Methods and compositions for treating neurodevelopmental disorders

Abstract

Provided herein are therapies involving the use of antibodies that bind to Gal-3. Such therapies can include, but are not limited to, treating neurodevelopmental disorders like autism spectrum disorder (ASD) and / or symptoms thereof and attention deficit hyperactivity disorder (ADHD) and / or symptoms thereof. In some embodiments, subjects identified as suffering from ASD or ADHD and / or symptoms thereof may be administered an anti-Gal3 antibody or a binding fragment thereof, wherein administration of the anti-Gal3 antibody treats and / or reduces the development of ASD or ADHD and / or associated symptoms thereof in the subject. In some embodiments the anti-Gal3 antibody comprises TB006, or a fragment thereof.

Description

IMMUT.048WO PATENT METHODS AND COMPOSITIONS FOR TREATING NEURODEVELOPMENTAL DISORDERS INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

[0001] This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 662737, filed June 21, 2024, which is hereby expressly incorporated by reference in its entirety, including any appendices filed therewith. REFERENCE TO SEQUENCE LISTING

[0002] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled IMMUT048WOSEQLIST.XML, which was created and last modified on June 18, 2025, which is 2,996,991 bytes in size. The information in the electronic Sequence Listing is hereby incorporated by reference in its entirety. FIELD

[0003] Aspects of the present disclosure relate generally to therapies involving the use of antibodies that bind to Gal-3. BACKGROUND

[0004] Galectin-3 (Gal3, GAL3, LGALS3) is a lectin, or a carbohydrate-binding protein, with specificity towards beta-galactosides. In human cells, Gal3 is expressed and can be found in the nucleus, cytoplasm, cell surface, and in the extracellular space. Gal3 recognizes and interacts with beta-galactose conjugates on various proteins. SUMMARY

[0005] Some embodiments provided herein are described by way of the following provided embodiments and also provided as possible combinations or overlapping embodiments:

[0006] Some embodiments herein relate to methods of treating or reducing the development of an autism spectrum disorder (ASD) or associated symptoms thereof in a subjectin need thereof. In some embodiments, the methods comprise: identifying a subject as having or being at risk of having ASD or associated symptoms thereof, and administering an anti-Gal3 antibody or a binding fragment thereof to the subject. In some embodiments, administration of the anti-Gal3 antibody treats and / or reduces the development of ASD or associated symptoms thereof in the subject. In some embodiments, the associated symptoms comprise at least one of impaired social communication, impaired cognitive skills, impaired social cognitive skills, impaired motor function, impaired attention, or emotional abnormalities. In some embodiments, the anti-Gal3 antibody is TB006 or comprises a fragment thereof.

[0007] Some embodiments herein relate to methods of reducing and / or inhibiting the activity of Galectin-3 (Gal3) in a subject with an autism spectrum disorder (ASD) or associated symptoms thereof. In some embodiments, the methods comprise: identifying a subject as having or being at risk of having ASD or associated symptoms thereof, and administering an anti-Gal3 antibody or a binding fragment thereof to the subject. In some embodiments, administration of the anti-Gal3 antibody reduces and / or inhibits the activity of Gal3 in the subject as compared to the activity of Gal3 in the subject prior to administration of the anti-Gal3 antibody. In some embodiments, the associated symptoms comprise at least one of impaired social communication, impaired cognitive skills, impaired social cognitive skills, impaired motor function, impaired attention, or emotional abnormalities. In some embodiments, the anti-Gal3 antibody is TB006 or a comprises a fragment thereof.

[0008] Some embodiments herein relate to methods of treating or reducing the development of an attention deficit hyperactivity disorder (ADHD) or associated symptoms thereof in a subject in need thereof. In some embodiments, the methods comprise: identifying a subject as having or being at risk of having ADHD or associated symptoms thereof, and administering an anti-Gal3 antibody or a binding fragment thereof to the subject. In some embodiments, administration of the anti-Gal3 antibody treats and / or reduces the development of ADHD or associated symptoms thereof in the subject. In some embodiments, the associated symptoms comprise impaired cognitive functions, impaired psychosocial functions or impaired behavioral functions. In some embodiments, the anti-Gal3 antibody is TB006 or a comprises a fragment thereof.

[0009] Some embodiments herein relate to methods of reducing and / or inhibiting the activity of Galectin-3 (Gal3) in a subject with an attention deficit hyperactivity disorder (ADHD)or associated symptoms thereof. In some embodiments, the methods comprise: identifying a subject as having or being at risk of having ADHD or associated symptoms thereof, and administering an anti-Gal3 antibody or a binding fragment thereof to the subject. In some embodiments, administration of the anti-Gal3 antibody reduces and / or inhibits the activity of Gal3 in the subject as compared to the level of Gal3 in the subject prior to administration of the anti- Gal3 antibody. In some embodiments, the associated symptoms comprise impaired cognitive functions, impaired psychosocial functions or impaired behavioral functions. In some embodiments, the anti-Gal3 antibody is TB006 or a comprises a fragment thereof.

[0010] In some embodiments, administering the anti-Gal3 antibody or a binding fragment thereof to the subject comprises administration of one or more-unit doses of the anti- Gal3 antibody or a binding fragment thereof, optionally 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 unit doses. In some embodiments, the one or more unit doses comprise 10, 20, 20, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2500, 3000, 3500, 4000, 4500 or 5000 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose, or any amount per unit dose within a range defined by any two of the aforementioned amounts per unit dose. In some embodiments, the one or more unit doses comprise about 4000 mg of the anti-Gal3 antibody or binding fragment thereof. In some embodiments, the one or more unit doses comprise 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, or 150 mg / kg weight of the subject, or any amount per unit dose within a range defined by any two of the aforementioned amounts per unit dose. In some embodiments, the one or more unit doses comprise about 60mg / kg of the antibody by weight of the subject. In some embodiments, the one or more-unit doses are administered every 1, 2, 3, 4, 5, 6, or 7 days, or 1, 2, 3, or 4 weeks, or any interval within a range defined by any two of the aforementioned intervals. In some embodiments, the one or more unit doses are administered every 1, 2, 3 or 4 weeks. In some embodiments the one or more unit doses are administered every 4 weeks. In some embodiments the one or more unit doses are administered intravenously.

[0011] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises TB006 or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH- CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 31; the VH-CDR2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 72; the VH-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 113; the VH-CDR1 comprises an amino acid sequence having at least 90%identity to SEQ ID NO: 171; the VH-CDR1 comprises an amino acid sequence having at least 90%identity to SEQ ID NO: 222; and the VH-CDR1 comprises an amino acid sequence having at least 90%, to SEQ ID NO: 249.

[0012] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3, and a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3; wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 1940 or 1764, the VH-CDR2 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 77 or 1781, the VH-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 118 or 1798, the VL-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 178 or 1815, the VL-CDR2 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 229 or 1831, and the VL-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 256 or 1849.

[0013] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 1 VL-CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs:170-296, or 1814-1864. In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VL-CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs:170-296, or 1814-1864.

[0014] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 1 VH-CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-169, 801, 802, 951-954, 1763-1813, or 1940. In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VH-CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-169, 801, 802, 951-954, 1763-1813, or 1940. In some embodiments, the anti-Gal3 antibody comprises at least 1 CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-296, 801, 802, 951-954, 1763- 1813, or 1940. In some embodiments, the anti-Gal3 antibody comprises at least 6 CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-296, 801, 802, 951- 954, 1763-1813, or 1940.

[0015] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-70, 1763-1779, or 1940; the VH-CDR2 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 71- 111, 801, 951, 952, or 1780-1796; the VH-CDR3 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NO: 112-169, 802, 953, 954, or 1797-1813; the VL-CDR1 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220, 1814-1830; the VL-CDR2 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 221-247, or 1831-1847; and the VL-CDR3 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 248-296, or 1848-1864.

[0016] In some embodiments, the anti-Gal3 antibody comprises a combination of the VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 as illustrated in FIG.7. In some embodiments, the antibody comprises at least 1 CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220, 221-247, 248-296, 27-70, 71-111, 801, 951-952, 112-169, 802, 953-954, 1763-1864, or 1940. In some embodiments, the antibody comprises at least 6 CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220, 221-247, 248-296, 27-70, 71-111, 801, 951-952,112-169, 802 , 953-954 , 1763-1864 or 1940.

[0017] In some embodiments, the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain variable region comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 940, 955-968, 1067-1109, 1415-1439, or 1882-1898.

[0018] In some embodiments, the anti-Gal3 antibody comprises a light chain, wherein the light chain variable region comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, 1440-1464, 1899- 1914, or 1921. In some embodiments, the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, 1465-1489, or 1679-1694. In some embodiments, the anti-Gal3 antibody comprises a light chain, wherein the light chain comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, 1490-1514, or 1713-1728. In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL- CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VH-CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 31, 72, 113, 37, 77, 118, 1764, 1781, or 1798.

[0019] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VH-CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 171, 222, 249, 178, 229, 256, 1815, 1831, or 1849. In some embodiments, the anti-Gal3 antibody comprises a heavy chain variable region, wherein the heavy chain variable region comprises a sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NO: 298, 1067, 814, 1928, 1920, or 1930. In some embodiments, the anti-Gal3 antibody comprises a light chain variable region, wherein the light chain variable region comprises a sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NO: 375, 1110, 829, 1931, 1932, or 1933.

[0020] In some embodiments, the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to SEQ ID NO: 449, 1153, 844,1934, 1695, or 1935. In some embodiments, the anti-Gal3 antibody comprises a light chain, wherein the light chain comprises a sequence having at least 90% identity to SEQ ID NO: 496, 1196, 859, 1936, 1746, or 1937.

[0021] In some embodiments, the anti-Gal3 antibody comprises a heavy chain variable region, wherein the heavy chain variable region comprises a sequence having at least 90% identity to SEQ ID NO: 309. In some embodiments, the anti-Gal3 antibody comprises a light chain variable region, wherein the light chain variable region comprises a sequence having at least 90% identity to SEQ ID NO: 387. In some embodiments, the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the SEQ ID NO: 462. In some embodiments, the anti-Gal3 antibody comprises a light chain, wherein the light chain comprises a sequence having at least 90% identity to SEQ ID NO: 508.

[0022] In some embodiments, the anti-Gal3 antibody 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, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, 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, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4- HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10- hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, 2D10-VH0-VL0, 2D10-hVH4- HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10- hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4,21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or binding fragment thereof.

[0023] In some embodiments, the anti-Gal3 antibody is administered at 5mg / kg to 150mg / kg weight of the subject. In some embodiments, the anti-Gal3 antibody is administered at 60mg / kg of the antibody by weight of the subject. In some embodiments, about 4000 mg of the anti-Gal3 antibody or binding fragment thereof is administered. In some embodiments, the anti- Gal3 antibody is administered at least once per week. In some embodiments the anti-Gal3 antibody or binding fragment thereof is administered every 2, 3 or 4 weeks. In some embodiments the anti- Gal3 antibody or binding fragment thereof is administered every 4 weeks. In some embodiments the anti-Gal3 antibody or binding fragment thereof is administered intravenously. In some embodiments, the subject is a human. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In addition to the features described above, additional features and variations will be readily apparent from the following descriptions of the drawings and exemplary embodiments. It is to be understood that these drawings depict typical embodiments and are not intended to be limiting in scope.

[0025] FIG. 1 depicts protein sequences of Gal3 and exemplary proteins that exhibit pathogenic aggregation.

[0026] FIG. 2 depicts peptide sequences of Gal3 used to generate and analyze antibodies.

[0027] FIG.3A depicts exemplary variable heavy chain complementarity-determining region (CDR) 1 for anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the variable heavy chain CDR1 provided herein.

[0028] FIG. 3B depicts exemplary variable heavy chain CDR2 for anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the variable heavy chain CDR2 provided herein.

[0029] FIG. 3C depicts exemplary variable heavy chain CDR3 for anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the variable heavy chain CDR3 provided herein.

[0030] FIG.4A depicts exemplary variable light chain CDR1 for anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the variable light chain CDR1 provided herein.

[0031] FIG.4B depicts exemplary variable light chain CDR2 for anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the variable light chain CDR2 provided herein.

[0032] FIG.4C depicts exemplary variable light chain CDR3 for anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the variable light chain CDR3 provided herein.

[0033] FIG.5 depicts exemplary heavy chain variable region (VH) sequences for anti- Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the VH sequences provided herein.

[0034] FIG. 6 depicts exemplary light chain variable region (VL) sequences for anti- Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the VL sequences provided herein.

[0035] FIG.7 depicts exemplary combinations of heavy and light chain CDRs (CDR1, CDR2, and CDR3) of exemplary anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy and light chain CDR combinations provided herein.

[0036] FIG. 8 depicts exemplary combinations of heavy and light chain variable regions of exemplary anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy and light chain variable region combinations provided herein.

[0037] FIG. 9 depicts exemplary heavy chain (HC) sequences and light chain (LC) sequences, and possible pairings for exemplary anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the HC or LC, or pairs of HC and LC sequences provided herein.

[0038] FIG.10 depicts antibody names used throughout the present disclosure refer to the same antibody (with exemplary peptide and nucleic acid sequences provided elsewhere in the disclosure and appropriately attributed to at least one of the depicted names) and may be used interchangeably. The names shown in a column correspond to the same antibody.

[0039] FIG. 11 depicts an alignment of hinge and constant heavy chain domain 2 (CH2) domain amino acid sequences of wild-type human immunoglobulin G1 (IgG1), IgG2 and IgG4 as well as their sigma variants. The alignment above uses EU numbering. Residues identical to wild-type IgG1 are indicated as dots; gaps are indicated with hyphens. Sequence is given explicitly if it differs from wild-type IgG1 or from the parental subtype for σ variants. Open boxes beneath the alignment correspond to International Immunogenetics Information System (IMGT) strand definitions. Boxes beneath the alignment correspond to the strand and helix secondary structure assignment for wild-type IgG1. Residues 267-273 form the BC loop and 322-332 form the FG loop. Also provided are exemplary constant regions for human IgG4 heavy (S228P mutant) and light (kappa) chains (SEQ ID NOs: 931-932) and murine IgG2A (LALAPG and LALA mutants) (SEQ ID NOs: 933-934). In some embodiments, any one or more of the VH / VL and / or CDRs provided in the other figures or otherwise disclosed herein can be paired with any one or more of the exemplary constant regions provided herein.

[0040] FIG. 12 depicts nucleic acid sequences that encode for exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy chain variable regions encoded by the nucleic acids provided herein.

[0041] FIG. 13 depicts nucleic acid sequences that encode for exemplary light chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the light chain variable regions encoded by the nucleic acids provided herein.

[0042] FIG.14 depicts nucleic acid sequences that encode for exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the heavy chains encoded by the nucleic acids provided herein.

[0043] FIG. 15 depicts nucleic acid sequences that encode for exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein can include one or more of the light chains encoded by the nucleic acids provided herein.

[0044] FIG. 16A-B depicts an exemplary alignment for the heavy chain CDRs (FIG. 16A) and light chain CDRs (FIG. 16B) for the exemplary anti-Gal3 antibodies disclosed herein.

[0045] FIG.17 is an illustrative representation of expression of Gal-3 in microglia using immunofluorescence staining of mouse brain sections in Alzheimer’s disease (AD) and stroke models. Iba-1 was used as a microglia marker. FIG. 17 shows that Gal3 was colocalized with microglia as the Gal3 expression overlaps with the expression of microglial marker, Iba-1. DAPI was used to stain the nucleus.

[0046] FIGS. 18A-18D are illustrations depicting an embodiment of inhibition of microglial activation by anti-Gal3 antibodies. FIG. 18A illustrates that TB001 treatment reduced microglial area in the hippocampus of APPSwe mice. FIG. 18B illustrates quantification of microglia in WT mice, MOPC21 and TB001 treated mice. FIG. 18C illustrates that TB001 treatment reduced microglial area in the striatum and thalamus of pMCAO-induced ischemic stroke mice. FIG. 18D illustrates quantification of microglia in WT mice, MOPC and TB001 treated mice.

[0047] In addition to the features described above, additional features and variations will be readily apparent from the following descriptions of the drawings and exemplary embodiments. It is to be understood that these drawings depict typical embodiments and are not intended to be limiting in scope. DETAILED DESCRIPTION

[0048] Some embodiments herein relate to methods of treating or reducing the development of a neurodevelopmental disorder. Although embodiments herein may be exemplified with respect to ASD and ADHD, these are only exemplary embodiments. Other embodiments disclosed herein may be used to treat or reduce development or associated symptoms of other neurodevelopmental disorders as provided herein. For example, some embodiments herein relate to methods of treating or reducing the development a condition or conditions affecting the brain and neurological system of a subject. In some embodiments, the neurodevelopmental disorder can have one or more of a physical cause, such as physical trauma, biological trauma (e.g. infection), chemical trauma (e.g. toxins or drugs), complications during pregnancy and / or exposure to factors during pregnancy, including diet, smoking, toxins, obesity, age, gestational mellitus, allergic diseases, infections, genetics (e.g., mutations in PTEN, MECP2, Galectein-3 and / or ATG7), environmental factors (e.g., air pollutants), immune system dysfunction and many other causes. In some embodiments, the neurodevelopmental disorder(s) is caused by the effect ofmicroglia activation in multiple brain regions of the subjects. In some embodiments, the neurodevelopmental disorder(s) is caused by aberrant synaptic pruning. In some embodiments, microglia are involved in aberrant synaptic pruning. In some embodiments, the neurodevelopmental disorder(s) is caused by increased dendritic spine density and decreased developmental spine pruning of pyramidal neurons. Non-limiting examples of neurodevelopmental disorders include autism spectrum disorder (ASD), Attention- deficit / hyperactivity disorder (ADHD), Intellectual disability (ID), Cerebral palsy, Communication Disorders, Neurodevelopmental Motor Disorders, including Tic Disorders, Specific Learning Disorders or otherwise known by a person skilled in the art.

[0049] Some embodiments herein relate to methods of treating or reducing the development of an autism spectrum disorder (ASD) or associated symptoms thereof in a subject in need thereof. In some embodiments, the methods comprise identifying a subject as having or being at risk of having ASD or associated symptoms thereof and administering an anti-Gal3 antibody or a binding fragment thereof to the subject, wherein administration of the anti-Gal3 antibody treats and / or reduces the development of ASD or associated symptoms thereof in the subject. In some embodiments the anti-Gal3 antibody is an anti-Gal3 antibody or fragment thereof as described herein. In some embodiments the anti-Gal3 antibody comprises TB006, or a fragment thereof.

[0050] Some embodiments herein relate to methods of reducing and / or inhibiting the activity of Galectin-3 (Gal3) in a subject with an autism spectrum disorder (ASD) or associated symptoms thereof. In some embodiments, the methods comprise identifying a subject as having ASD or associated symptoms thereof and administering an anti-Gal3 antibody or a binding fragment thereof to the subject, wherein administration of the anti-Gal3 antibody reduces and / or inhibits the activity of Gal3 in the subject as compared to the activity of the Gal3 in the subject prior to administration of the anti-Gal3 antibody. In some embodiments the anti-Gal3 antibody is an anti-Gal3 antibody or fragment thereof as described herein. In some embodiments the anti-Gal3 antibody comprises TB006, or a fragment thereof.

[0051] Some embodiments herein relate to methods of treating or reducing the development of an attention deficit hyperactivity disorder (ADHD) or associated symptoms thereof in a subject in need thereof. In some embodiments, the methods comprise identifying a subject as having or being at risk of having ADHD or associated symptoms thereof andadministering an anti-Gal3 antibody or a binding fragment thereof to the subject, wherein administration of the anti-Gal3 antibody treats and / or reduces the development of ADHD or associated symptoms thereof in the subject. In some embodiments the anti-Gal3 antibody is an anti-Gal3 antibody or fragment thereof as described herein. In some embodiments the anti-Gal3 antibody comprises TB006, or a fragment thereof. Some embodiments herein relate to a method of reducing and / or inhibiting the activity of Galectin-3 (Gal3) in a subject with an attention deficit hyperactivity disorder (ADHD) or associated symptoms thereof. In some embodiments, the method comprises identifying a subject as having ADHD or associated symptoms thereof and administering an anti-Gal3 antibody or a binding fragment thereof to the subject, wherein administration of the anti-Gal3 antibody reduces the level of Gal3 in the subject as compared to the activity of the Gal3 in the subject prior to administration of the anti-Gal3 antibody. In some embodiments the anti-Gal3 antibody is an anti-Gal3 antibody or fragment thereof as described herein. In some embodiments the anti-Gal3 antibody comprises TB006, or a fragment thereof. Definitions

[0052] In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and 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 will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.

[0053] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the claimed subject matter belongs. It is to 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.

[0054] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0055] The articles “a” and “an” are used herein to refer to one or to more than one (for example, at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0056] By “about” is meant a quantity, level, value, number, 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% to a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length.

[0057] Throughout this specification, unless the context requires otherwise, the words “comprise,” “comprises,” and “comprising” will be understood to imply the inclusion of a stated step or element or group of steps or elements but not the exclusion of any other step or element or group of steps or elements. By “consisting of” is meant 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 no other elements may be present. By “consisting essentially of” is meant including any elements listed after the phrase and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase “consisting essentially of” indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they materially affect the activity or action of the listed elements.

[0058] As used herein, the terms “individual(s)”, “subject(s)” and “patient(s)” mean any mammal. In some embodiments, the mammal is a human. In some embodiments, the mammal is a non-human. None of the terms require or are limited to situations characterized by the supervision (e.g. constant or intermittent) of a health care worker (e.g. a doctor, a registered nurse, a nurse practitioner, a physician’s assistant, an orderly or a hospice worker).

[0059] 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 comprise modified amino acids, and it may be interrupted by non-amino acids. The terms also encompass amino acid polymers that have been modified, for example, via sulfation, glycosylation, lipidation, acetylation, phosphorylation, iodination, methylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, transfer-RNA mediated addition of amino acids to proteins such as arginylation, ubiquitination, or any other manipulation, such as conjugation with a labeling component.

[0060] As used herein the term “amino acid” refers to either natural and / or unnatural or synthetic amino acids, including glycine and both the D or L optical isomers, and amino acid analogs and peptidomimetics.

[0061] A polypeptide or amino acid sequence “derived from” a designated protein refers to the origin of the polypeptide. Preferably, the polypeptide has an amino acid sequence that is essentially identical to that of a 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 which is immunologically identifiable with a polypeptide encoded in the sequence. This terminology also includes a polypeptide expressed from a designated nucleic acid sequence. Peptide sequences having at least 80%, 85%, 90%, 95%, 99%, or 100% homology to any one of the peptide sequences disclosed herein and having the same or similar functional properties are envisioned. The percent homology may be determined according to amino acid substitutions, deletions, or additions between two peptide sequences. Peptide sequences having some percent homology to any one of the peptide sequences disclosed herein may be produced and tested by one skilled in the art through conventional methods. The % homology or % identity of two sequences is well understood in the art and can be calculated by the number of conserved amino acids or nucleotides relative to the length of the sequences.

[0062] As used herein, the term "antibody" denotes the meaning ascribed to it by one of skill in the art, and further it is intended to include any polypeptide chain-containing molecular structure with a specific shape that fits to and recognizes an epitope, where one or more non- covalent binding interactions stabilize the complex between the molecular structure and the epitope. Antibodies utilized in the present invention may be polyclonal antibodies, although monoclonal antibodies are preferred because they may be reproduced by cell culture or recombinantly and can be modified to reduce their antigenicity.

[0063] In addition to entire immunoglobulins (or their recombinant counterparts), immunoglobulin fragments or “binding fragments” comprising the epitope binding site (e.g., Fab', F(ab')2, single-chain variable fragment (scFv), diabody, minibody, nanobody, single-domain antibody (sdAb), or other fragments) are useful as antibody moieties in the present invention. Such antibody fragments may be generated from whole immunoglobulins by ricin, pepsin, papain, or other protease cleavage. Minimal immunoglobulins may be designed utilizing recombinant immunoglobulin techniques. For instance "Fv" immunoglobulins for use in the present inventionmay be produced by linking a variable light chain region to a variable heavy chain region via a peptide linker (e.g., poly-glycine or another sequence which 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, antibodies can be conjugates, e.g. pegylated antibodies, drug, radioisotope, or toxin conjugates. Monoclonal antibodies directed against a specific epitope, or combination of epitopes, will allow for the targeting and / or depletion of cellular populations expressing the marker. Various techniques can be utilized using monoclonal antibodies to screen for cellular populations expressing the marker(s), and include magnetic separation using antibody-coated magnetic beads, "panning" with antibody attached to a solid matrix (i.e., plate), and flow cytometry (e.g. U.S. Pat. No. 5,985,660, hereby expressly incorporated by reference in its entirety).

[0064] As known in the art, the term "Fc region" is used to define a C-terminal region of an immunoglobulin heavy chain. The "Fc region" may be a native sequence Fc region or a variant Fc region. Although the boundaries of the Fc region of an immunoglobulin heavy chain might vary, the human IgG heavy chain Fc region is usually defined to stretch from an amino acid residue at position Cys226, or from Pro230, to the carboxyl-terminus thereof. The numbering of the residues in the Fc region is that of the EU index as in Kabat. Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991. The Fc region of an immunoglobulin generally comprises two constant domains, CH2 and CH3. As is known in the art, an Fc region can be present in dimer or monomeric form.

[0065] As known in the art, a "constant region" of an antibody refers to the constant region of the antibody light chain or the constant region of the antibody heavy chain, either alone or in combination.

[0066] A "variable region" of an antibody refers to the variable region of the antibody light chain or the variable region of the antibody heavy chain, either alone or in combination. As known in the art, the variable regions of the heavy and light chains each consist of four framework regions (FRs) connected by three complementarity determining regions (CDRs) also known as hypervariable regions, and contribute to the formation of the antigen binding site of antibodies. If variants of a subject variable region are desired, particularly with substitution in amino acid residues outside of a CDR region (i.e., in the framework region), appropriate amino acid substitution, preferably, conservative amino acid substitution, can be identified by comparing thesubject variable region to the variable regions of other antibodies which contain CDR1 and CDR2 sequences in the same canonical class as the subject variable region (Chothia and Lesk, J Mol Biol 196(4): 901-917, 1987).

[0067] In certain embodiments, definitive delineation of a CDR and identification of residues comprising the binding site of an antibody is accomplished by solving the structure of the antibody and / or solving the structure of the antibody-ligand complex. In certain embodiments, that can be accomplished by any of a variety of techniques known to those skilled in the art, such as X-ray crystallography. In certain embodiments, various methods of analysis can be employed to identify or approximate the CDR regions. In certain embodiments, various methods of analysis can be employed to identify or approximate the CDR regions. Examples of such methods include, but are not limited to, the Kabat definition, the Chothia definition, the IMGT approach (Lefranc et al., 2003) Dev Comp Immunol. 27:55-77), computational programs such as Paratome (Kunik et al., 2012, Nucl Acids Res. W521-4), the AbM definition, and the conformational definition.

[0068] The Kabat definition is a standard for numbering the residues in an antibody and is typically used to identify CDR regions. See, e.g., Johnson & Wu, 2000, Nucleic Acids Res., 28: 214-8. The Chothia definition is similar to the Kabat definition, but the Chothia definition takes into account positions 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 suite of computer programs produced by Oxford Molecular Group that model antibody structure. See, e.g., Martin et al., 1989, Proc Natl Acad Sci (USA), 86:9268-9272; "AbM.TM., A Computer Program for Modeling Variable Regions of Antibodies," Oxford, UK; Oxford Molecular, Ltd. The AbM definition models the tertiary structure of an antibody from primary sequence using a combination of knowledge databases and ab initio methods, such as those described by Samudrala et al., 1999, "Ab Initio Protein Structure Prediction Using a Combined Hierarchical Approach," in PROTEINS, Structure, Function and Genetics Suppl., 3:194-198. The contact definition is based on an analysis of the available complex crystal structures. See, e.g., MacCallum et al., 1996, J. Mol. Biol., 5:732-45. In another approach, referred to herein as the "conformational definition" of CDRs, the positions of the CDRs may be identified as the residues that make enthalpic contributions to antigen binding. See, e.g., Makabe et al., 2008, Journal of Biological Chemistry, 283:1156-1166. Still other CDR boundary definitions may not strictly follow one of the above approaches, but will nonetheless overlap with at least a portion of theKabat CDRs, although they may be shortened or lengthened in light of prediction or experimental findings that particular residues or groups of residues do not significantly impact antigen binding. As used herein, a CDR may refer to CDRs defined by any approach known in the art, including combinations of approaches. The methods used herein may utilize CDRs defined according to any of these approaches. For any given embodiment containing more than one CDR, the CDRs may be defined in accordance with any of Kabat, Chothia, extended, IMGT, Paratome, AbM, and / or conformational definitions, or a combination of any of the foregoing.

[0069] The term "compete," as used herein with regard to an antibody, means that a first antibody, or an antigen-binding portion thereof, binds to an epitope in a manner sufficiently similar to the binding of a second antibody, or an antigen-binding portion thereof, such that the result of binding of the first antibody with its cognate epitope is detectably decreased in the presence of the second antibody compared to the binding of the first antibody in the absence of the second antibody. The alternative, where the binding of the second antibody to its epitope is also detectably decreased in the presence of the first antibody, can, but need not be the case. That is, a first antibody can inhibit the binding of a second antibody to its epitope without that second antibody inhibiting the binding of the first antibody to its respective epitope. However, where each antibody detectably inhibits the binding of the other antibody with its cognate epitope or ligand, whether to the same, greater, or lesser extent, the antibodies are said to "cross-compete" with each other for binding of their respective epitope(s). Both competing and cross-competing antibodies are encompassed by the present invention. Regardless of the mechanism by which such competition or cross-competition occurs (e.g., steric hindrance, conformational change, or binding to a common epitope, or portion thereof), the skilled artisan would appreciate, based upon the teachings provided herein, that such competing and / or cross-competing antibodies are encompassed and can be useful for the methods disclosed herein.

[0070] An antibody that "preferentially binds" or "specifically binds" (used interchangeably herein) to an epitope is a term well understood in the art, and methods to determine such specific or preferential binding are also well known in the art. A molecule is said to exhibit "specific binding" or "preferential binding" if it reacts or associates more frequently, and / or more rapidly, and / or with greater duration and / or with greater affinity with a particular cell or substance than it does with alternative cells or substances. An antibody "specifically binds" or "preferentially binds" to a target if it binds with greater affinity, and / or avidity, and / or more readily, and / or withgreater duration than it binds to other substances. For example, an antibody that specifically or preferentially binds to a CFD epitope is an antibody that binds this epitope with greater affinity, and / or avidity, and / or more readily, and / or with greater duration than it binds to other CFD epitopes or non-CFD epitopes. It is also understood by reading this definition that, for example, an antibody (or moiety or epitope) that specifically or preferentially binds to a first target may or may not specifically or preferentially bind to a second target. As such, "specific binding" or "preferential binding" does not necessarily require (although it can include) exclusive binding. Generally, but not necessarily, reference to binding means preferential binding.

[0071] As used herein, the term “inhibit” has its plain and ordinary meaning as understood in light of the specification and may refer to the reduction, amelioration, prevention or decrease in an expected activity, such as a cellular activity. The reduction or decrease can be by a percentage that is, is about, is at least, is at least about, is not more than, or is not more than about, may be by at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%, or any percentage that is within a range defined by any two of the aforementioned values, where a reduction or decrease of 100% indicates a complete inhibition and any lower percentage indicates a partial inhibition. The terms inhibit and delay may not necessarily indicate a 100% inhibition or delay. A partial inhibition, prevention, amelioration, reduction or delay may be realized. The inhibition, prevention, amelioration, reduction or delay of the expected activity may be observed in a direct or indirect way. Non-limiting examples of inhibition as used herein may refer to the reduction, inhibition, amelioration, or prevention of microglial activation in the subjects with ASD and / or ADHD. In some embodiments, the inhibition of microglial activation is observed using staining techniques such as, but not limited to fluorescent staining, silver staining, Coomassie brilliant blue staining or Colloidal Coomassie G-250 staining.

[0072] As used herein, the term “antigen binding molecule” refers to a molecule that comprises an antigen binding portion that binds to an antigen and, optionally, a scaffold or framework portion that allows the antigen binding portion to adopt a conformation that promotes binding of the antigen binding portion or provides some additional properties to the antigen binding molecule. In some embodiments, the antigen is Gal3. In some embodiments, the antigen binding portion comprises at least one CDR from an antibody that binds to the antigen. In some embodiments, the antigen binding portion comprises all three CDRs from a heavy chain of an antibody that binds to the antigen or from a light chain of an antibody that binds to the antigen. Insome embodiments, the antigen binding portion comprises all six CDRs from an antibody that binds to the antigen (three from the heavy chain and three from the light chain). In some embodiments, the antigen binding portion is an antibody fragment.

[0073] Non-limiting examples of antigen binding molecules include antibodies, antibody fragments (e.g., an antigen binding fragment of an antibody), antibody derivatives, and antibody analogs. Further specific examples include, but are not limited to, a single-chain variable fragment (scFv), a nanobody (e.g. VH domain of camelid heavy chain antibodies; VHH fragment, see Cortez-Retamozo et al., Cancer Research, Vol. 64:2853-57, 2004), a Fab fragment, a Fab' fragment, a F(ab')2 fragment, a Fv fragment, a Fd fragment, and a complementarity determining region (CDR) fragment. These molecules can be derived from any mammalian source, such as human, mouse, rat, rabbit, pig, dog, cat, horse, donkey, guinea pig, goat, or camelid. Antibody fragments may compete for binding of a target antigen with an intact antibody and the fragments may be produced by the modification of intact antibodies (e.g. enzymatic or chemical cleavage) or synthesized de novo using recombinant DNA technologies or peptide synthesis. The antigen binding molecule can comprise, for example, an alternative protein scaffold or artificial scaffold with grafted 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 as well as wholly synthetic scaffolds comprising, for example, a biocompatible polymer. See, for example, Korndorfer et al., 2003, Proteins: Structure, Function, and Bioinformatics, Volume 53, Issue 1:121-129 (2003); Roque et al., Biotechnol. Prog. 20:639-654 (2004). In addition, peptide antibody mimetics (“PAMs”) can be used, as well as scaffolds based on antibody mimetics utilizing fibronectin components as a scaffold.

[0074] An antigen binding molecule can also include a protein comprising one or more antibody fragments incorporated into a single polypeptide chain or into multiple polypeptide chains. For instance, antigen binding molecule can include, but are not limited to, a diabody (see, e.g., EP 404,097; WO 93 / 11161; and Hollinger et al., Proc. Natl. Acad. Sci. USA, Vol. 90:6444- 6448, 1993); an intrabody; a domain antibody (single VL or VH domain or two or more VH domains joined by a peptide linker; see Ward et al., Nature, Vol. 341:544-546, 1989); a maxibody (2 scFvs fused to 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); a triabody; a tetrabody; a minibody (scFv fused to CH3 domain; see Olafsen et al., Protein EngDes Sel. , Vol.17:315-23, 2004); a peptibody (one or more peptides attached to an Fc region, see WO 00 / 24782); a linear antibody (a pair of tandem Fd segments (VH-CH1-VH-CH1) which, together with complementary light chain polypeptides, form a pair of antigen binding regions, see Zapata et al., Protein Eng., Vol.8:1057-1062, 1995); a small modular immunopharmaceutical (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).

[0075] In certain embodiments, an antigen binding molecule can have, for example, the structure of an immunoglobulin. An “immunoglobulin” is a tetrameric molecule, with each tetramer comprising two identical pairs of polypeptide chains, each pair having one “light” (about 25 kDa) and one “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 primarily responsible for antigen recognition. The carboxy-terminal portion of each chain defines a constant region primarily responsible for effector function.

[0076] Unless otherwise specified, the complementarity defining regions disclosed herein follow the IMGT definition. In some embodiments, the CDRs can instead by Kabat, Chothia, or other definitions accepted by those of skill in the art.

[0077] It is understood that an antibody with an antibody name described herein can be referred using a shortened version of the antibody name, as long as there are no conflicts with another antibody described herein. For example, F846C.1B2 can also be referred to as 846C.1B2, or 846.1B2. This can also refer to fragments of the antibody (e.g., with the same 1, 3, or 6 CDRs).

[0078] As used herein, the terms “treating” or “treatment” (and as well understood in the art) or reducing the development of a disease or associated symptoms thereof means an approach for obtaining beneficial or desired results in a subject's condition, including clinical results. Beneficial or desired clinical results can include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, diminishment of the extent of a disease, stabilizing (i.e., not worsening) the state of disease, prevention of a disease's transmission or spread, delaying or slowing of disease progression, amelioration or palliation of the disease state, diminishment of the recurrence of disease, and remission, whether partial or total and whether detectable or undetectable. Reduction in the development of a disease or associated symptoms thereof can also mean that the disease or one or more associated symptoms do not increase in the subject after the treatment as compared to the disease or one or more associated symptoms priorto treatment. “Treating” and “treatment” as used herein also include prophylactic treatment. Treatment methods comprise administering to a subject a therapeutically effective amount of an active agent. The administering step may consist of a single administration or may comprise a series of administrations. The compositions are administered to the subject in an amount and for a duration sufficient to treat the subject. The length of the treatment period depends on a variety of factors, such as the severity of the condition, the age and genetic profile of the subject, the concentration of active agent, the activity of the compositions used in the treatment, or a combination thereof. It will also be appreciated that the effective dosage of an agent used for the treatment or prophylaxis may increase or decrease over the course of a particular treatment or prophylaxis regime. Changes in dosage may result and become apparent by standard diagnostic assays known in the art. In some embodiments, chronic administration may be required.

[0079] The terms “effective amount” or “effective dose” as used herein have their plain and ordinary meaning as understood in light of the specification and refer to that amount of a recited composition or compound that results in an observable designated effect. Actual dosage levels of active ingredients in an active composition of the presently disclosed subject matter can be varied so as to administer an amount of the active composition or compound that is effective to achieve the designated response for a particular subject and / or application. The selected dosage level can vary based upon 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 the physical condition and prior medical history of the subject being treated. In some embodiments, a minimal dose is administered, and dose is escalated in the absence of dose-limiting toxicity to a minimally effective amount. Determination and adjustment of an effective dose, as well as evaluation of when and how to make such adjustments, are contemplated herein. In some non-limiting examples, an effective amount or effective dose of a composition or compound may relate to the amount or dose that provides a significant, measurable, or sufficient therapeutic effect towards the treatment of neurodevelopmental disorders, or a symptom thereof, for example ASD or ADHD. In some embodiments, the effective amount or effective dose of a composition or compound may treat, ameliorate, or prevent the progression or development of ASD or ASD, or symptoms thereof.

[0080] The term “administering” includes oral administration, topical contact, administration as a suppository, intravenous, intraperitoneal, intramuscular, intralesional,intrathecal, intranasal, or subcutaneous administration, or the implantation of a slow-release device, e.g., a mini-osmotic pump, to a subject. Administration is by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, e.g., intravenous, intramuscular, intra-arteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc. By “co-administer” it is meant that a first compound described herein is administered at the same time, just prior to, or just after the administration of a second compound described herein.

[0081] As used herein, the term "therapeutic target" refers to a gene or gene product that, upon modulation of its activity (e.g., by modulation of expression, biological activity, and the like), can provide for modulation of the disease phenotype. As used throughout, "modulation" is meant to refer to an increase or a decrease in the indicated phenomenon (e.g., modulation of a biological activity refers to an increase in a biological activity or a decrease in a biological activity).

[0082] As used herein, the term “standard of care”, “gold standard,” “best practice” and “standard therapy” refers to the treatment that is accepted by medical practitioners to be an appropriate, proper, effective, and / or widely used treatment for a certain disease. The standard of care of a certain disease depends on many different factors, including the biological effect of treatment, region or location within the body, patient status (e.g. age, weight, gender, hereditary risks, other disabilities, secondary conditions), toxicity, metabolism, bioaccumulation, therapeutic index, dosage, and other factors known in the art. Determining a standard of care for a disease is also dependent on establishing safety and efficacy in clinical trials as standardized by regulatory bodies such as the US Food and Drug Administration, International Council for Harmonization, Health Canada, European Medicines Agency, Therapeutics Goods Administration, Central Drugs Standard Control Organization, National Medical Products Administration, Pharmaceuticals and Medical Devices Agency, 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 (e.g. PD1 / PDL1 or CTLA4 blockade therapy).

[0083] As used herein, “pharmaceutically acceptable” has its plain and ordinary meaning as understood in light of the specification and refers to carriers, excipients, and / orstabilizers that are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed or that have an acceptable level of toxicity. A “pharmaceutically acceptable” “diluent,” “excipient,” and / or “carrier” as used herein have their plain and ordinary meaning as understood in light of the specification and are intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with administration to humans, cats, dogs, or other vertebrate hosts. Typically, a pharmaceutically acceptable diluent, excipient, and / or carrier is a diluent, excipient, and / or carrier approved by a regulatory agency of a Federal, a state government, or other regulatory agency, or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, including humans as well as non-human mammals, such as cats and dogs. The term diluent, excipient, and / or carrier can refer to a diluent, adjuvant, excipient, or vehicle with which the pharmaceutical formulation is administered. Such pharmaceutical diluent, excipient, and / or carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin. Water, saline solutions and aqueous dextrose and glycerol solutions can be employed as liquid diluents, excipients, and / or carriers, particularly for injectable solutions. Suitable pharmaceutical diluents and / or excipients include sugars, starch, glucose, fructose, lactose, sucrose, maltose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, salts, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. A non-limiting example of a physiologically acceptable carrier is an aqueous pH buffered solution. The physiologically acceptable carrier may also comprise one or more of the following: antioxidants, such as ascorbic acid, low molecular weight (less than about 10 residues) polypeptides, proteins, such as serum albumin, gelatin, immunoglobulins, hydrophilic polymers such as polyvinylpyrrolidone, amino acids, carbohydrates such as glucose, mannose, or dextrins, chelating agents such as EDTA, sugar alcohols such as glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, isomalt, maltitol, or lactitol, salt-forming counterions such as sodium, and nonionic surfactants such as TWEEN®, polyethylene glycol (PEG), and PLURONICS®. The formulation, if desired, can also contain minor amounts of wetting, bulking, emulsifying agents, or pH buffering agents. These formulations can take the form of solutions, suspensions, emulsion, sustained release formulations and the like. The formulation should suit the mode of administration.

[0084] Additional excipients with desirable properties include but are not limited to preservatives, adjuvants, stabilizers, solvents, buffers, diluents, solubilizing agents, detergents, surfactants, chelating agents, antioxidants, alcohols, ketones, aldehydes, ethylenediaminetetraacetic acid (EDTA), tris(hydroxymethyl)aminomethane (Tris), citric acid, ascorbic acid, acetic acid, salts, phosphates, citrates, acetates, succinates, chlorides, bicarbonates, borates, sulfates, sodium chloride, sodium bicarbonate, sodium phosphate, sodium borate, sodium citrate, potassium chloride, potassium phosphate, magnesium sulfate sugars, dextrose, dextran 40, fructose, mannose, lactose, trehalose, galactose, sucrose, sorbitol, mannitol, cellulose, serum, amino acids, alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, polysorbate 20, polysorbate 40, polysorbate, 60, polysorbate 80, poloxamer, poloxamer 188, sodium deoxycholate, sodium taurodeoxycholate, magnesium stearate, octylphenol ethoxylate, benzethonium chloride, thimerosal, gelatin, esters, ethers, 2-phenoxyethanol, urea, or vitamins, or any combination thereof. Some excipients may be in residual amounts or contaminants from the process of manufacturing, including but not limited to serum, albumin, ovalbumin, antibiotics, inactivating agents, formaldehyde, glutaraldehyde, β- propiolactone, gelatin, cell debris, nucleic acids, peptides, amino acids, or growth medium components or any combination thereof. The amount of the excipient may be found in the formulation at a percentage that is, is about, is at least, is at least about, is not more than, or is not more than about, 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 100% w / w or any percentage by weight in a range defined by any two of the aforementioned numbers.

[0085] The term “purity” of any given substance, compound, or material as used herein refers to the actual abundance of the substance, compound, or material relative to the expected abundance. For example, the substance, compound, or material may be at least 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% pure, including all decimals in between. Purity may be affected by unwanted impurities, including but not limited to side products, isomers, enantiomers, degradation products, solvent, carrier, vehicle, or contaminants, or any combination thereof. Purity can be measured technologies including but not limited to chromatography, liquid chromatography, gas chromatography, spectroscopy, UV-visible spectrometry, infraredspectrometry, mass spectrometry, nuclear magnetic resonance, gravimetry, or titration, or any combination thereof.

[0086] The term “pharmaceutically acceptable salts” has its plain and ordinary meaning as understood in light of the specification and includes relatively non-toxic, inorganic and organic acid, or base addition salts of compositions or excipients, including without limitation, analgesic agents, therapeutic agents, other materials, and the like. Examples of pharmaceutically acceptable salts include those derived from mineral acids, such as hydrochloric acid and sulfuric acid, and those derived from organic acids, such as ethanesulfonic acid, benzenesulfonic acid, p- toluenesulfonic acid, and the like. Examples of suitable inorganic bases for the formation of salts include the hydroxides, carbonates, and bicarbonates of ammonia, sodium, lithium, potassium, calcium, magnesium, aluminum, zinc, and the like. Salts may also be formed with suitable organic bases, including those that are non-toxic and strong enough to form such salts. For example, the class of such organic bases may include but are not limited to mono-, di-, and trialkylamines, including methylamine, dimethylamine, and triethylamine; mono-, di-, or trihydroxyalkylamines including mono-, di-, and triethanolamine; amino acids, including glycine, arginine and lysine; guanidine; N-methylglucosamine; N-methylglucamine; L-glutamine; N-methylpiperazine; morpholine; ethylenediamine; N-benzylphenethylamine; trihydroxymethyl aminoethane.

[0087] As used herein, the terms “physical” or “physical examination” may refer to assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems, assessments of the abdomen (liver and spleen), and / or height and weight measurements. In some embodiments a physical examination comprises one or more of the preceding assessments. It will be understood that term contemplates any assessment commonly understood to be part of a physical examination. It will be understood that term contemplates any assessment commonly understood to be part of a neurological examination.

[0088] As used herein, the term “vital signs” refers to temperature, oral temperature, skin temperature, heart rate, respiratory rate, blood pressure, and orthostatic blood pressure, or any assessment or measurement commonly understood to be a measure of a subject or patient’s vitality.

[0089] As used herein, the term “disability” means a substantial disruption of a person’s ability to conduct normal life functions.

[0090] The term “% w / w” or “% wt / wt” means a percentage expressed in terms of the weight of the ingredient or agent over the total weight of the composition multiplied by 100.

[0091] As used herein, the term “Synaptic pruning” is an indispensable part of the neuronal maturation process as postnatal development of the Central Nervous System (CNS) includes the excessive generation, selective elimination of synapses, and maturation of surviving neural contacts for the fact that the supernumerary synapses are supposed to be removed to form proper synaptic inputs and to establish mature synaptic architecture.

[0092] As used herein, the term “microglia” refers to a specialized population of macrophage-like cells in the CNS. Microglia are considered immune sentinels that are the primary innate immune effector cells of the CNS. Microglia are also involved in synaptic organization, trophic neuronal support during development, phagocytosis of apoptotic cells in the developing brain, myelin turnover, control of neuronal excitability, phagocytic debris removal as well as brain protection and repair. Activated microglia have been identified surrounding lesions of various neurodegenerative and neurodevelopmental diseases, such as Alzheimer's disease, Parkinson's disease, muscular amyotrophic lateral sclerosis, multiple sclerosis, autism spectrum disorder (ASD) and Attention-deficit / hyperactivity disorder (ADHD).

[0093] As used herein, the term “Neurodevelopmental disorders” refers to a group of conditions affecting the brain and neurological system of a patient. A neurodevelopmental disorder can have one or more of a physical cause, such as physical trauma, biological trauma (e.g. infection), chemical trauma (e.g. toxins or drugs), complications during pregnancy and / or Exposure to factors during pregnancy, including diet, smoking, toxins, obesity, age, gestational mellitus, allergic diseases, infections, genetics (e.g., mutations in PTEN, MECP2, Galectein-3 and / or ATG7), environmental factors (e.g., air pollutants), immune system dysfunction and many other causes. Some neurodevelopmental disorders are caused by the effect of microglia activation in multiple brain regions of the subjects. Some neurodevelopmental disorders are caused by aberrant synaptic pruning. In some neurodevelopmental disorders, microglia are involved in aberrant synaptic pruning. Some neurodevelopmental disorders are caused by increased dendritic spine density and decreased developmental spine pruning of pyramidal neurons. Non-limiting examples of neurodevelopmental disorders include autism spectrum disorder (ASD), Attention- deficit / hyperactivity disorder (ADHD), Intellectual disability (ID), Cerebral palsy, Communication Disorders, Neurodevelopmental Motor Disorders, including Tic Disorders, Specific Learning Disorders or otherwise known by a person skilled in the art.

[0094] As used herein, the term “autism spectrum disorder (ASD)” refers to a heterogeneous neurodevelopmental disorder with life-long consequences. ASD is defined by impairments in social, communication and behavioral challenges. In some embodiments, the corresponding symptoms of ASD, core symptoms of ASD and / or symptoms associated with ASD comprise one or more of impairment in social, communication and interaction skills, restricted or repetitive behaviors or interests, delayed language, movement or learning skills, hyperactivity, impulsive, and / or inattentive behavior, epilepsy or seizure disorder, unusual mood or emotional reactions, anxiety, stress, and / or excessive worry and lack of fear or more fear than expected. In some embodiments, impairment in social, communication and interaction skills comprise one or more of poor eye contact and facial expression, not responding to names, lack of speech or delayed speech, speech with an abnormal tone or rhythm, usage of a singsong voice or robot-like speech, impaired ability to express emotions or feelings and unaware of others’ feelings and / or being passive, aggressive or disruptive. In some embodiments, restricted or repetitive behaviors or interests comprise one or more of performing repetitive movements, performing activities that causes self-harm, getting upset by minor changes, obsessive interests, following certain routines and / or unusual reactions to the way things sound, smell, taste, look or feel.

[0095] Individuals with ASD develop varying degrees of impairments ranging from mild to severe. ASD also includes conditions such as autism, Asperger's syndrome, and childhood disintegrative disorder. ASD is frequently associated with co-occurring language delays. Currently, the only well-accepted treatment for core ASD symptoms is behavior therapy such as Applied Behavioral Analysis (ABA) and Early Intensive Behavioral Intervention. There is no United States (US) Food and Drug Administration (FDA) approved medical therapy that addresses core ASD symptoms or the pathophysiological processes that underlie ASD.

[0096] As used herein, the term “Attention-deficit / hyperactivity disorder (ADHD),” refers to a neurodevelopmental disorder characterized by one or more of restlessness, hyperactivity, inability to sit still, difficulty following instructions and / or to concentrate. In some embodiments, the corresponding symptoms of ADHD, core symptoms of ADHD and / or symptoms associated with ADHD comprise one or more of impairment in cognitive functions, psychosocial functions and behavioral functions. In some embodiments, the corresponding symptoms of ADHD and / or symptoms associated with ADHD comprise one or more of inattentiveness, hyperactivity, impulsivity, disorganization or forgetfulness, learning difficulties and language disorders. ADHDcan be classified into three types based on the symptoms. Predominantly Inattentive Presentation (ADHD-PI) or attention deficit disorder (ADD) is a type of ADHD that is characterized by inattention in the patients. Predominantly Hyperactive-Impulsive Presentation (ADHD-HI) is a type of ADHD that is characterized by symptoms of impulsivity or hyperactivity. Combined Presentation (ADHD-C) is a type of ADHD that can be characterized as a combination of ADHD- PI and ADHD-PI where the subjects exhibit symptoms of inattention, impulsivity and hyperactivity.

[0097] There is no one test to determine if someone has ASD and / or ADHD. Diagnosis of ASD and / or ADHD based on a careful medical history, a physical examination, neurologic examination and genetic assessment, communication testing, cognitive testing, developmental screening and / or formal evaluation of the behavior by employing structured autism spectrum tests. Diagnosis of ASD / ADHD is done using the guidelines in the American Psychiatric Association's Diagnostic and Statistical Manual, Fifth edition (DSM-5). The diagnosis can be made by a healthcare provider (e.g., doctor, nurse practitioner), parent, teachers, self or a specialist such as a neurologist, psychometrician, psychiatrist, psychologist or geriatrician. ASD can be diagnosed or assessed, for example and without limitation, by the Childhood Autism Rating Scale-2 (CARS) and Ohio Autism Clinical Impressions Scale (OACIS), Autism Diagnostic Observation Schedule (ADOS-2), Autism Diagnostic Interview-Revised (ADI-R), ABC-Social Withdrawal subscale, SRS-Social Communication Index Summary Scale, VABS Social Subscale and change ABC- Stereotypies, SRS-Repetitive Behavior Index or other methods known by a person skilled in the art. ADHD can be diagnosed or assessed by, for example and without limitation, Conners Rating Scales, Vanderbilt ADHD Rating Scales, Tests of Variable Attention (TOVA), ADHD Rating Scale-IV (ADHD-RS-IV), Adult ADHD Self-Report Scale (ASRS), Adult ADHD Self-Report Scale (ASRS) Screener, Brown Attention-Deficit Disorder Symptom Assessment Scale (BADDS) for Adults, ADHD Rating Scale IV (ADHD-RS-IV) With Adult Prompts or other methods known by a person skilled in the art. In some embodiments, diagnosis of ASD and / or ADHD include a blood test, an ultrasound, an MRI, and CT scans. The appropriate diagnosis or assessment of ASD and / or ADHD can be chosen depending on the age of the patient, for example, if the patient is a child, teen or adult. In some embodiments, a child is around 0-6 years old, teen is around 6-18 years old and an adult is 18-120 years old.

[0098] As used herein, the term “positron emission tomography” (PET) imaging refers to a versatile nuclear medicine technique to investigate the expression of molecular targets noninvasively. PET imaging tracks the spatial distribution of a positron-emitting radionuclide that is typically conjugated to a targeting molecule. The radioligands [11C]PIB and [18F]florbetaben have been widely used to trace Aβ aggregation in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Furthermore, radioligands targeting translocator protein (TSPO) for PET imaging, such as [18F]GE180 and [11C]ER176, are employed to detect neuroinflammation in neurodegenerative diseases. Antibody-based PET imaging has been extensively studied in oncology in decades. In neurodegenerative diseases, scientists developed radiolabeling of monoclonal antibodies (mAbs) with positron emitters for PET imaging to study the molecule biodistribution and related therapeutics.

[0099] As used herein, the term “MRI” refers to a procedure that uses radio waves, a powerful magnet, and a computer to make a series of detailed pictures of areas inside the body. A contrast agent, such as gadolinium, may be injected into a vein to help the tissues and organs show up more clearly in the picture. MRI may be used to help diagnose disease, plan treatment, or find out how well treatment is working. It is especially useful for imaging the brain and spinal cord, the heart and blood vessels, the bones, joints, and other soft tissues, the organs in the pelvis and abdomen, and the breast. Also called magnetic resonance imaging, NMRI, and nuclear magnetic resonance imaging.

[0100] As used herein, the term “computed tomography scan” (CT scan) refers to a procedure that uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create 3- dimensional (3-D) views of tissues and organs. A dye may be injected into a vein or swallowed to help the tissues and organs show up more clearly. A CT scan may be used to help diagnose disease, plan treatment, or find out how well treatment is working. Also called CAT scan, computed tomography scan, computerized axial tomography scan, and computerized tomography.

[0101] The brain has many distinct regions, each of which is responsible for different functions (for example, memory, judgment and movement). When cells in a particular region are damaged, that region cannot carry out its functions normally.

[0102] As used herein, the terms “physical” or “physical examination” may refer to assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems,assessments of the abdomen (liver and spleen), and / or height and weight measurements. In some embodiments a physical examination comprises one or more of the preceding assessments. It will be understood that term contemplates any assessment commonly understood to be part of a physical examination. It will be understood that term contemplates any assessment commonly understood to be part of a neurological examination.

[0103] As used herein, the term “neurological examination” may assess mental status, motor and sensory skills, hearing and speech, vision, coordination, and balance.

[0104] As used herein, the term “vital signs” refers to temperature, oral temperature, skin temperature, heart rate, respiratory rate, blood pressure, and orthostatic blood pressure, or any assessment or measurement commonly understood to be a measure of a subject or patient’s vitality.

[0105] As used herein, the term “adverse event” refers to any untoward medical occurrence in a clinical study / patient, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention.

[0106] As used herein, the term “unsolicited AE” refers to an AE that was not solicited using a patient diary and that is communicated by a patient / patient’s parent(s) / legally authorized representative (LAR) who has signed the informed consent. Unsolicited AEs include serious and nonserious AEs. Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses requiring a hospitalization, emergency room visit, or visit to / by a healthcare provider). The patients / patient’s parent(s) / LAR(s) is instructed to contact the site as soon as possible to report medically attended event(s), as well as any events that, though not medically attended, are of patient / patient’s parent(s) / LAR(s) concern. Detailed information about reported unsolicited AEs is collected by qualified site personnel and documented in the patient’s records.

[0107] Unsolicited AEs that are not medically attended nor perceived as a concern by the patient / patient’s parent(s) / LAR(s) are collected during an interview with the patients / patient’s parent(s) / LAR(s) and by review of available medical records at the next visit.

[0108] As used herein, the term “solicited AE” refers to predefined local at the injection site and systemic events for which the patient is specifically questioned, and which are noted by the patient in their diary.

[0109] Events meeting the definition of AE include any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs measurements), including those that worsen from baseline, considered clinically significant in the medical and scientific judgment of the investigator (i.e., not related to progression of underlying disease, or more severe than expected for the patient’s condition). Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency and / or intensity of the condition. New condition detected or diagnosed after administration of a pharmaceutical or therapeutic even though it may have been present before the start of the administration. Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or a concomitant medication. Overdose per se is not considered itself as an AE / Serious Adverse Event (SAE) unless it is an intentional overdose taken with possible suicidal / self- harming intent.

[0110] Events not Meeting the AE Definition include any clinically significant abnormal laboratory findings or other abnormal safety assessments that are associated with the underlying disease, unless judged to be more severe than expected for the patient’s condition. The disease / disorder being studied or expected progression, signs, or symptoms of the disease / disorder being studied, unless more severe than expected for the patient’s condition. Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to the procedure is the AE. Situations in which an untoward medical occurrence did not occur (social and / or convenience admission to a hospital). Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at the start of the study that do not worsen.

[0111] As used herein the term “serious adverse event” (SAE) refers to any untoward medical occurrence that, at any dose, results in death or is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization. In general, hospitalization signifies that the patient has been admitted (usually involving at least an overnight stay) at the hospital or emergency ward for observation and / or treatment that would not have been appropriate in the physician’s office or outpatient setting. Complications that occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as to whether hospitalization occurred or was necessary, the AE should be considered serious. Hospitalization for elective treatment of a pre-existing condition that did notworsen from baseline is not considered an AE. Results in persistent or significant disability / incapacity are a SAE. Congenital anomaly / birth defects are SAEs. This definition is not intended to include experiences of relatively minor medical significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (e.g., sprained ankle) that may interfere with or prevent everyday life functions but do not constitute a substantial disruption.

[0112] Other situations that may be considered a SAE include, but are not limited to, important medical events that that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. These events should usually be considered serious. Examples of such events include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions not resulting in hospitalization, or development of intervention dependency or intervention abuse.

[0113] As used herein, the term “life threatening” refers to an event in which the patient was at risk of death at the time of the event. It does not refer to an event, which hypothetically might have caused death, if it were more severe.

[0114] The intensity for each AE and SAE may be assessed based on a grading of Grade 1 through Grade 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) (e.g., preparing meals, shopping for groceries or clothes, using the telephone, managing money). Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL (e.g., bathing dressing and undressing, feeding self, using the toilet, taking medications). An AE that is assessed as severe should not be confused with an SAE. Severe is a category utilized for rating the severity of an event; and both AEs and SAEs can be assessed as severe. An event is defined as “serious” when it meets at least 1 of the predefined outcomes as described in the definition of an SAE, NOT when it is rated as severe. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

[0115] As used herein, the term “interventional trial” refers to a trial designed to find out more about a particular intervention, or treatment. In some embodiments, people taking part inan interventional trial are put into different treatment groups. In some embodiments, a computer puts people taking part in an interventional trial are put into different treatment groups.

[0116] As used herein, the term “observational studies” refers to studies designed to find out what happens to people in different situations. The research team observes the people taking part, but they don’t influence what treatments people have. The people taking part aren’t put into treatment groups.

[0117] As used herein, the term “feasibility studies” refers to studies that are designed to see if it is possible to do the main study. They aim to find out things such as whether patients and doctors are happy to take part, and how long it might take to collect and analyze the information. They don’t answer the main research question about how well a treatment works.

[0118] As used herein, the term “pilot study” refers to small versions of the main study. Pilot studies help to test that all the main parts of the study work together. They may also help answer the research question. Sometimes the research team include the information collected during the pilot study in the results of the main study.

[0119] As used herein, the term “prevention trials” refers to trials that look at whether a particular treatment can help prevent one or more diseases. These trials can be for the general population or for people who have a higher-than-normal risk of developing a certain disease.

[0120] As used herein, the term “screening trials” refers to trails that test people for the early signs of one or more diseases before they have any symptoms. As with prevention trials, screening trials can be for the general population. Or they can be for a group of people who have a higher than normal risk of developing a certain disease. Researchers may plan screening trials to see if new tests are reliable enough to detect particular diseases. Or they may try to find out if there is an overall benefit in detecting the disease early.

[0121] As used herein, the term “treatment trials” refers to trials designed to find out more about the safety and efficacy of new treatments. Treatment trials are generally ran in stages. These stages are called phases. The early phases aim to find out more about the safety and side effects of a new treatments. Later phases aim to see if a new treatment works better than the current treatment. For trials that compare two or more treatments, subjects are put into a treatment group at random. This is a randomized trial. Randomized trials are the best way to get reliable information about how well a new treatment works.

[0122] As used herein, the term “multi-arm multi-stage” (MAMS) trials refers to trials that have several treatment groups as well as the standard treatment group. Multi-arm multi-stage (MAMS) trials have the same control group all the way through. The other treatment groups can change as the trial goes on. The research team may decide to stop recruiting people to a particular group. The researchers may add new treatment groups as new drugs become available to look at. This means they don’t have to design and launch a brand-new trial each time they want to research a new treatment. So, it helps get results quicker.

[0123] Cohort studies, case control studies and cross-sectional studies are all types of observational studies.

[0124] As used herein, the term “cohort” refers to a group of people.

[0125] As used herein, the term “cohort studies” refers to a study that looks at groups of people. A cohort study may follow the group over a period of time. A research team may recruit people who do not have a certain disease or diseases and collect information about them for a number of years. The researchers see who in the group develops the disease and who doesn’t. They then look to see whether the people who developed the disease had anything in common. Cohort studies are very useful ways of finding out more about risk factors. But they are expensive and time consuming. They can be used when it wouldn’t be possible to test a theory any other way.

[0126] As used herein, the term “case control study” refers to the study of a group of people who have a disease (cases) and a group of people who don't (controls). They then look back to see how many people in each group were exposed to a certain risk factor. Researchers want to make the results as reliable as possible. So, they try to make sure the people in each group have the same general factors such as age or gender.

[0127] As used herein, the term “cross sectional study” refers to a study carried out at one point in time, or over a short period of time. Cross sectional studies aim to determine which subjects have been exposed to a risk factor for a certain disease or disease and who has developed said disease or diseases and determine if there is a link between the risk factor and development of the disease.

[0128] As used herein, the term “disability” means a substantial disruption of a person’s ability to conduct normal life functions.

[0129] As used herein, the term “central nervous system” (CNS) refers to part of the nervous system that consists of the brain and spinal cord.

[0130] As uses herein, the term “Epilepsy Diagnosis” is the history of two or more unprovoked seizures. Patients with a history of epilepsy who have been off of medication without seizures for more than two years do not qualify as active epilepsy.

[0131] As used herein, the term “Autism Diagnostic Observation Schedule (ADOS- 2)” is a 40-minute investigator-based procedure that places an individual in a naturalistic social situation designed to elicit specific social and communication reactions. In some embodiments, ADOS-2 is the gold standard for the diagnosis of ASD with the most evidence and highest sensitivity and specificity. In some embodiments, behaviors are coded in the areas of social communication, social relatedness, play and imagination, and restricted interests and / or repetitive behaviors. In some embodiments, “Autism Diagnostic Interview-Revised (ADI-R) can be used to confirm diagnosis since this instrument is based on an interview based on a history of behaviors consistent with ASD. In some embodiments, ADI-R provides an alternative to the ADOS. The ADI-R may take around 2 hours, and may be conducted in person, remotely or by telemedicine based on the preference of the caregiver. In some embodiments, if the participant has had an ADOS-2 assessment at an appropriately reliable site (as determined by the site investigator) within 6 months of screening or had an ADI-R, these measures may be omitted from the screening procedures. If a previous ADOS-2 or ADI-R will be accepted, the participant’s caregiver must provide the site with the results and interpretation of the assessment.

[0132] As used herein, the term “NIH Toolbox (NIHT) that can be accessed at www.nihtoolbox.org” is used to assess neurobehavioral function across a common metric. Using intuitive apps on an iPad, the NIHT measures (a) Mental processes involved in gaining knowledge and comprehension, such as thinking, knowing, remembering, judging and problem solving; (b) complex physiological motor processes that require the integration of multiple systems, including neural motor and sensory-perceptual systems; and (c) emotional processes including joy, sorrow, or fear. In some embodiments, each assessment is only 3-4 minutes, allowing multiple functions to be tested rapidly without subject fatigue. The NIHT has been used in over 300 clinical trials, including individuals with ASD. In some embodiments, the Pattern Comparison Processing Speed Test (4 min), Flanker Inhibitory Control and Attention Test (3 min), Dimensional Change Card Sort Test (4 min) and the Speeded Matching Test (3 min) is used.

[0133] As used herein, the term “Parent Examiner Social Interaction (PESI)” refers to a structured interaction with the individual that will be used to obtain measures of socialinteractions and expressive language. In some embodiments, this interaction will provide the basis of rating behaviors for the OACIS since the naturalistic interactions will provide a more representative sample of everyday behavior. In some embodiments, the interactions are divided into three conditions, two with the parent and participant alone and one with the examiner and the participant interacting. In the first condition (Attending), the parent sits quietly and watches the participant play and only responds to participant-initiated interactions. In the second condition the parent attempts to interact with the participant by asking the participant to imitate and / or asking the participant questions. In some embodiments, both participant / parent interaction conditions are of 10 minutes duration. For the third condition in which examiner and participant interactions are required, Brief Observation of Social Communication Change (BOSCC) or the Screening Tool for Autism in Toddlers & Young Children (STAT) framework depending on the developmental level of the participant is used.

[0134] As used herein, the term “Medical and Behavior Review” refers to a structured questionnaire form that assists with the elicitation and assessment of health complaints, appetite, sleep, activity level and general health at baseline. In some embodiments, the companion measure, the Adverse Effects Review, is used in follow up visits to monitor and document new events during the trial.

[0135] As used herein, the term “suicidality assessment” refers to the Columbia- Suicide Severity Rating Scale, a questionnaire used for suicide assessment developed by multiple institutions, including Columbia University, with NIMH support. In some embodiments, another standardized scale, the Aberrant Behavior Checklist (ABC), a validated questionnaire that rates symptoms of hyperactivity, irritability, social withdrawal, and stereotypic behavior in individuals with developmental disabilities is used. In some embodiments, ABC has convergent and divergent validity and has been used in multiple autism clinical trials. In some embodiments, ABC provides indication of self-harm and self-injury, will be used to monitor self-harm behavior. Any patient with self-harm behavior will not be entered into the trial. The clinician will ask about self-harm at each visit to ensure no such behavior is emerging.

[0136] As used herein, the term “Childhood Autism Rating Scale-2 (CARS)” refers to a clinical rating scale for the trained clinician which uses 15 items specific to ASD characteristics, rated on a 4-point scale of severity, which has been used in many clinical trials as the primary outcome and has been recommended by the EMA Guideline on the clinical development ofmedicinal products as an outcome for ASD clinical trials. In some embodiments, a consensus estimates of the minimal important clinical difference (MCID) is recommended. It is completed after direct observation of the individual with ASD as well as interviewing the characters. The form is used with individuals of all ages and in both clinical and research settings. There are two versions, the standard form (VABC <80) and the high functioning form (VABC >=80). The same form will be used to assess the individuals at the beginning and end of the study. Raters will be calibrated at the beginning of the study on case vignettes.

[0137] As used herein, the term “Clinical Global Impression - Severity (CGI-S) and Improvement (CGI-I)” is a 7-item scale ranging from a score of 1 for “Normal” to 7 for “Extreme” and is a standard outcome measures used in most clinical trials on individuals with ASD. All aspects of the participant’s condition need to be integrated to assign the CGI-S score. Only participants of CGI-S of 4 (“moderate”) or greater severity will be included in the trial but individuals with “Extreme” disease (CGI-S=7) will be excluded. The CGI-S standard version will be completed at screening to determine inclusion. CGI-S will be rated by an assessor who is blind to treatment assignment. The CGI-I is a 7-point measure of overall symptomatic change compared to baseline and is a standard outcome measures used in most clinical trials on individuals with ASD.41 Scores range from -3 (Very Much Improved) through 0 (Unchanged) to 3 (Very Much Worse). All aspects of the participant’s condition need to be integrated to assign the CGI-I score. The CGI-I will be rated by an assessor who is blind to treatment assignment.

[0138] As used herein, the term “Ohio State University Clinical Impressions Scale (OACIS)” is a clinical rating of severity and improvement of 10 ASD-related symptoms: social interaction, aberrant / abnormal behavior, repetitive / ritualistic behavior, verbal communication, non-verbal communication, hyperactivity / inattention, anxiety / fears, sensory sensitivities, restricted / narrow interests, autism. Each item is rated on a 7-point scale. The OACIS will be rated by the study physician. The OACIS is sensitive to clinically meaningful changes in ASD symptoms. It was first developed as the Ohio State University (OSU) Autism Rating Scale43 and has been shown to have good inter-rater and cross-cultural reliability, has been successfully used in several ASD clinical trials and has been used in our previous DBPC trial on leucovorin calcium. In validation studies a 0.5-point change was considered clinically meaningful. The rater will used the interaction between the examiner and participant during the Examiner and Parent Social Interaction evaluation as a sample of interactions to assist in rating the OACIS.Exemplary Methods of Use

[0139] In some embodiments, methods of treating or reducing the development of an autism spectrum disorder (ASD) or associated symptoms thereof in a subject in need thereof are disclosed. In some embodiments, the methods comprise identifying a subject as having or being at risk of having ASD or associated symptoms thereof and administering an anti-Gal3 antibody or a binding fragment thereof to the subject. In some embodiments, the administration of the anti-Gal3 antibody treats and / or reduces the development of ASD or one or more associated symptoms thereof in the subject. In some embodiments the anti-Gal3 antibody comprises TB006, or a fragment thereof.

[0140] In some embodiments, administration of an anti-Gal3 antibody reduces the development of autism spectrum disorder (ASD) or one or more associated symptoms thereof in the subject by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to the development of autism spectrum disorder (ASD) or associated symptoms thereof in the subject prior to administration of the anti-Gal3 antibody. In some embodiments the development and / or symptoms of ASD may be assessed by one or more of Childhood Autism Rating Scale-2 (CARS), Ohio Autism Clinical Impressions Scale (OACIS), Autism Diagnostic Observation Schedule (ADOS-2), Autism Diagnostic Interview-Revised (ADI-R), ABC-Social Withdrawal subscale, SRS-Social Communication Index Summary Scale, VABS Social Subscale and change ABC- Stereotypies and SRS-Repetitive Behavior Index. In some embodiments, assessment is done by a blood test, an ultrasound, an MRI, and CT scan. In some embodiments, administration of an anti- Gal3 antibody reduces the development of autism spectrum disorder (ASD) or symptoms thereof in the subject by between about 1-100, 1-75, 1-50, 1-25, 1-10, 1-5, 5-100, 5-75, 5-50, 5-25, 5-10, 10-100, 10-75, 10-50, 10-25, 25-100, 25-75, 25-50, or 50-100%, as compared to the development of autism spectrum disorder (ASD) or symptoms thereof in the subject prior to administration of the anti-Gal3 antibody.

[0141] In some embodiments, the associated symptoms of ASD may comprise one or more of impaired social communication, impaired cognitive skills, impaired social cognitive skills, impaired motor function, impaired attention, or emotional abnormalities. In some embodiments, administration of an anti-Gal3 antibody reduces the development of autism spectrum disorder(ASD) or a measurement of one or more of impairment in social communication, impaired cognitive skills, impaired social cognitive skills, impaired motor function, impaired attention, or emotional abnormalities by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to the development of autism spectrum disorder (ASD) or social communication, impaired cognitive skills, impaired social cognitive skills, impaired motor function, impaired attention, or emotional abnormalities in the subject prior to administration of the anti-Gal3 antibody.

[0142] In some embodiments, the associated symptoms of ASD comprise one or more of impairment in social, communication and interaction skills, restricted or repetitive behaviors or interests, delayed language, movement or learning skills, hyperactivity, impulsive, and / or inattentive behavior, epilepsy or seizure disorder, unusual mood or emotional reactions, anxiety, stress, and / or excessive worry and lack of fear or more fear than expected. In some embodiments, impairment in social, communication and interaction skills comprise one or more of poor eye contact and facial expression, not responding to names, lack of speech or delayed speech, speech with an abnormal tone or rhythm, usage of a singsong voice or robot-like speech, impaired ability to express emotions or feelings and unaware of others’ feelings and / or being passive, aggressive or disruptive. In some embodiments, restricted or repetitive behaviors or interests comprise one or more of performing repetitive movements, performing activities that causes self-harm, getting upset by minor changes, obsessive interests, following certain routines and / or unusual reactions to the way things sound, smell, taste, look or feel.

[0143] In some embodiments, administration of an anti-Gal3 antibody reduces the development of autism spectrum disorder (ASD) or one or more corresponding impairments in social, communication and interaction skills, restricted or repetitive behaviors or interests, delayed language, movement or learning skills, hyperactivity, impulsive, and / or inattentive behavior, epilepsy or seizure disorder, unusual mood or emotional reactions, anxiety, stress, or excessive worry and lack of fear or more fear than expected by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to the development of autism spectrum disorder (ASD) or the corresponding impairments in social, communication and interaction skills, restricted or repetitive behaviors or interests, delayed language, movement or learning skills, hyperactivity, impulsive,and / or inattentive behavior, epilepsy or seizure disorder, unusual mood or emotional reactions, anxiety, stress, or excessive worry and lack of fear or more fear in the subject prior to administration of the anti-Gal3 antibody. For example, in some embodiments, administration of an anti-Gal3 antibody reduces the development of autism spectrum disorder (ASD) or impairment in social, communication and interaction skills, restricted or repetitive behaviors or interests, delayed language, movement or learning skills, hyperactivity, impulsive, and / or inattentive behavior, epilepsy or seizure disorder, unusual mood or emotional reactions, anxiety, stress, or excessive worry and lack of fear or more fear than expected by between about 1-100, 1-75, 1-50, 1-25, 1-10, 1-5, 5-100, 5-75, 5-50, 5-25, 5-10, 10-100, 10-75, 10-50, 10-25, 25-100, 25-75, 25-50, or 50-100%, as compared to the development of autism spectrum disorder (ASD) or impairment in social, communication and interaction skills, restricted or repetitive behaviors or interests, delayed language, movement or learning skills, hyperactivity, impulsive, and / or inattentive behavior, epilepsy or seizure disorder, unusual mood or emotional reactions, anxiety, stress, or excessive worry and lack of fear or more fear in the subject prior to administration of the anti-Gal3 antibody. In some embodiments, the reduction in the development of ASD or associated symptoms thereof means, that the autism spectrum disorder (ASD) or one or more corresponding impairments do not increase in the subject after the administration of the anti-Gal3 antibody as compared to the ASD or one or more corresponding impairments prior to administration of the anti-Gal3 antibody.

[0144] In some embodiments, administration of an anti-Gal3 antibody inhibits or reduces microglial activation in one or more brain regions of the subjects with ASD by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to the microglia activation in multiple brain regions in the subject prior to administration of the anti-Gal3 antibody. In some embodiments, administration of an anti-Gal3 antibody inhibits or reduces microglia activation in multiple brain regions of the subjects with ASD by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to microglia activation in multiple brain regions in the subject prior to administration of the anti-Gal3 antibody

[0145] In some embodiments, administration of an anti-Gal3 antibody inhibits or reduces aberrant synaptic pruning of the subjects with ASD by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by anytwo of the preceding numbers, as compared to the synaptic pruning in the subjects with ASD prior to administration of the anti-Gal3 antibody.

[0146] In some embodiments, administration of an anti-Gal3 antibody reduces dendritic spine density and increases developmental spine pruning of pyramidal neurons in the subjects with ASD by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to the dendritic spine density subjects and developmental spine pruning of pyramidal neurons in the subjects with ASD prior to administration of the anti-Gal3 antibody.

[0147] In some embodiments, administration of an anti-Gal3 antibody alters the expression of one or more cytokines. In some embodiments, the cytokines comprise one or more of IL-6, IL-17, IL-1b, TNF-α and BDNF. In some embodiments, expression of one or more cytokines is increased or decreased. In some embodiments, expression of cytokines is increased by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, or is increased by a range that is defined by any two of the preceding values. For example, in some embodiments, expression of one or more cytokines is increased by between about 1% and 95%, 1% and 90%, 1% and 75%, 1% and 50%, 1% and 25%, 5% and 95%, 5% and 90%, 5% and 75%, 5% and 50%, 5% and 25%, 10% and 95%, 10% and 90%, 10% and 75%, 10% and 50%, 10% and 25%, 25% and 95%, 25% and 90%, 25% and 75%, or 25% and 50%. In some embodiments, expression of one or more cytokines is decreased by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, or is decreased by a range that is defined by any two of the preceding values.

[0148] In some embodiments, administration of an anti-Gal3 antibody alters the expression of one or more neurotransmitters. In some embodiments, the neurotransmitters comprise GABA and glutamate. In some embodiments, expression of neurotransmitters is increased or decreased. In some embodiments, expression of neurotransmitters is increased by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, or is increased by a range that is defined by any two of the preceding values. For example, in some embodiments, expression of neurotransmitters is increased by between about 1% and 95%, 1% and 90%, 1% and 75%, 1% and 50%, 1% and 25%, 5% and 95%, 5% and 90%, 5% and 75%, 5% and 50%, 5% and 25%, 10% and 95%, 10% and 90%, 10% and 75%, 10% and 50%, 10% and 25%, 25% and 95%, 25% and 90%, 25% and 75%, or 25% and 50%. In some embodiments,expression of neurotransmitters is decreased by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, or is decreased by a range that is defined by any two of the preceding values.

[0149] In some embodiments, administration of an anti-Gal3 antibody alters the expression of complements. In some embodiments, the complements comprise C3 and C4. In some embodiments, expression of complements is increased or decreased. In some embodiments, expression of complements is increased by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, or is increased by a range that is defined by any two of the preceding values. For example, in some embodiments, expression of complements is increased by between about 1% and 95%, 1% and 90%, 1% and 75%, 1% and 50%, 1% and 25%, 5% and 95%, 5% and 90%, 5% and 75%, 5% and 50%, 5% and 25%, 10% and 95%, 10% and 90%, 10% and 75%, 10% and 50%, 10% and 25%, 25% and 95%, 25% and 90%, 25% and 75%, or 25% and 50%. In some embodiments, expression of complements is decreased by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, or is decreased by a range that is defined by any two of the preceding values.

[0150] In some embodiments, administration of an anti-Gal3 antibody alters the regulation of Trem2 ligand. In some embodiments, expression of Trem2 is upregulated or downregulated. In some embodiments, Trem2 is upregulated by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, or by a range that is defined by any two of the preceding values. For example, in some embodiments, Trem2 is upregulated between about 1% and 95%, 1% and 90%, 1% and 75%, 1% and 50%, 1% and 25%, 5% and 95%, 5% and 90%, 5% and 75%, 5% and 50%, 5% and 25%, 10% and 95%, 10% and 90%, 10% and 75%, 10% and 50%, 10% and 25%, 25% and 95%, 25% and 90%, 25% and 75%, or 25% and 50%. In some embodiments, Trem2 is downregulated by about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95%, or by a range that is defined by any two of the preceding values. For example, in some embodiments, Trem2 is downregulated between about 1% and 95%, 1% and 90%, 1% and 75%, 1% and 50%, 1% and 25%, 5% and 95%, 5% and 90%, 5% and 75%, 5% and 50%, 5% and 25%, 10% and 95%, 10% and 90%, 10% and 75%, 10% and 50%, 10% and 25%, 25% and 95%, 25% and 90%, 25% and 75%, or 25% and 50%.

[0151] In some embodiments, methods of reducing and / or inhibiting the activity of Galectin-3 (Gal3) in a subject with an autism spectrum disorder (ASD) or associated symptomsthereof is disclosed. In some embodiments, the methods comprise identifying a subject as having ASD or associated symptoms thereof and administering an anti-Gal3 antibody or a binding fragment thereof to the subject. In some embodiments, the administration of the anti-Gal3 antibody reduces and / or inhibits the activity of Gal3 in the subject as compared to the activity of the Gal3 in the subject prior to administration of the anti-Gal3 antibody. In some embodiments, administration of an anti-Gal3 antibody reduces and / or inhibits the activity of Galectin-3 (Gal3) in a subject with an autism spectrum disorder (ASD) or associated symptoms thereof in a subject in need thereof by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to the activity of Galectin-3 (Gal3) in a subject with an autism spectrum disorder (ASD) or associated symptoms thereof prior to administration of the anti-Gal3 antibody. For example, in some embodiments, administration of an anti-Gal3 antibody reduces and / or inhibits the activity of Galectin-3 (Gal3) in a subject with an autism spectrum disorder (ASD) or associated symptoms thereof by between about 1-100, 1-75, 1-50, 1-25, 1-10, 1-5, 5-100, 5-75, 5-50, 5-25, 5-10, 10- 100, 10-75, 10-50, 10-25, 25-100, 25-75, 25-50, or 50-100%, as compared to the activity of Galectin-3 (Gal3) in a subject with an autism spectrum disorder (ASD) or associated symptoms thereof prior to administration of the anti-Gal3 antibody.

[0152] In some embodiments, the subject has been diagnosed with ASD or exhibits one or more symptoms thereof. In some embodiments, the subject is at a predisposed risk of developing ASD or associated symptoms thereof. In some embodiments, the subject has ASD or associated symptoms thereof from birth. In some embodiments, the subject develops or developed ASD or associated symptoms thereof during childhood. In some embodiments, the subject does not exhibit any symptoms of ASD. In some embodiments, the subject has other disorders such as ADHD, epilepsy or bipolar disorder.

[0153] In some embodiments, the subject is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, or 130 years old.

[0154] Some embodiments herein relate to methods of treating or reducing the development of an attention deficit hyperactivity disorder (ADHD) or associated symptoms thereof in a subject in need thereof. In some embodiments, the methods comprise identifying a subject as having or being at risk of having ADHD or associated symptoms thereof and administering an anti-Gal3 antibody or a binding fragment thereof to the subject, whereinadministration of the anti-Gal3 antibody treats and / or reduces the development of ADHD or associated symptoms thereof in the subject. In some embodiments the anti-Gal3 antibody comprises TB006, or a fragment thereof.

[0155] In some embodiments, administration of an anti-Gal3 antibody reduces the development of an ADHD or associated symptoms thereof in the subject by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to the development of ADHD or associated symptoms thereof in the subject prior to administration of the anti-Gal3 antibody. In some embodiments the development of ADHD and / or associated symptoms may be assessed by, for example and without limitation, Conners Rating Scales, Vanderbilt ADHD Rating Scales, Tests of Variable Attention (TOVA), ADHD Rating Scale-IV (ADHD-RS-IV), Adult ADHD Self- Report Scale (ASRS), Adult ADHD Self-Report Scale (ASRS) Screener, Brown Attention-Deficit Disorder Symptom Assessment Scale (BADDS) for Adults or ADHD Rating Scale IV (ADHD- RS-IV) With Adult Prompts. For example, in some embodiments, administration of an anti-Gal3 antibody reduces the development of ADHD or associated symptoms thereof in the subject by between about 1-100, 1-75, 1-50, 1-25, 1-10, 1-5, 5-100, 5-75, 5-50, 5-25, 5-10, 10-100, 10-75, 10-50, 10-25, 25-100, 25-75, 25-50, or 50-100%, as compared to the development of ADHD or associated symptoms thereof in the subject prior to administration of the anti-Gal3 antibody.

[0156] In some embodiments, the associated symptoms of ADHD may comprise one or more of impaired cognitive functions, impaired psychosocial functions or impaired behavioral functions. In some embodiments, administration of an anti-Gal3 antibody reduces the development of ADHD or a measurement of one or more of impaired cognitive functions, impaired psychosocial functions and impaired behavioral functions by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to the development of ADHD) or impaired cognitive functions, impaired psychosocial functions and impaired behavioral functions in the subject prior to administration of the anti-Gal3 antibody.

[0157] In some embodiments, the associated symptoms of ADHD comprise one or more of inattentiveness, hyperactivity, impulsivity, disorganization or forgetfulness, learning difficulties and language disorders. In some embodiments, administration of an anti-Gal3 antibody reduces the development of ADHD or inattentiveness, hyperactivity, impulsivity, disorganizationor forgetfulness, learning difficulties and language disorders by about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100%, or by an amount in a range that is defined by any two of the preceding numbers, as compared to the development of ADHD or inattentiveness, hyperactivity, impulsivity, disorganization or forgetfulness, learning difficulties and language disorders in the subject prior to administration of the anti-Gal3 antibody. For example, in some embodiments, administration of an anti-Gal3 antibody reduces the development of ADHD or inattentiveness, hyperactivity, impulsivity, disorganization or forgetfulness, learning difficulties and language disorders than expected by between about 1-100, 1-75, 1-50, 1-25, 1-10, 1-5, 5-100, 5-75, 5-50, 5-25, 5-10, 10-100, 10-75, 10-50, 10-25, 25-100, 25-75, 25-50, or 50-100%, as compared to the development of ADHD or inattentiveness, hyperactivity, impulsivity, disorganization or forgetfulness, learning difficulties and language disorders in the subject prior to administration of the anti-Gal3 antibody. In some embodiments, the reduction in the development of ASDHD or associated symptoms thereof means, that the ADHD or one or more corresponding impairments do not increase in the subject after the administration of the anti-Gal3 antibody as compared to the ADHD or one or more corresponding impairments prior to administration of the anti-Gal3 antibody.

[0158] Some embodiments herein relate to a method of reducing and / or inhibiting the activity of Galectin-3 (Gal3) in a subject with an attention deficit hyperactivity disorder (ADHD) or associated symptoms thereof. In some embodiments, the method comprises identifying a subject as having ADHD or associated symptoms thereof and administering an anti-Gal3 antibody or a binding fragment thereof to the subject, wherein administration of the anti-Gal3 antibody reduces and / or inhibits the activity of Gal3 in the subject as compared to the activity of the Gal3 in the subject prior to administration of the anti-Gal3 antibody.

[0159] In some embodiments, the subject has been diagnosed with ADHD or symptoms thereof. In some embodiments, the subject is at a predisposed risk of developing ADHD or symptoms thereof. In some embodiments, the subject has ADHD or symptoms thereof from birth. In some embodiments, the subject develops or developed ADHD or symptoms thereof during childhood. In some embodiments, the subject does not exhibit any symptoms of ADHD. In some embodiments, the subject has other disorders such as ASD, epilepsy or bipolar disorder.

[0160] In some embodiments, GAL3 is wild type (WT) GAL3. In some embodiments, GAL3 is a P64H isoform of Gal3 with rs4644 single nucleotide polymorphism. In some embodiments, both alleles of the GAL3 target locus have WT GAL3. In some embodiments, both alleles of the GAL3 target locus have P64H isoform of Gal3 with rs4644 single nucleotide polymorphism. In some embodiments, one allele of the GAL3 target locus has P64H isoform of Gal3 with rs4644 single nucleotide polymorphism. In some embodiments, there is one copy of the variant-type allele. In some embodiments, there are two copies of the variant-type allele.

[0161] In some embodiments, detection of reduced activity or inhibited activity of Gal3 is done using one or more of enzyme linked immunosorbent assay (ELISA), immunofluorescence, western blotting, immunodiffusion, polymerase chain reaction (PCR) or flow cytometry.

[0162] In some embodiments, Gal3 activity is detected in a sample obtained from a patient, for example from blood, spleen, bone marrow, tumor or any combination thereof before and after the administration of the anti-Gal3 antibody.

[0163] In some embodiments, the subject is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, or 130 years old.

[0164] In some embodiments the anti-Gal3 antibody is an anti-Gal3 antibody or fragment thereof as described herein. In some embodiments, the anti-Gal3 antibody is TB006 or a comprises a binding fragment thereof.

[0165] In some embodiments, the anti-Gal3 antibody is administered intravenously.

[0166] In some embodiments, the anti-Gal3 antibody is administered intraperitoneally.

[0167] In some embodiments, the anti-Gal3 antibody is administered topically.

[0168] In some embodiments, the anti-Gal3 antibody is administered daily, twice daily, weekly, bi-weekly, monthly, bimonthly, quarterly, and / or yearly.

[0169] In some embodiments, the anti-Gal3 antibody is administered for up to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 weeks, or for an amount of time that is in a range defined by any two of the preceding values. For example, in some embodiments, the anti-Gal3 antibody is administered for between about 1 and 20, 1 and 10, 1 and 8, 1 and 6, 1 and 4, 1 and 2, 1 and 14, 2 and 20, 2 and 10, 2 and 8, 2 and 6, 2 and 4, 4 and 12, 4 and 10, 4 and 8, 4 and 6, 6 and 12, 6 and 10, 6 and 8, 8 and 12, 8 and 10, or 10 and 20 weeks. In some embodiments, the anti-Gal3 antibody is administered for longer than 20 weeks. In some embodiments, the anti-Gal3 antibody is administered on an ongoing basis.

[0170] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3, and a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3; wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 1940, or 1764, the VH-CDR2 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 77, or 1781, the VH-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 118, or 1798, the VL-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 178, or 1815, the VL-CDR2 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 229, or 1831, and the VL-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 256, or 1849.

[0171] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 1 VL-CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs:170-296, or1814-1864.

[0172] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VL-CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs:170-296, or 1814-1864.

[0173] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 1 VH-CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-169, 801, 802, 951- 954, 1763-1813, or 1940.

[0174] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VH-CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-169, 801, 802, 951- 954, 1763-1813, or 1940.

[0175] In some embodiments, the anti-Gal3 antibody comprises at least 1 CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-296, 801, 802, 951- 954, 1763-1813, or 1940.

[0176] In some embodiments, the anti-Gal3 antibody comprises at least 6 CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-296, 801, 802, 951-9541763-1813, or 1940.

[0177] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-70, 1763-1779,or 1940; the VH-CDR2 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 71- 111, 801, 951, 952, or 1780-1796; the VH-CDR3 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NO: 112-169, 802, 953, 954, or 1797-1813; the VL-CDR1 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220 or 1814-1830; the VL-CDR2 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 221-247or 1831-1847; and the VL-CDR3 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 248-296 or 1848-1864.

[0178] In some embodiments, the anti-Gal3 antibody comprises a combination of the VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 as illustrated in FIG. 7.

[0179] In some embodiments, the antibody comprises at least 1 CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220, 221-247, 248-296, 27-70, 71-111, 801, 951-952,112-169, 802, 951-954 ,1763-1864 or 1940.

[0180] In some embodiments, the antibody comprises at least 6 CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220, 221-247, 248-296, 27-70, 71-111, 801, 951-952,112-169, 802, 951-954 , 1763-1864 or 1940.

[0181] In some embodiments, the anti-Gal3 antibody comprises a heavy chain variable region, wherein the heavy chain variable region comprises a sequence having at least 90% identityto the sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 940, 955-968, 1067-1109, 1415-1439 or1882-1898.

[0182] In some embodiments, the anti-Gal3 antibody comprises a light chain variable region, wherein the light chain variable region comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, 1440-1464, 1899-1914 or 1921.

[0183] In some embodiments, the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, 1465-1489 or 1679-1694.

[0184] In some embodiments, the anti-Gal3 antibody comprises a light chain, wherein the light chain comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, 1490-1514 or 1713-1728.

[0185] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 31; the VH-CDR2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 72; the VH-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 113; the VH-CDR1 comprises an amino acid sequence having at least 90%identity to SEQ ID NO: 171; the VH-CDR1 comprises an amino acid sequence having at least 90%identity to SEQ ID NO: 222; and the VH- CDR1 comprises an amino acid sequence having at least 90%, to SEQ ID NO: 249.

[0186] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VH-CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 31, 72, 113, 1940, 77, 118, 1764, 1781 or 1798.

[0187] In some embodiments, the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VH-CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 171, 222, 249, 178, 229, 256, 1815, 1831 or 1849.

[0188] In some embodiments, the anti-Gal3 antibody comprises a heavy chain variable region, wherein the heavy chain variable region comprises a sequence having at least 90% identity to SEQ ID NO: 298, 1067, 814, 1928, 1920 or 1930.

[0189] In some embodiments, the anti-Gal3 antibody comprises a light chain variable region, wherein the light chain variable region comprises a sequence having at least 90% identity to SEQ ID NO: 375, 1110, 829, 1931, 1932 or 1933.

[0190] In some embodiments, the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the SEQ ID NO: 449, 1153, 844, 1934, 1695 or 1935.

[0191] In some embodiments, the anti-Gal3 antibody comprises a light chain, wherein the light chain comprises a sequence having at least 90% identity to SEQ ID NO: 496, 1196, 859, 1936, 1746 or 1937.

[0192] In some embodiments, the anti-Gal3 antibody comprises a heavy chain variable region, wherein the heavy chain variable region comprises a sequence having at least 90% identity to SEQ ID NO: 309.

[0193] In some embodiments, the anti-Gal3 antibody comprises a light chain variable region, wherein the light chain variable region comprises a sequence having at least 90% identity to SEQ ID NO: 387.

[0194] In some embodiments, the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the SEQ ID NO: 462.

[0195] In some embodiments, wherein the anti-Gal3 antibody comprises a light chain, wherein the light chain comprises a sequence having at least 90% identity to SEQ ID NO: 508.

[0196] In some embodiments, the anti-Gal3 antibody 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, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, 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, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6,847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4- HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10- hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, 2D10-VH0-VL0, 2D10-hVH4- HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10- hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or binding fragments thereof.

[0197] In some embodiments, the antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 31; the VH-CDR2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 72; the VH-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 113; the VH-CDR1 comprises an amino acid sequence having at least 90%identity to SEQ ID NO: 170; the VH-CDR1 comprises an amino acid sequence having at least 90%identity to SEQ ID NO: 221; and the VH-CDR1 comprises an amino acid sequence having at least 90%, to SEQ ID NO: 248.

[0198] In some embodiments, the anti-Gal3 antibodies or binding fragments thereof comprise a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3. In some embodiments, the anti-Gal3 antibodies or binding fragments thereof comprise a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3. In some embodiments, the VH-CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs: 27-70, 1763- 1779 or 1940. In some embodiments, the VH-CDR2 comprises an amino acid sequence having atleast 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs: 71-111, 801, 951, 952 or 1780-1796. In some embodiments, the VH- CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs: 112-169, 802, 953, 954 or 1797-1813. In some embodiments, the VL-CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs: 170-220 or 1814-1830. In some embodiments, the VL-CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs: 211-247 or 1831-1847. In some embodiments, the VL-CDR3 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any amino acid sequence according to SEQ ID NOs: 248-296 or 1848-1864. In some embodiments, the antibodies comprise one or more sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a VL sequence, a VH sequence, a VL / VH pairing, and / or VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, VL-CDR3 (including 1, 2, 3, 4, or 5 amino acid substitutions of any one or more of these CDRs) set from the heavy chain and light chain sequences as depicted in FIG. 9.

[0199] In some embodiments, antibodies or binding fragments thereof are provided. In some embodiments, the antibodies or binding fragments thereof are anti-Gal3 antibodies or binding fragments thereof. In some embodiments, the anti-Gal3 antibodies or binding fragments thereof comprises a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3. In some embodiments, the anti-Gal3 antibodies or binding fragments thereof comprise a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3. In some embodiments, the VH-CDR1 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to any amino acid sequence according to SEQ ID NOs: 27-70, 1763-1779 or 1940. In some embodiments, the VH-CDR2 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to any amino acid sequence according to SEQ ID NOs: 71-111, 801, 951, 952 or 1780-1796. In some embodiments, the VH-CDR3 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to any amino acid sequence according to SEQ ID NOs: 112-169, 802, 953, 954 or 1797-1813. In some embodiments, the VL- CDR1 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to any amino acid sequence according to SEQ ID NOs: 170-220 or 1814-1830. In some embodiments, the VL-CDR2 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to any amino acid sequence according to SEQ ID NOs: 211-247 or 1831- 1847. In some embodiments, the VL-CDR3 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions relative to any amino acid sequence according to SEQ ID NOs: 248-296 or 1848-1864.

[0200] In some embodiments, the antibody or binding fragment thereof comprises a combination of a VL-CDR1, a VL-CDR2, a VL-CDR3, a VH-CDR1, a VH-CDR2, and a VH-CDR3 as illustrated in FIG. 7.

[0201] In some embodiments, the antibody or binding fragment thereof comprises a combination of a VH-CDR1, a VH-CDR2, a VH-CDR3, VL-CDR1, a VL-CDR2, and a VL-CDR3, where one or more of these CDRs is defined by a consensus sequence. The consensus sequences provided herein have been derived from the alignments of CDRs depicted in FIG. 16A-B. However, it is envisioned that alternative alignments may be done (e.g. using global or local alignment, or with different algorithms, such as Hidden Markov Models, seeded guide trees, Needleman-Wunsch algorithm, or Smith-Waterman algorithm) and as such, alternative consensus sequences can be derived.

[0202] In some embodiments, the VH-CDR1 is defined by the formula X1X2X3X4X5X6X7X8X9X10(SEQ ID NO.1915), where X1is E, G, or R; X2is F, N, or Y; X3is A, I, K, N, S, or T; X4is F, I, or L; X5is I, K, N, R, S, or T; X6is D, G, I, N, S, or T; X7is F, G, H, S, or Y; X8is no amino acid, A, D, G, I, M, N, T, V, W, or Y; X9is no amino acid, M, or Y; X10is no amino acid or G; In some embodiments, the VH-CDR1 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the VH- CDR1 comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0203] In some embodiments, the VH-CDR2 is defined by the formula X1X2X3X4X5X6X7X8X9X10(SEQ ID NO.1916), where X1is no amino acid, I, or L; X2is no amino acid or R; X3is no amino acid, F, I, L, or V; X4is A, D, F, H, K, L, N, S, W, or Y; X5is A, D, P, S, T, W, or Y; X6is D, E, G, H, K, N, S, V, or Y; X7is D, E, G, N, S, or T; X8is D, G, I, K, N, Q, R, S, V, or Y; X9is A, D, E, G, I, K, N, P, S, T, V, or Y; X10is no amino acid, I, P, S, or T. In some embodiments, the VH-CDR2 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the VH-CDR2 comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0204] In some embodiments, the VH-CDR3 is defined by the formula X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17X18X19X20X21X22X23X24X25(SEQ ID NO. 1917), where X1is no amino acid or A; X2is no amino acid, A, R, or Y; X3is no amino acid, A, F, H, K, L, R, S, or V; X4is no amino acid, A, D, K, N, R, S, or T; X5is no amino acid, A, D, G, H, I, L, N, P, R, S, T, V, or Y; X6is no amino acid, A, D, G, H, K, N, P, Q, R, S, or Y; X7is no amino acid, D, F, G, H, P, R, S, W, or Y; X8is no amino acid, A, D, E, G, I, R, or S; X9is no amino acid, A, C, D, E, F, G, I, N, R, S, T, V, or Y; X10is no amino acid, A, D, M, P, R, S, T, V, or Y; X11is no amino acid, A, D, E, F, L, T, V, or Y; X12is no amino acid, A, G, L, M, R, or T; X13is no amino acid, A, D, E, F, G, R, S, T, or V; X14is no amino acid, A, D, G, L, P, Q, R, S, T, V, or Y; X15is no amino acid, A, D, G, N, S, V, W, or Y; X16is no amino acid, A, D, E, F, L, P, T, V, W, or Y; X17is no amino acid, F, I, L, M, R, or Y; X18is no amino acid, A, D, G, N, or T; X19is no amino acid, F, N, S, T, V, or Y; X20is no amino acid or L; X21is no amino acid or A; X22is no amino acid or W; X23is no amino acid or F; X24is no amino acid or A; X25is no amino acid or Y. In some embodiments, the VH-CDR3 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the VH-CDR3 comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0205] In some embodiments, the VL-CDR1 is defined by the formula X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17(SEQ ID NO. 1918), where X1is no amino acid or R; X2is no amino acid or S; X3is no amino acid, S, or T; X4is no amino acid, E, G, K, Q, or R; X5is no amino acid, A, D, G, I, N, or S; X6is no amino acid, I, L, or V; X7is no amino acid, F, L, S, or V; X8is no amino acid, D, E, H, N, S, T, or Y; X9is no amino acid, D, E, I, K, N, R, S, T, or V; X10is no amino acid, D, H, N, R, S, or Y; X11is no amino acid, A, G, N, S, T, or V; X12is no amino acid, A, I, K, N, Q, T, V, or Y; X13is no amino acid, D, G, H, K, N, S, T, or Y; X14is no amino acid, C, F, I, N, S, T, V, or Y; X15is no amino acid, D, L, N, W, or Y; X16is no amino acid, N, or D; X17is no amino acid or D. In some embodiments, the VL-CDR1 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the VL-CDR1 comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0206] In some embodiments, the VL-CDR2 is defined by the formula X1X2X3X4X5X6X7X8(SEQ ID NO. 1919), where X1is no amino acid, K, L, N, Q, or R; X2is no amino acid, A, L, M, or V; X3is no amino acid, C, K, or S; X4is no amino acid or T; X5is no amino acid, A, E, F, G, H, K, Q, R, S, W, or Y; X6is no amino acid, A, G, or T; X7is no amino acid, I, K, N, S, or T; X8is no amino acid, N, or S. In some embodiments, the VL-CDR2 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the VL-CDR2 comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0207] In some embodiments, the VL-CDR3 is defined by the formula X1X2X3X4X5X6X7X8X9X10(SEQ ID NO. 1920), where X1is no amino acid, A, E, F, H, L, M, Q, S, V, or W; X2is A, H, or Q; X3is D, F, G, H, L, M, N, Q, S, T, W, or Y; X4is no amino acid or W; X5is A, D, I, K, L, N, Q, R, S, T, V, or Y; X6is D, E, H, I, K, L, N, Q, S, or T; X7is D, F, K, L, N, P, S, T, V, W, or Y; X8is H, P, or S; X9is F, L, P, Q, R, T, W, or Y; X10is no amino acid, T, or V. In some embodiments, the VL-CDR3 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, the VL-CDR3 comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0208] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, 1415-1439 or 1882-1898. In some embodiments, the light chain variable region of the antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, 1440-1464, 1899-1914 or 1921. In some embodiments, the antibodies or binding fragments thereof are anti-Gal3 antibodies or binding fragments thereof.

[0209] In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to the sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 955-968, 1067-1109, 1415-1439 or 1882-1898. In some embodiments, the light chain variable region of the antibody or binding fragment thereof comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to the sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969- 982, 1110-1152, 1440-1464, 1899-1914 or 1921. In some embodiments, the antibodies or binding fragments thereof are anti-Gal3 antibodies or binding fragments thereof.

[0210] In some embodiments, the antibodies comprise one or more sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a VL sequence, a VH sequence, a VL / VH pairing, and / or VL-CDR1, VL-CDR2, VL-CDR3, VH-CDR1, VH-CDR2, VH-CDR3 (including 1, 2, 3, 4, or 5 amino acid substitutions of any one or more of these CDRs) set from the heavy chain and light chain sequences as depicted in FIG. 9.

[0211] In some embodiments, the anti-Gal3 antibodies or binding fragments thereof comprises a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3. In some embodiments, the anti-Gal3 antibodies or binding fragments thereof comprise a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3. In some embodiments, the VH-CDR1 comprises one of the amino acid sequences of SEQ ID NOs: 27-70, 1763-1779 or 1940,the VH-CDR2 comprises one of the amino acid sequences of SEQ ID NOs: 71-111, 801, 951, 952 or 1780-1796, the VH-CDR3 comprises one of the amino acid sequences of SEQ ID NO: 112- 169, 802, 953, 954 or 1797-1813, the VL-CDR1 comprises one of the amino acid sequences of SEQ ID NOs: 170-220 or 1814-1830, the VL-CDR2 comprises one of the amino acid sequences of SEQ ID NOs: 221-247 or 1831-1847, the VL-CDR3 comprises one of the amino acid sequences of SEQ ID NOs: 248-296 or 1848-1864, the heavy chain variable region has a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one of the amino acid sequences of SEQ ID NOs: SEQ ID Nos: 297-373, 803, 806-820, 955-968, 1067-1109, 1415-1439 or 1882-1898, and the light chain variable region has a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one of the amino acid sequences of SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110-1152, 1440-1464, 1899-1914 or 1921.

[0212] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983- 996, 1153-1195, 1465-1489 or 1695-1711. In some embodiments, the heavy chain further comprises a signal peptide having at least 90% identity to SEQ ID NO: 1922 or SEQ ID NO: 1923. In some embodiments, the heavy chain further comprises a signal peptide that is SEQ ID NO: 1922. In some embodiments, the light chain further comprises a signal peptide that is SEQ ID NO: 1923. In some embodiments, the antibody or binding fragment thereof comprises a light chain, wherein the light chain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1490- 1514 or 1746-1762. In some embodiments, the light chain further comprises a signal peptide. In some embodiments, the light chain further comprises a signal peptide having at least 90% identity to SEQ ID NO: 1924 or SEQ ID NO: 1925. In some embodiments, the light chain further comprises a signal peptide that is SEQ ID NO: 1924. In some embodiments, the light chain further comprises a signal peptide that is SEQ ID NO: 1925. In some embodiments, the antibodies or binding fragments thereof are anti-Gal3 antibodies or binding fragments thereof.

[0213] In some embodiments, the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain, wherein the heavy chain is encoded by a nucleic acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a sequence selected from SEQ ID NOs: 703- 749, 799, 896-910, 1039-1052, 1325-1367, 1413, or 1565-1589. In some embodiments, the heavy chain further comprises a signal peptide encoded by a nucleic acid sequence having at least 90% identity to SEQ ID NO: 1926 or SEQ ID NO: 1927. In some embodiments, the heavy chain further comprises a signal peptide encoded by a nucleic acid sequence that is SEQ ID NO: 1926. In some embodiments, the light chain further comprises a signal peptide encoded by a nucleic acid sequence that is SEQ ID NO: 1927. In some embodiments, the antibody or binding fragment thereof comprises a light chain, wherein the light chain is encoded by a nucleic acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the sequence selected from SEQ ID NOs: 750- 796, 911-925, 1053-1066, 1368-1410, 1414, or 1590-1614. In some embodiments, the light chain further comprises a signal peptide. In some embodiments, the light chain further comprises a signal peptide encoded by a nucleic acid sequence having at least 90% identity to SEQ ID NO: 1928 or SEQ ID NO: 1929. In some embodiments, the light chain further comprises a signal peptide encoded by a nucleic acid sequence that is SEQ ID NO: 1928. In some embodiments, the light chain further comprises a signal peptide that is SEQ ID NO: 1929.

[0214] In some embodiments, the anti-Gal3 antibodies or binding fragments thereof comprise a heavy chain variable region and a light chain variable region. In some embodiments, the heavy chain variable region is paired with an IgG4 heavy chain constant domain or an IgG2 heavy chain constant domain. In some embodiments, the IgG4 heavy chain constant domain or IgG2 heavy chain constant domain are human or murine. In some embodiments, the IgG4 heavy chain constant domain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 931. In some embodiments, the IgG4 heavy chain constant domain is an S228P mutant. In some embodiments, the IgG2 heavy chain constant domain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 933 or SEQ ID NO: 934. In some embodiments, the IgG2 heavy chain constant domain is a LALAPG or a LALA mutant. Insome embodiments, the light chain variable region is paired with an IgG4 kappa chain constant domain. In some embodiments, the IgG4 kappa chain constant domain comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 932. Exemplary heavy chain and light chain constant domains can be found in FIG. 49. In some embodiments, the light chain variable region and / or heavy chain variable region may be selected from those depicted in FIG. 5 and 6 and / or the combinations of light chain variable region and heavy chain variable region as depicted in FIG. 7.

[0215] In some embodiments, the 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, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, 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, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2- mH0mL2, 847.12C4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10- hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3- VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or 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: 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3- HVL3, 2D10-hVH3-HVL4, or 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: 21H6- H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6- H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6- H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or binding fragment thereof. In some embodiments, the antibody or binding fragment thereof further comprises a signal peptide.

[0216] In some embodiments, the antibody or binding fragment thereof comprises a sequence (e.g. CDR, VL, VH, LC, HC) having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence of TB001, TB006, 12G5.D7, 13A12.2E5, 14H10.2C9, 15F10.2D6, 19B5.2E6, 20D11.2C6, 20H5.A3, 23H9.2E4, 2D10.2B2, 3B11.2G2, 7D8.2D8, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, 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, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4- HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10- hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3-VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, or 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: 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10- hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, or 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: 21H6-H0L0, 21H6-H1L1, 21H6-H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6-H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6-H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6-H6L3, 21H6-H6L4, or binding fragment thereof. In some embodiments, the antibody or binding fragment thereof further comprises a signal peptide.

[0217] In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to specific epitopes within a Gal3 protein. In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to a specific epitope within a Gal3 protein having an amino acid sequence according to SEQ ID NO: 1-2, provided in FIG. 1.

[0218] In some embodiments, the anti-Gal3 antibody or binding fragment thereof may 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 a peptide illustrated in FIG. 2 (SEQ ID NOs: 3-26).

[0219] In some embodiments, the anti-Gal3 antibody or binding fragment thereof may bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within amino acid residues 1-20 of SEQ ID NO: 1-2. In some embodiments, the anti- Gal3 antibody or binding fragment thereof may bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within amino acid residues 31-50 of SEQ ID NO: 1-2. In some embodiments, the anti-Gal3 antibody or binding fragment thereof may bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within amino acid residues 51-70 of SEQ ID NO: 1-2. In some embodiments, the anti-Gal3 antibody or binding fragment thereof may bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within amino acid residues 61-80 of SEQ ID NO: 1- 2.

[0220] In some embodiments, the anti-Gal3 antibody or binding fragment thereof may bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within Peptide 1 (SEQ ID NO: 3), Peptide 4 (SEQ ID NO: 6), Peptide 6 (SEQ ID NO: 8), or Peptide 7 (SEQ ID NO: 9). In some embodiments, the anti-Gal3 antibody or binding fragment thereof may bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within Peptide 1 (SEQ ID NO: 3). In some embodiments, the anti-Gal3 antibody or binding fragment thereof may 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 4 (SEQ ID NO: 6). In some embodiments, the anti-Gal3 antibody or binding fragment thereof may bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within Peptide 6 (SEQ ID NO: 8). In some embodiments, the anti-Gal3 antibody or binding fragment thereof may bind to at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues within Peptide 7 (SEQ ID NO: 9). In some embodiments, the anti-Gal3 antibody or bindingfragment thereof binds to an epitope present within a region of Gal3 defined by Peptide 1 (SEQ ID NO: 3). In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to an epitope present within a region of Gal3 defined by Peptide 4 (SEQ ID NO: 6). In some embodiments, the anti-Gal3 antibody or binding fragment thereof binds to an epitope present within a region of Gal3 defined by Peptide 6 (SEQ ID NO: 8). In some embodiments, the anti- Gal3 antibody or binding fragment thereof binds to an epitope present within a region of Gal3 defined by Peptide 7 (SEQ ID NO: 9). In some embodiments, the antibody is one that binds to 1, 2, or all 3 of peptides 1, 6, and / or 7.

[0221] In some embodiments, the anti-Gal3 antibody or binding fragment thereof further comprises one or more signal peptides. In some embodiments, the anti-Gal3 antibody or binding fragment thereof heavy chain further comprises a signal peptide. In some embodiments, the heavy chain further comprises a signal peptide having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 1922 or SEQ ID NO: 1923. In some embodiments, the heavy chain further comprises a signal peptide that is SEQ ID NO: 1922. In some embodiments, the heavy chain further comprises a signal peptide that is SEQ ID NO: 1923. In some embodiments, the heavy chain further comprises a signal peptide encoded by a nucleic acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 1926 or SEQ ID NO: 1927. In some embodiments, the heavy chain further comprises a signal peptide encoded by a nucleic acid sequence that is SEQ ID NO: 1926. In some embodiments, the heavy chain further comprises a signal peptide encoded by a nucleic acid sequence that is SEQ ID NO: 1927. In some embodiments, the anti-Gal3 antibody or binding fragment thereof light chain further comprises a signal peptide. In some embodiments, the light chain further comprises a signal peptide having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 1924 or SEQ ID NO: 1925. In some embodiments, the light chain further comprises a signal peptide that is SEQ ID NO: 1924. In some embodiments, the light chain further comprises a signal peptide that is SEQ ID NO: 1925. In some embodiments, the light chain further comprises a signal peptide encoded by a nucleic acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 1926 or SEQ IDNO: 1927. In some embodiments, the light chain further comprises a signal peptide encoded by a nucleic acid sequence that is SEQ ID NO: 1926. In some embodiments, the light chain further comprises a signal peptide encoded by a nucleic acid sequence that is SEQ ID NO: 1927.In some embodiments, any one or more of the constructs shown in any one or more of FIG. 1-16 can be used in any one or more of the embodiments provided herein (e.g., methods of treatment or uses in the preparation of a medicament for a therapy, etc.).

[0222] As applied to any of the methods of treatment 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.

[0223] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is administered intravenously. As applied to any of the methods of treatment disclosed herein, in some embodiments, the anti-Gal3 antibody or binding fragment thereof is formulated for systemic administration. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is formulated for intravenous administration. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is formulated for parenteral administration.

[0224] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is formulated for intravenous administration.

[0225] In some embodiments, more than one anti-Gal3 antibody or binding fragment is administered. In some embodiments, when more than one anti-Gal3 antibody or binding fragment is administered, the more than one anti-Gal3 antibodies or binding fragments thereof may be selected from the anti-Gal3 antibodies or binding fragments thereof disclosed herein. In some embodiments, any of the methods disclosed herein involving an anti-Gal3 antibody or binding fragment can be performed with an antigen binding molecule that binds to Gal3.

[0226] As applied to any of the methods disclosed herein, administering an anti-Gal3 antibody or binding fragment thereof to the subject comprises administration of one or more unit doses of the anti-Gal3 antibody or binding fragment thereof, optionally 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 unit doses. In some embodiments, 5, 6, 7, 8, 9, or 10 unit doses are administered. In some embodiments, 5 unit doses are administered. In some embodiments, 8 unit doses are administered. In some embodiments the unit doses are administered intravenously.

[0227] In some embodiments, the one or more unit doses comprise 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2500, 3000, 3500, 4000, 4500 or 5000 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose, or any amount per unit dose within a range defined by any two of the aforementioned amounts per unit dose. In some embodiments, the one or more unit doses are between 70 to 5000 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose. In some embodiments, the one or more unit doses comprise 800, 900, 1000, 1100, 1200, 1300, 1400, or 1500 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose, or any amount per unit dose within a range defined by any two of the aforementioned amounts per unit dose. In some embodiments, the one or more unit doses comprise 1000 mg or about 1000 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose. In some embodiments, the one or more unit doses comprise 4000 mg or about 4000 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose.

[0228] In some embodiments, the one or more unit doses comprise 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, or 150 mg / kg weight of the subject, or any amount per unit dose within a range defined by any two of the aforementioned amounts per unit dose. In some embodiments, the one or more unit doses comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 mg / kg weight of the subject, or any amount per unit dose within a range defined by any two of the aforementioned amounts per unit dose. In some embodiments, the one or more unit doses comprise 10 mg / kg or about 10 mg / kg weight of the subject. In some embodiments, a combined total of 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, or 10000 mg of anti- Gal3 antibody or binding fragment thereof is administered to the subject. In some embodiments, a combined total of 4000, 4500, 5000, 5500, or 6000 mg of anti-Gal3 antibody or binding fragment thereof is administered to the subject. In some embodiments, a combined total of 5000 mg of anti- Gal3 antibody or binding fragment thereof is administered to the subject. In some embodiments, a combined total of 4000 mg of anti-Gal3 antibody or binding fragment thereof is administered to the subject. In some embodiments the anti-Gal3 antibody or binding fragment thereof is administered every 2, 3 or 4 weeks. In some embodiments the anti-Gal3 antibody or binding fragment thereof is administered every 4 weeks. In some embodiments the anti-Gal3 antibody or binding fragment thereof is administered intravenously.

[0229] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is administered at 5mg / kg to 150mg / kg of antibody by weight of the subject. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is administered at 60 mg / kg of antibody by weight of the subject. In some embodiments, the anti-Gal3 antibody is administered at 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 57, 59, 60, 62, 65, 67, 70, 72, 75, 77, 80, 82, 85, 87, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, or 150 mg / kg weight of the subject, or any amount per unit dose within a range defined by any two of the aforementioned amounts.

[0230] In some embodiments, the anti-Gal3 antibody or binding fragment thereof is administered at least once per week. In some embodiments, the one or more unit doses are administered every 1, 2, 3, 4, 5, 6, or 7 days, or 1, 2, 3, or 4 weeks, or any interval within a range defined by any two of the aforementioned intervals. In some embodiments, the one or more unit doses are administered every 7 days or about 7 days. In some embodiments, the one or more unit doses are administered every 1, 2, 3 or 4 weeks. In some embodiments the one or more unit doses are administered every 2 weeks. In some embodiments the one or more unit doses are administered every 3 weeks. In some embodiments the one or more unit doses are administered every 4 weeks. In some embodiments the one or more unit doses are administered intravenously, for example every 2, 3 or 4 weeks. In some embodiments, the one or more unit doses comprise 1000 mg or about 1000 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose and the unit doses are administered every 7 days or about 7 days. In some embodiments, the one or more unit doses comprise 1000 mg or about 1000 mg of the anti-Gal3 antibody or binding fragment thereof and the unit doses are administered every 2, 3 or 4 weeks. In some embodiments, the one or more unit doses comprise 4000 mg or about 4000 mg of the anti-Gal3 antibody or binding fragment thereof and the unit doses are administered every 2, 3 or 4 weeks. In some embodiments, 5 unit doses comprising 1000 mg or about 1000 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose and the unit doses are administered every 7 days or about 7 days. In some embodiments, the one or more unit doses are administered over the course of 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 minutes, or any amount of time within a range defined by any two of the aforementioned durations. In some embodiments, the one or more unit doses are administered over the course of 60 minutes or about 60 minutes. In some embodiments the one or more unit doses are administered by IV.

[0231] As applied to any of the methods of use or treatment disclosed herein, the subject is a mammal. In some embodiments, the mammal is a human. In some embodiments, the subject is a mammal, such as a rodent (e.g. a guinea pig, a hamster, a rat, a mouse), murine (e.g. a mouse), canine (e.g. a dog), feline (e.g. a cat), equine (e.g. a horse), a primate, simian (e.g. a monkey or ape), a monkey (e.g. marmoset, baboon), an ape (e.g. gorilla, chimpanzee, orangutan, gibbon), pig, cow, sheep, goat or a human. Pharmaceutical Formulations

[0232] A pharmaceutical formulation for treating a neurodevelopmental disorder as provided herein can comprise an anti-Gal3 antibody or binding fragment thereof described herein. The anti-Gal3 antibody or binding fragment thereof can be formulated for systemic administration. Alternatively, the anti-Gal3 antibody or binding fragment thereof can be formulated for parenteral administration. In some embodiments, the anti-Gal3 antibody or binding fragment thereof is formulated for intravenous administration.

[0233] In some embodiments, an anti-Gal3 antibody or binding fragment thereof is formulated as a pharmaceutical composition for administration to a subject by, but not limited to, parenteral (e.g., intravenous, subcutaneous, intramuscular, intraarterial, intradermal, intraperitoneal, intravitreal, intracerebral, or intracerebroventricular), oral, intranasal, buccal, rectal, or transdermal administration routes. In some instances, the pharmaceutical composition described herein is formulated for parenteral (e.g., intravenous, subcutaneous, intramuscular, intraarterial, intradermal, intraperitoneal, intravitreal, intracerebral, or intracerebroventricular) administration. In other instances, the pharmaceutical composition described herein is formulated for systemic administration. In other instances, the pharmaceutical composition described herein is formulated for oral administration. In still other instances, the pharmaceutical composition described herein is formulated for intranasal administration. In some embodiments, the antibodies or binding fragments thereof disclosed herein are provided in a subcutaneous formulation or an intravenous formulation. In some embodiments, the antibodies or binding fragments thereof disclosed herein are provided in an intravenous formulation.

[0234] In some instances, the pharmaceutical compositions further include pH adjusting agents or buffering agents which include acids such as acetic, boric, citric, lactic, phosphoric and hydrochloric acids; bases such as sodium hydroxide, sodium phosphate, sodiumborate, sodium citrate, sodium acetate, sodium lactate and tris-hydroxymethylaminomethane; and buffers such as citrate / dextrose, sodium bicarbonate and ammonium chloride. Such acids, bases and buffers are included in an amount required to maintain pH of the composition in an acceptable range.

[0235] In some instances, the pharmaceutical compositions include one or more salts in an amount required to bring osmolality of the composition into an acceptable range. Such salts include those having sodium, potassium or ammonium cations and chloride, citrate, ascorbate, borate, phosphate, bicarbonate, sulfate, thiosulfate or bisulfite anions; suitable salts include sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfite and ammonium sulfate. In some embodiments, the pharmaceutical composition comprises sodium chloride.

[0236] In some instances, the pharmaceutical compositions further include diluent which are used to stabilize compounds because they can provide a more stable environment. Salts dissolved in buffered solutions (which also can provide pH control or maintenance) are utilized as diluents in the art, including, but not limited to a phosphate buffered saline solution. In certain instances, diluents increase bulk of the composition to facilitate compression or create sufficient bulk for homogenous blend for capsule filling. Such compounds can include e.g., lactose, starch, mannitol, sorbitol, dextrose, microcrystalline cellulose such as Avicel®; dibasic calcium phosphate, dicalcium phosphate dihydrate; tricalcium phosphate, calcium phosphate; anhydrous lactose, spray-dried lactose; pregelatinized starch, compressible sugar, such as Di-Pac® (Amstar); mannitol, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose acetate stearate, sucrose- based diluents, confectioner’s sugar; monobasic calcium sulfate monohydrate, calcium sulfate dihydrate; calcium lactate trihydrate, dextrates; hydrolyzed cereal solids, amylose; powdered cellulose, calcium carbonate; glycine, kaolin; mannitol, sodium chloride; inositol, bentonite, and the like.

[0237] In some embodiments, the pharmaceutical formulations include, but are not limited to, aqueous liquid dispersions, self-emulsifying dispersions, solid solutions, liposomal dispersions, aerosols, solid dosage forms, powders, immediate release formulations, controlled release formulations, fast melt formulations, tablets, capsules, pills, delayed release formulations, extended release formulations, pulsatile release formulations, multi-particulate formulations (e.g., nanoparticle formulations), and mixed immediate and controlled release formulations.

[0238] Provided herein in some embodiments are pharmaceutical formulations of any one or more of the anti-Gal3 antibodies or binding fragments disclosed herein. These pharmaceutical formulations may be in the form of prepared solutions that are compatible for administration, such as contained in a sterile IV infusion bag or other container. In some embodiments, the pharmaceutical formulation is prepared in an IV infusion bag.

[0239] In some embodiments, the pharmaceutical formulations are prepared as unit doses. In some embodiments, the pharmaceutical formulations are unit doses formulated as 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2500, 3000, 3500, 4000, 4500 or 5000 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose, or any amount per unit dose within a range defined by any two of the aforementioned amounts per unit dose. In some embodiments, the pharmaceutical formulations are unit doses formulated as 1000 mg or about 1000 mg of the anti-Gal3 antibody or binding fragment thereof. In some embodiments, the pharmaceutical formulations are unit doses formulated as 4000 mg or about 4000 mg of the anti-Gal3 antibody or binding fragment thereof. In some embodiments, the pharmaceutical formulations are unit doses (such as in the amounts provided herein) prepared in 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, or 300 mL of sterile saline or other compatible excipient, carrier, or diluent known in the art. In some embodiments, the pharmaceutical formulations are unit doses (such as in the amounts provided herein) prepared in 250 mL or about 250 mL of sterile saline or other compatible excipient, carrier, or diluent known in the art.

[0240] Also provided herein are pharmaceutical formulations comprising 1000 mg or about 1000 mg of an anti-Gal3 antibody or binding fragment thereof dissolved in 250 mL or about 250 mL of saline.

[0241] Also provided herein are pharmaceutical formulations comprising 1000 mg or about 1000 mg of an anti-Gal3 antibody diluted in 0.9% Sodium Chloride Injection, USP (normal sterile saline) in a volume of 250 mL or about 250 mL. In some embodiments, the anti-Gal3 antibody is TB006.

[0242] Also provided herein are pharmaceutical formulations comprising 4000 mg or about 4000 mg of an anti-Gal3 antibody or binding fragment thereof dissolved in 300 mL or about 300 mL of saline.

[0243] Also provided herein are pharmaceutical formulations comprising 4000 mg or about 4000 mg of an anti-Gal3 antibody or fragment thereof diluted in 0.9% Sodium Chloride Injection, USP (normal sterile saline) in a volume of 300 mL. In some embodiments, the anti-Gal3 antibody is TB006.

[0244] Also provided herein are single-use sealed injectable glass vials comprising a pharmaceutical formulation of any one or more of the anti-Gal3 antibodies or binding fragments thereof disclosed herein. In some embodiments, the vials comprise 4, 5, 6, 7, 8, 9, 10, 11, or 12 mL of a concentrated solution of the anti-Gal3 antibody or binding fragment thereof. In some embodiments, the vials comprise 8 mL of a concentrated solution of the anti-Gal3 antibody or binding fragment thereof. In some embodiments, the concentrated solution, which is meant to be diluted prior to administration, is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 mg / mL. In some embodiments, the concentrated solution, which is meant to be diluted prior to administration, is 20 mg / mL of the anti-Gal3 antibody or binding fragment thereof. In some embodiments, the pharmaceutical compositions disclosed herein for administration (e.g. those prepared in an IV infusion bag or other container) may be prepared by diluting the concentrated solution in the vials.

[0245] Also provided herein are single-use sealed injectable glass vials comprising 8 mL or about 8 mL of 20 mg / mL or about 20 mg / mL (i.e. total of 160 mg or about 160 mg) of an anti-Gal3 antibody or binding fragment thereof.

[0246] Also provided herein are pharmaceutical formulations comprising TB006 supplied in 8 mL glass vials, sealed with a rubber stopper and an aluminum flip top, with a strength of 160 mg (20 mg / mL, 8 mL) TB006 per vial. In some embodiments, the pharmaceutical formulation is stored at 2-8°C. In some embodiments, the pharmaceutical formulation is stored at, at about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10°C or any temperature within a range defined by any two of the aforementioned temperatures. Diagnostic Antibodies and Methods of Diagnosis

[0247] In some embodiments, anti-Gal3 diagnostic antibodies for diagnosis of ASD and / or ADHD are disclosed. In some embodiments, a diagnostic antibody for diagnosis of ASD and / or ADHD comprises an anti-Gal3 antibody comprising a detectable moiety. In some embodiments, the detectable moiety comprises radioactive material.

[0248] In some embodiments, an anti-Gal3 antibody is conjugated to a radioactive substance for use in detecting and / or diagnosing a subject as having, or at risk of having, a ASD and / or ADHD. In some embodiments, the radioactive substance comprise, but are not limited to,18F,18F-FAC,32P,33P,45Ti,47Sc,52Fe,59Fe,62Cu,64Cu,67Cu,67Ga,68Ga,75Sc,77As,86Y,90Y,89Sr,89Zr,94Tc,94Tc,99mTc,99Mo,105Pd,105Rh,111Ag,111In,123I,124I,125I,131I,142Pr,143Pr,149Pm,153Sm,154-of having, ASD and / or ADHD. In some embodiments, the anti-Gal3 antibody conjugated to18F,18F- FAC,32P,33P,45Ti,47Sc,52Fe,59Fe,62Cu,64Cu,67Cu,67Ga,68Ga,75Sc,77As,86Y,90Y,89Sr,89Zr,94Tc,94Tc,99mTc,99Mo,105Pd,105Rh,111Ag,111In,123I,124I,125I,131I,142Pr,143Pr,149Pm,153Sm,154-diagnose a subject as having, or being at risk of having, ADHD and / or ASD.

[0249] In some embodiments, the methods disclosed herein further comprise detecting Gal3 by detecting antibody binding to Gal3, for example by visualizing a detectable marker conjugated to anti-Gal3 antibody or a binding fragment thereof in the subject. In some embodiments, Gal3 is detected in the brain, heart, lungs, kidney, bones, plasma, other body systems, and / or any combination thereof. In some embodiments, the detectable marker comprises a radioactive substance. In some embodiments, the radioactive substance is detected in the subject’s brain, heart, lungs, kidney, bones, plasma, blood, and other body systems. In some embodiments, the radioactive substance is detected using one or more imaging devices. For example, in some embodiments, the detectable marker comprises a radioactive substance that is detected by gamma camera, SPECT, PET, MRI, CT, or any combination thereof. It is contemplated that any suitable imaging or detection method would be suitable for use with the methods disclosed herein. In some embodiments, the anti-Gal3 antibody conjugated to a detectable marker is used as a primary means of diagnosis or risk assessment for ASD and / or ADHD. In some embodiments, the anti-Gal3 antibody conjugated to a detectable marker is used as a supplement to one or more additional methods of diagnosis and / or risk assessment for ASD and / or ADHD.

[0250] In some embodiments, diagnosing a subject as having ADHD and / or ASD comprises an assessment of Gal3 detection in the subject with, at risk of, or suspected of having,ASD and / or ADHD relative to a reference amount in a healthy subject. In some embodiments, Gal3 detection comprises administering an anti-Gal3 antibody that is conjugated to a detectable moiety to a subject having, at risk of, or suspected of having ASD and / or ADHD. The detectable moiety is detected in the subject to determine the level of Gal3 in the subject. In some embodiments an anti-Gal3 antibody or binding fragment thereof may also be administered to a healthy subject in order to determine a baseline level of Gal3. In some embodiments, the detectable moiety comprises a radioactive substance. In some embodiments, the diagnosis of ASD and / or ADHD comprises an assessment of Gal3 levels in a subject having, at risk of having, or suspected of having or being at risk of having, ASD and / or ADHD relative to a reference amount in a healthy subject. In some embodiments, detectable Gal3 levels in a subject having or at risk of ASD and / or ADHD is indicated by a subject having about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, 100, 125, 150, 175, 200, 250, 300, 400, 500, 600, 750, 800, 900, or 1000%, more detectable Gal3 than a healthy subject, or having a detectable Gal3 level that is in a range defined by any two of the preceding values. For example, in some embodiments, detectable Gal3 levels in a subject having or at risk of having ASD and / or ADHD is indicated by a subject having between about 1-1000, 1-750, 1-500, 1-250, 1-100, 1-75, 1-50, 1-25, 1-10, -15, 5-1000, 5-750, 5-500, 5- 250, 5-100, 5-75, 5-50, 5-25, 5-10, 10-1000, 10-750, 10-500, 10-250, 10-100, 10-75, 10-50, 10- 25, 25-1000, 25-750, 25-500, 25-250, 25-100, 25-75, 25-50, 50-1000, 50-750, 50-500, 50-250, 50- 100, 100-1000, 100-750, 100-500, 100-250, 250-1000, 250-750, 250-500, 500-1000, 500-750, or 750-1000%, more detectable Gal3 than a healthy subject. Kit / Article of Manufacture

[0251] Disclosed herein, in certain embodiments, are kits and articles of manufacture for use with one or more of the methods described herein. Such kits include a carrier, package, or container that is compartmentalized to receive one or more containers such as vials, tubes, and the like, each of the container(s) comprising one of the separate elements to be used in a method described herein. Suitable containers include, for example, bottles, vials, syringes, and test tubes. In one embodiment, the containers are formed from a variety of materials such as glass or plastic.

[0252] The articles of manufacture provided herein contain packaging materials. Examples of pharmaceutical packaging materials include, but are not limited to, blister packs,bottles, tubes, bags, containers, bottles, and any packaging material suitable for a selected formulation and intended mode of administration and treatment.

[0253] For example, the container(s) include an anti-Gal3 antibody as disclosed herein, host cells for producing one or more antibodies described herein, and / or vectors comprising nucleic acid molecules that encode the antibodies described herein. Such kits optionally include an identifying description or label or instructions relating to its use in the methods described herein.

[0254] A kit typically includes labels listing contents and / or instructions for use, and package inserts with instructions for use. A set of instructions will also typically be included.

[0255] In one embodiment, a label is on or associated with the container. In one embodiment, a label is on a container when letters, numbers or other characters forming the label are attached, molded or etched into the container itself; a label is associated with a container when it is present within a receptacle or carrier that also holds the container, e.g., as a package insert. In one embodiment, a label is used to indicate that the contents are to be used for a specific therapeutic application. The label also indicates directions for use of the contents, such as in the methods described herein.

[0256] In certain embodiments, the pharmaceutical compositions used in methods herein are presented in a pack or dispenser device which contains one or more unit dosage forms containing a compound provided herein. The pack, for example, contains metal or plastic foil, such as a blister pack. In one embodiment, the pack or dispenser device is accompanied by instructions for administration. In one embodiment, the pack or dispenser is also accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration. Such notice, for example, is the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product insert. In one embodiment, compositions containing a compound provided herein formulated in a compatible pharmaceutical carrier are also prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.Examples Example 1 – Expression of Gal-3 in microglia in the pathologic brain.

[0257] The expression of Gal-3 in the brains with neurological disorders was assessed. For the assessment, APPSwe transgenic mice were used as a model of Alzheimer’s Disease and permanent occlusion of the middle cerebral artery (pMCAO) mice were used as a model of ischemic stroke.

[0258] FIG.17 is an illustrative representation of expression of Gal-3 in microglia brain using immunofluorescence staining of mouse brain sections in AD and stroke model. Iba-1 was used as a microglia marker. As illustrated in FIG. 17, Gal-3 was found colocalized with microglia, as indicated by Iba-1, in both APPSwe mice and ischemic stroke mice. DAPI was used to stain the nucleus. Example 2 – The effect of anti-Gal3 antibodies on microglial activation

[0259] The anti-neuroinflammatory effect of anti-Gal3 antibodies was evaluated using, APPSwe mice and pMCAO mice.

[0260] Mice were intraperitoneally injected biweekly with 10 mg / kg TB001, the mouse analog of TB006. MOPC or MOPC21 were administered as nonspecific isotype control antibodies. Immunochemistry (IHC) was employed to measure microglial population, with Iba-1 as the marker of microglial activation.

[0261] FIGS. 18A-18D are illustrations depicting an embodiment of inhibition of microglial activation by anti-Gal3 antibodies. As is clear from FIG. 18A, TB001 treatment significantly reduced microglial area in the hippocampus of APPSwe mice. FIG. 18B is a bar graph showing quantification of microglia in WT mice, MOPC21 and TB001 treated mice. Further, as illustrated in FIG. 18C, TB001 treatment significantly reduced microglial area in the striatum and thalamus of pMCAO-induced ischemic stroke mice. FIG.18D is a bar graph showing quantification of microglia in WT mice, MOPC and TB001 treated mice. Example 3 – Efficacy and tolerability of TB006 treatment for improving symptoms in adults with Autism Spectrum Disorder (ASD)

[0262] The efficacy and tolerability of anti-Gal3 antibody TB006 will be examined in adults with ASD. For this examination, three sites at different autism centers will be selected. Allthree sites will conduct a two-year study of a 14-week randomized, double-blind placebo- controlled (DBPC) trial followed by a 14-week open label extension using TB006 in at least 45 adults with ASD. During the study, adults with ASD will be evaluated for change in ASD symptoms as determined by the Childhood Autism Rating Scale-2 (CARS) and Ohio Autism Clinical Impressions Scale (OACIS) during the Parent Examiner Social Interaction (PESI) test, the change in neurobehavioral function on the NIH Toolbox (nihtoolbox.org), the tolerability of TB006 in adults with ASD, the overall change in core ASD symptoms of social communication (ABC-Social Withdrawal subscale, SRS-Social Communication Index Summary Scale, VABS Social Subscale) and change in repetitive behavior (ABC-Stereotypies, SRS-Repetitive Behavior Index).

[0263] The primary study endpoint will be the change in ASD symptoms as determined by Childhood Autism Rating Scale-2 (CARS). The secondary study endpoints will comprise evaluating changes in ASD symptoms as determined by the OACIS rating of the PESI, changes in neurobehavioral function on the NIH Toolbox, changes in core ASD symptoms of social communication (ABC-Social Withdrawal, SRS-Social Communication Index, VABS Social Subscale) and changes in repetitive behavior (ABC-Stereotypies, SRS-Repetitive Behavior Index). A safety analysis will also be performed to compare AEs between treatment groups. Subject Selection and Withdrawal

[0264] The study will include adults with ASD without exclusion due to race or ethnicity. Both genders will be studied. The inclusion and exclusion criteria for adults with ASD enrolled in the study are listed below. Inclusion Criteria

[0265] Autism Spectrum Disorder as defined below by the ADOS or ADI-R.

[0266] Between 18 and 35 years of age at baseline.

[0267] English is included in the languages in which the individual is being raised.

[0268] Autism severity of moderate or higher (≥4) under the 7-item clinical global impression-severity scale

[0269] Ability to maintain all ongoing complementary, dietary, traditional, and behavioral treatments constant for the study period.

[0270] Unchanged complementary, dietary, traditional, and behavioral treatments for two months prior to study entry.

[0271] In males and females of childbearing age, two forms of birth control must be used unless they are not sexually active. Exclusion Criteria

[0272] LGALS3 rs4644 single nucleotide polymorphism with two copies of the Variant-type allele.

[0273] History of infusion reactions with immunoglobulin product.

[0274] Significant self-abusive or violent behavior or evidence of suicidal ideation, plan or behavior.

[0275] Severely affected as defined by CGI-Severity Standard Score = 7 (Extremely Ill).

[0276] Severe prematurity (<34 weeks gestation) as determined by medical history.

[0277] Current uncontrolled gastroesophageal disorders.

[0278] Current or history of liver or kidney disease as determined by medical history and safety labs.

[0279] Genetic syndromes.

[0280] Congenital brain malformations.

[0281] Active Epilepsy Diagnosis

[0282] Any medical condition that the PI determines could jeopardize the safety of the study subject or compromise the integrity of the data.

[0283] Significant negative reaction (i.e. fainting, vomiting, etc.) because of a previous blood draw.

[0284] Failure to thrive or < 5%ile for Body Mass Index or weight at the time of screening.

[0285] Concurrent treatment with drug that would significantly interact with the investigational product.

[0286] Allergy or Sensitivity to ingredients in the investigational product or placebo.

[0287] Evaluation with the NIH Toolbox or BOSCC within 3 months of entering the study.

[0288] Planned evaluation with the NIH Toolbox or BOSCC during the study.

[0289] Pregnancy.

[0290] The participant intends to initiate, discontinue, or modify the regular dosage of substances that could potentially influence their behavior. These include, but are not limited to, mild psychotropic agents such as diphenhydramine and coffee.

[0291] Positive urine result for illegal substances (including cannabis) at Screening. History of alcohol abuse within the last five years. Treatment Regimen

[0292] For this study, all subjects will receive TB006 or placebo at a dose of 4000 mg via a 1- to 2-hour continuous Intravenous (IV) infusion every 3 weeks. A total of five doses will be given to all the subjects. Upon double-blind study completion, TB006 will be given in an Open- label extension study for the placebo subjects.

[0293] TB006 sterilized drug product is supplied in 8 mL glass vials, sealed with a rubber stopper and an aluminum flip top, with strength of 160 mg (20 mg / mL, 8 mL) TB006 drug product per vial. TB006 drug product can be stored at 2-8°C (36-46°F). The opened vials should be used immediately for the preparation. The dose formulation should be a sterile, white, off-white, or light-yellow solution.

[0294] Local regulations, institutional guidelines, and site policy for safe TB006 monoclonal antibody handling will be followed. Recommended safety measures for the handling and preparation of TB006 include personal protective equipment (PPE; including sterile gloves, protective eyewear, and lab coat or gown), and vertical laminar airflow safety cabinets. Laminar Flow Hood can be used with TB006 and is acceptable based on local regulations, institutional guidelines, and site policies.

[0295] TB006 drug product will be administered via IV infusion over 60-120 minutes, after adding the proper volume (200 mL) to an IV bag containing 300 mL of 0.9% Sodium Chloride Injection, USP (normal saline) for a total of 500 mL. The infusion rate will be slowed or stopped if any adverse events arise based on the judgment of the PI. The investigator or designee must confirm appropriate temperature conditions have been maintained during transit for all study intervention received, and any discrepancies are reported and resolved before use of the study intervention.

[0296] TB006 will be administered using an IV infusion bag or syringe composed of compatible materials. The entire contents of the IV bag will be administered over 60-120 minutes. The rate of infusion should be per institutional standard, but should not exceed 500 mL / hr. TB006 cannot be mixed with other medications. A 0.2 micron in-line filter will be used during the IV administration. After completion of the TB006 infusion, the line will be flushed per institutional standard with an adequate flush volume to ensure administration of the full dose. Post infusion, all reactions or complications encountered during the administration of TB006 will be documented. Waste disposal responsibility will be managed according to the site / institutional SOP on disposal of hazardous waste. After dosing the participant, needle and IV bag will be discarded properly according to site / institution’s SOPs on disposal of hazardous waste and the investigational product accountability log with dose amount and route of administration will be completed. Study Procedures

[0297] Baseline assessments will occur within 28 days of screening to provide a review of screening laboratory results. At baseline, an examiner will conduct the Childhood Autism Rating Scale-2 (CARS), the PESI test and remaining assessments will be completed, including the NIH Toolbox, Social Responsiveness Scale (SRS), Vineland Adaptive Behavior Scale (VABS) (with a designated trained interviewer), and Major Parental Concerns (MPC). The OACIS will be scored from the PESI test.

[0298] Select measures will also be performed at 6 weeks, including the ABC, SRS, CGI, CARS. The schedule of procedures is provided in Table 1 below. Table 1 Table. Schedule of Procedures Double-Blind Phase (weeks) Open Label (wks) MeasureS 0 1 3 4 6 7 9 10 12 14 1† 3 6 9 12 14CGI-Improvement X X X OACIS-Severity X X OACIS-Improvement X X X X X X X X X X X ts ge veExample 4 – Efficacy and tolerability of TB006 treatment for improving symptoms in subjects with Attention-Deficit Hyperactivity Disorder (ADHD)

[0299] The efficacy and tolerability of anti-Gal3 antibody TB006 will be examined in adults with ADHD. During the study, subjects with ADHD will be evaluated for change in ADHD symptoms as determined by Conners Rating Scales, Vanderbilt ADHD Rating Scales, Tests of Variable Attention (TOVA), ADHD Rating Scale-IV (ADHD-RS-IV), Adult ADHD Self-Report Scale (ASRS), Adult ADHD Self-Report Scale (ASRS) Screener, Brown Attention-Deficit Disorder Symptom Assessment Scale (BADDS) for Adults, ADHD Rating Scale IV (ADHD-RS- IV) With Adult Prompts or other methods of assessing ADHD known by a person skilled in the art.

[0300] The primary study endpoint will be the change in ADHD symptoms as determined by Conners Rating Scales, Vanderbilt ADHD Rating Scales, ADHD Rating Scale-IV (ADHD-RS-IV), Tests of Variable Attention (TOVA), Adult ADHD Self-Report Scale (ASRS), Adult ADHD Self-Report Scale (ASRS) Screener, Brown Attention-Deficit Disorder Symptom Assessment Scale (BADDS) for Adults, ADHD Rating Scale IV (ADHD-RS-IV) With AdultPrompts. A safety analysis will also be performed to compare AEs between treatment groups or other methods of assessing ADHD known by a person skilled in the art.

Claims

WHAT IS CLAIMED IS:

1. A method of treating or reducing the development of an autism spectrum disorder (ASD) or associated symptoms thereof in a subject in need thereof, the method comprising: identifying a subject as having or being at risk of having ASD or associated symptoms thereof, and administering an anti-Gal3 antibody or a binding fragment thereof to the subject, wherein administration of the anti-Gal3 antibody treats and / or reduces the development of ASD or associated symptoms thereof in the subject.

2. A method of reducing and / or inhibiting the activity of Galectin-3 (Gal3) in a subject with an autism spectrum disorder (ASD) or associated symptoms thereof, the method comprising: identifying a subject as having or being at risk of having ASD or associated symptoms thereof, and administering an anti-Gal3 antibody or a binding fragment thereof to the subject, wherein administration of the anti-Gal3 antibody reduces and / or inhibits the activity of Gal3 in the subject as compared to the activity of Gal3 in the subject prior to administration of the anti-Gal3 antibody.

3. The method of claim 1 or 2, wherein the associated symptoms comprise at least one of impaired social communication, impaired cognitive skills, impaired social cognitive skills, impaired motor function, impaired attention, or emotional abnormalities.

4. A method of treating or reducing the development of an attention deficit hyperactivity disorder (ADHD) or associated symptoms thereof in a subject in need thereof, the method comprising: identifying a subject as having or being at risk of having ADHD or associated symptoms thereof, and administering an anti-Gal3 antibody or a binding fragment thereof to the subject, whereinadministration of the anti-Gal3 antibody treats and / or reduces the development of ADHD or associated symptoms thereof in the subject.

5. A method of reducing and / or inhibiting the activity of Galectin-3 (Gal3) in a subject with an attention deficit hyperactivity disorder (ADHD) or associated symptoms thereof, the method comprising: identifying a subject as having or being at risk of having ADHD or associated symptoms thereof, and administering an anti-Gal3 antibody or a binding fragment thereof to the subject, wherein administration of the anti-Gal3 antibody reduces and / or inhibits the activity of Gal3 in the subject as compared to the level of Gal3 in the subject prior to administration of the anti-Gal3 antibody.

6. The method of claim 4 or 5, wherein the associated symptoms comprise impaired cognitive functions, impaired psychosocial functions or impaired behavioral functions.

7. The method of any one of claims 1-6, wherein administering the anti-Gal3 antibody or a binding fragment thereof to the subject comprises administration of one or more-unit doses of the anti-Gal3 antibody or a binding fragment thereof, optionally 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 unit doses.

8. The method of claim 7, wherein the one or more unit doses comprise 10, 20, 20, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2500, 3000, 3500, 4000, 4500 or 5000 mg of the anti-Gal3 antibody or binding fragment thereof per unit dose, or any amount per unit dose within a range defined by any two of the aforementioned amounts per unit dose.

9. The method of claim 7 or 8, wherein the one or more unit doses comprise 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, or 150 mg / kg weight of the subject, or any amount per unit dose within a range defined by any two of the aforementioned amounts per unit dose.

10. The method of any one of claims 7-9, wherein the one or more-unit doses are administered every 1, 2, 3, 4, 5, 6, or 7 days, or 1, 2, 3, or 4 weeks, or any interval within a range defined by any two of the aforementioned intervals.

11. The method of any one of the preceding claims, wherein the anti-Gal3 antibody or binding fragment thereof comprises TB006.

12. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 31; the VH-CDR2 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 72; the VH-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 113; the VH-CDR1 comprises an amino acid sequence having at least 90%identity to SEQ ID NO: 171; the VH-CDR1 comprises an amino acid sequence having at least 90%identity to SEQ ID NO: 222; and the VH-CDR1 comprises an amino acid sequence having at least 90%, to SEQ ID NO:

249.

13. The method of any one of claims 1-11, wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3, and a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3; wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 1940 or 1764, the VH-CDR2 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 77 or 1781, the VH-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 118 or 1798, the VL-CDR1 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 178 or 1815, the VL-CDR2 comprises anamino acid sequence having at least 90% identity to SEQ ID NOs: 229 or 1831, and the VL-CDR3 comprises an amino acid sequence having at least 90% identity to SEQ ID NOs: 256 or 1849.

14. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 1 VL-CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs:170-296 or 1814-1864.

15. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VL-CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs:170-296 or 1814-1864.

16. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 1 VH-CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-169, 801, 802, 951-954, 1763-1813 or 1940.

17. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VH-CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-169, 801, 802, 951-954, 1763-1813 or 1940.

18. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises at least 1 CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-296, 801, 802, 951-954, 1763-1813 or 1940.

19. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises at least 6 CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-296, 801, 802, 951-954, 1763-1813 or 1940.

20. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the VH-CDR1 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 27-70, 1763-1779 or 1940; the VH-CDR2 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 71-111, 801, 951, 952 or 1780-1796; the VH-CDR3 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NO: 112-169, 802, 953, 954 or 1797-1813; the VL-CDR1 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 170-220 or 1814-1830; the VL-CDR2 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 221-247 or 1831-1847; and the VL-CDR3 comprises an amino acid sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 248-296 or 1848-1864.

21. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a combination of the VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 as illustrated in FIG.

7.

22. The method of any one of claims 1-11, wherein the antibody comprises at least 1 CDR having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 170- 220, 221-247, 248-296, 27-70, 71-111, 801, 951-952,112-169, 802, 953-954, 1763-1864 or 1940.

23. The method of any one of claims 1-11, wherein the antibody comprises at least 6 CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 170- 220, 221-247, 248-296, 27-70, 71-111, 801, 951-952,112-169, 802 , 953-954,1763-1864 or 1940.

24. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain variable region comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 297-373, 803, 806-820, 940, 955-968, 1067- 1109, 1415-1439 or 1882-1898.

25. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a light chain, wherein the light chain variable region comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 374-447, 821-835, 941-943, 969-982, 1110- 1152, 1440-1464, 1899-1914 or 1921.

26. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 448-494, 804, 836-850, 983-996, 1153-1195, 1411, 1465- 1489 or 1679-1694.

27. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a light chain, wherein the light chain comprises a sequence having at least 90% identity to the sequence selected from SEQ ID NOs: 495-538, 805, 851-865, 997-1010, 1196-1238, 1412, 1490- 1514 or 1713-1728.

28. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VH-CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 31, 72, 113, 1940, 77, 118, 1764, 1781 or 1798.

29. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises (1) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3; and (2) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3, wherein the antibody comprises at least 3 VH-CDRs having at least 90% identity to any one of the amino acid sequences of SEQ ID NOs: 171, 222, 249, 178, 229, 256, 1815, 1831 or 1849.

30. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a heavy chain variable region, wherein the heavy chain variable region comprises a sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NO: 298, 1067, 814, 1928, 1920 or 1930.

31. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a light chain variable region, wherein the light chain variable region comprises a sequence having at least 90% identity to any one of the amino acid sequences of SEQ ID NO: 375, 1110, 829, 1931, 1932 or 1933.

32. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the SEQ ID NO: 449, 1153, 844, 1934, 1695 or 1935.

33. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a light chain, wherein the light chain comprises a sequence having at least 90% identity to SEQ ID NO: 496, 1196, 859, 1936, 1746 or 1937.

34. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a heavy chain variable region, wherein the heavy chain variable region comprises a sequence having at least 90% identity to SEQ ID NO:

309.

35. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a light chain variable region, wherein the light chain variable region comprises a sequence having at least 90% identity to SEQ ID NO: 387.

36. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a heavy chain, wherein the heavy chain comprises a sequence having at least 90% identity to the SEQ ID NO:

462.

37. The method of any one of claims 1-11, wherein the anti-Gal3 antibody comprises a light chain, wherein the light chain comprises a sequence having at least 90% identity to SEQ ID NO:

508.

38. The method of any one of the preceding claims, wherein the anti-Gal3 antibody 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, mIMT001, 4A11.2B5, 4A11.H1L1, 4A11.H4L2, 4G2.2G6, 6B3.2D3, 6H6.2D6, 9H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, 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, 846T.1H2, 847.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 847.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2- mH0mL2, 847.12C4, 847.4D3, 2D10-VH0-VL0, 2D10-hVH4-HVL1, 2D10-hVH4-HVL2, 2D10- hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 20H5.A3-VH3VL1, 20H5.A3-VH3VL3, 20H5.A3-VH4VL1, 20H5.A3- VH5VL1, 20H5.A3-VH5VL3, 20H5.A3-VH6VL1, 20H5.A3-VH6VL3, 2D10-VH0-VL0, 2D10- hVH4-HVL1, 2D10-hVH4-HVL2, 2D10-hVH4-HVL3, 2D10-hVH4-HVL4, 2D10-hVH3-HVL1, 2D10-hVH3-HVL2, 2D10-hVH3-HVL3, 2D10-hVH3-HVL4, 21H6-H0L0, 21H6-H1L1, 21H6- H1L2, 21H6-H1L3, 21H6-H1L4, 21H6-H2L1, 21H6-H2L2, 21H6-H2L3, 21H6-H2L4, 21H6- H3L1, 21H6-H3L2, 21H6-H3L3, 21H6-H3L4, 21H6-H4L1, 21H6-H4L2, 21H6-H4L3, 21H6- H4L4, 21H6-H5L1, 21H6-H5L2, 21H6-H5L3, 21H6-H5L4, 21H6-H6L1, 21H6-H6L2, 21H6- H6L3, 21H6-H6L4, or binding fragment thereof.

39. The method of any one of the preceding claims, wherein the anti-Gal3 antibody is administered at 5mg / kg to 150mg / kg weight of the subject.

40. The method of any one of the preceding claims, wherein the anti-Gal3 antibody is administered once every 2, 3 or 4 weeks.

41. The method of any of the preceding claims, wherein the subject is a human.

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