any one of claims 1 to 5, comprising: 1) V within SEQ ID NO:147 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:173 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 2) V within SEQ ID NO:148 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:174 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 3) V within SEQ ID NO:149 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:175 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 4) V within SEQ ID NO:150 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:176 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 5) V within SEQ ID NO:151 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:177 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 6) V within SEQ ID NO:152 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:178 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 7) V within SEQ ID NO:153 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:179 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3 8) V within SEQ ID NO:154 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:180 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 9) V within SEQ ID NO:155 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:181 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 10) V within SEQ ID NO:156 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:182 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 11) V within SEQ ID NO:157 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:183 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 12) V within SEQ ID NO:155 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:184 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 13) V within SEQ ID NO:158 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:185 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 14) V within SEQ ID NO:159 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:186 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 15) V within SEQ ID NO:160 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:187 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 16) V within SEQ ID NO:756 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:784 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 17) V within SEQ ID NO:757 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:785 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 18) V within SEQ ID NO:758 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:786 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 19) V within SEQ ID NO:759 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:787 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; V within SEQ ID NO:760 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:788 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 21) V within SEQ ID NO:761 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:789 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 22) V within SEQ ID NO:762 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:790 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; V within SEQ ID NO:763 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:791 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; V within SEQ ID NO:764 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:792 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 25) V within SEQ ID NO:765 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:793 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 26) V within SEQ ID NO:766 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:794 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 27) V within SEQ ID NO:767 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:795 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 28) V within SEQ ID NO:768 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:796 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 29) V within SEQ ID NO:769 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:797 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; V within SEQ ID NO:770 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:798 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; V within SEQ ID NO:771 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:799 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; V within SEQ ID NO:772 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:800 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; V within SEQ ID NO:773 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:801 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 34) V within SEQ ID NO:774 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:802 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; V within SEQ ID NO:775 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:803 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 36) V within SEQ ID NO:776 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:804 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; V within SEQ ID NO:777 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:805 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 38) V within SEQ ID NO:778 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:806 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 39) V within SEQ ID NO:779 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:807 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; V within SEQ ID NO:780 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:808 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3; 41) V within SEQ ID NO:781 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:809 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; 42) V within SEQ ID NO:782 H - CDR1, V H - CDR2, V H - CDR3 of V H - CDR1, V H - CDR2, V H - CDR3 and V within SEQ ID NO:810 L - CDR1, V L - CDR2, V L - CDR3 of V L - CDR1, V L - CDR2, V L - CDR3; or V within SEQ ID NO:783 H -CDR1, V H -CDR2, V H -CDR3 of V H -CDR1, V H -CDR2, V H -CDR3 and V within SEQ ID NO:811 L -CDR1, V L -CDR2, V L -CDR3 of V L -CDR1, V L -CDR2, V L -CDR3.

7. The anti-Gal3 antibody or binding fragment thereof according to any one of claims 1 to 6, comprising: 1) the heavy chain variable region of SEQ ID NO: 147 and the light chain variable region of SEQ ID NO: 173; 2) a heavy chain variable region of SEQ ID NO: 148 and a light chain variable region of SEQ ID NO: 174; 3) the heavy chain variable region of SEQ ID NO: 149 and the light chain variable region of SEQ ID NO: 175; 4) a heavy chain variable region of SEQ ID NO: 150 and a light chain variable region of SEQ ID NO: 176; 5) the heavy chain variable region of SEQ ID NO: 151 and the light chain variable region of SEQ ID NO: 177; 6) the heavy chain variable region of SEQ ID NO: 152 and the light chain variable region of SEQ ID NO: 178; 7) the heavy chain variable region of SEQ ID NO: 153 and the light chain variable region of SEQ ID NO: 179; 8) the heavy chain variable region of SEQ ID NO: 154 and the light chain variable region of SEQ ID NO: 180; 9) the heavy chain variable region of SEQ ID NO: 155 and the light chain variable region of SEQ ID NO: 181; 10) a heavy chain variable region of SEQ ID NO: 156 and a light chain variable region of SEQ ID NO: 182; 11) the heavy chain variable region of SEQ ID NO: 157 and the light chain variable region of SEQ ID NO: 183; 12) a heavy chain variable region of SEQ ID NO: 155 and a light chain variable region of SEQ ID NO: 184; 13) a heavy chain variable region of SEQ ID NO: 158 and a light chain variable region of SEQ ID NO: 185; 14) the heavy chain variable region of SEQ ID NO: 159 and the light chain variable region of SEQ ID NO: 186; 15) the heavy chain variable region of SEQ ID NO: 160 and the light chain variable region of SEQ ID NO: 187; 16) the heavy chain variable region of SEQ ID NO: 756 and the light chain variable region of SEQ ID NO: 784; 17) the heavy chain variable region of SEQ ID NO: 757 and the light chain variable region of SEQ ID NO: 785; 18) the heavy chain variable region of SEQ ID NO: 758 and the light chain variable region of SEQ ID NO: 786; 19) the heavy chain variable region of SEQ ID NO: 759 and the light chain variable region of SEQ ID NO: 787; 20) the heavy chain variable region of SEQ ID NO: 760 and the light chain variable region of SEQ ID NO: 788; 21) the heavy chain variable region of SEQ ID NO: 761 and the light chain variable region of SEQ ID NO: 789; 22) the heavy chain variable region of SEQ ID NO: 762 and the light chain variable region of SEQ ID NO: 790; 23) the heavy chain variable region of SEQ ID NO: 763 and the light chain variable region of SEQ ID NO: 791; 24) the heavy chain variable region of SEQ ID NO: 764 and the light chain variable region of SEQ ID NO: 792; 25) the heavy chain variable region of SEQ ID NO: 765 and the light chain variable region of SEQ ID NO: 793; 26) the heavy chain variable region of SEQ ID NO: 766 and the light chain variable region of SEQ ID NO: 794; 27) the heavy chain variable region of SEQ ID NO: 767 and the light chain variable region of SEQ ID NO: 795; 28) the heavy chain variable region of SEQ ID NO: 768 and the light chain variable region of SEQ ID NO: 796; 29) the heavy chain variable region of SEQ ID NO: 769 and the light chain variable region of SEQ ID NO: 797; 30) the heavy chain variable region of SEQ ID NO: 770 and the light chain variable region of SEQ ID NO: 798; 31) the heavy chain variable region of SEQ ID NO: 771 and the light chain variable region of SEQ ID NO: 799; 32) the heavy chain variable region of SEQ ID NO: 772 and the light chain variable region of SEQ ID NO: 800; 33) the heavy chain variable region of SEQ ID NO: 773 and the light chain variable region of SEQ ID NO: 801; 34) the heavy chain variable region of SEQ ID NO: 774 and the light chain variable region of SEQ ID NO: 802; 35) the heavy chain variable region of SEQ ID NO: 775 and the light chain variable region of SEQ ID NO: 803; 36) the heavy chain variable region of SEQ ID NO: 776 and the light chain variable region of SEQ ID NO: 804; 37) the heavy chain variable region of SEQ ID NO: 777 and the light chain variable region of SEQ ID NO: 805; 38) the heavy chain variable region of SEQ ID NO: 778 and the light chain variable region of SEQ ID NO: 806; 39) the heavy chain variable region of SEQ ID NO: 779 and the light chain variable region of SEQ ID NO: 807; 40) the heavy chain variable region of SEQ ID NO: 780 and the light chain variable region of SEQ ID NO: 808; 41) the heavy chain variable region of SEQ ID NO: 781 and the light chain variable region of SEQ ID NO: 809; 42) the heavy chain variable region of SEQ ID NO: 782 and the light chain variable region of SEQ ID NO: 810; or 43) The heavy chain variable region of SEQ ID NO: 783 and the light chain variable region of SEQ ID NO:

811.

8. The anti-Gal3 antibody or binding fragment thereof according to any one of claims 1 to 7, wherein the anti-Gal3 antibody or binding fragment thereof is selected from F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846C.2B11, 846C.2D5, 846C.2H3. 46.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1 , 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21 B11, 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 or a combination fragment thereof.

9. The anti-Gal3 antibody or its binding fragment according to any one of claims 1-8, wherein the anti-Gal3 antibody or its binding fragment is selected from the group consisting of F846C.1B2, F846C.1F5, F846C.1H12, F846C.2H3, F846TC.14E4, F846TC.16B5, F846TC.7F10, F849C.8D10, 846.4D5 or its binding fragment.

10. The anti-Gal3 antibody or binding fragment thereof according to any one of claims 1 to 10, wherein the anti-Gal3 antibody or binding fragment thereof binds to one or more peptides of SEQ ID NOs: 3-26.

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