A method for treating inflammatory diseases by blocking galectin-3

Abstract

Disclosed herein are methods, antibodies, and compositions for interfering with the interaction between galectin-3 (Gal3) and viral proteins, such as proteins of the SARS-CoV-2 virus or other coronaviruses, or virus-associated host proteins. Further disclosed herein are methods, medicaments, and compositions for treating a disease or disorder in a subject, such as treating a viral infection or treating fibrosis that develops as a sequela of a viral infection, such as pulmonary fibrosis or cytokine release syndrome. Also disclosed herein are methods, medicaments, and compositions for treating an inflammatory disease or disorder in a subject, such as pulmonary inflammation or systemic lupus erythematosus, which may be associated with neutrophil activity. Also disclosed herein are pharmaceutical antibody formulations for treating diseases, such as coronavirus infections.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 030,069, filed on 26 May 2020, which is incorporated herein by express reference in its entirety.

[0002] Sequence listing reference This application is filed together with an electronically formatted sequence listing. The sequence listing is provided as a file named SeqListingIMMUT020WO.TXT, with a size of 783,884 bytes, created and last updated on May 25, 2021. The information in the electronic sequence listing is incorporated herein in its entirety by reference.

[0003] Field of Invention Aspects of this disclosure generally relate to antibodies or their conjugate fragments that bind to galectin-3 (Gal3). Some aspects bind to Gal3 and block its interaction with viral proteins, such as those of the SARS-CoV-2 virus or other coronaviruses, or with virus-associated host proteins. Aspects of this disclosure generally relate to antibodies or their conjugate fragments that reduce inflammation, for example, by reducing the activation of immune cells by Gal3. [Background technology]

[0004] Galectin-3 (Gal3, GAL3) is a lectin, or carbohydrate-binding protein, that has specificity for beta-galactosides. In human cells, Gal3 can be expressed and found in the nucleus, cytoplasm, cell surface, and extracellular space. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] International Publication No. 2019 / 023247 [Patent Document 2] International Publication No. 2020 / 160156 [Patent Document 3] U.S. Patent No. 5,985,660 [Patent Document 4] European Patent No. 404,097 [Patent Document 5] International Publication No. 93 / 11161 [Patent Document 6] International Publication No. 00 / 24782 [Patent Document 7] U.S. Patent Application Publication No. 2003 / 0133939 [Patent Document 8] U.S. Patent No. 5,969,108 [Patent Document 9] U.S. Patent No. 6,162,963 [Patent Document 10] U.S. Patent No. 6,150,584 [Patent Document 11] U.S. Patent No. 6,174,708 [Patent Document 12] U.S. Patent No. 5,624,659 [Patent Document 13] U.S. Patent No. 6,187,287 [Patent Document 14] European Patent No. 0,329,400 [Patent Document 15] U.S. Patent No. 5,270,202 [Patent Document 16] European Patent No. 699,755 [Patent Document 17] U.S. Patent No. 5,208,020 [Patent Document 18] U.S. Patent No. 5,416,064 [Patent Document 19] U.S. Patent No. 7,276,497 [Patent Document 20] U.S. Patent No. 6,716,821 [Patent Document 21] U.S. Patent Application Publication No. 2013 / 029900 Specification [Patent Document 22] U.S. Patent Application Publication No. 2013 / 0323268 [Patent Document 23] U.S. Patent No. 6,884,869 [Patent Document 24] U.S. Patent No. 7,659,241 [Patent Document 25] U.S. Patent No. 7,498,298 [Patent Document 26] U.S. Patent No. 7,964,566 [Patent Document 27] U.S. Patent No. 7,750,116 [Patent Document 28] U.S. Patent No. 8,288,352 [Patent Document 29] U.S. Patent No. 8,703,714 [Patent Document 30] U.S. Patent No. 8,871,720 [Patent Document 31] U.S. Patent No. 8,404,678 [Patent Document 32] U.S. Patent No. 8,163,736 [Patent Document 33] U.S. Patent No. 8,426,402 [Patent Document 34] U.S. Patent No. 8,802,667 [Patent Document 35] U.S. Patent No. 8,809,320 [Patent Document 36] U.S. Patent No. 6,562,806 [Patent Document 37] U.S. Patent No. 6,608,192 [Patent Document 38] U.S. Patent No. 7,704,924 [Patent Document 39] U.S. Patent No. 7,067,511 [Patent Document 40] U.S. Patent No. 7,612,062 [Patent Document 41] U.S. Patent No. 7,244,724 [Patent Document 42] U.S. Patent No. 7,528,126 [Patent Document 43] U.S. Patent No. 7,049,311 [Patent Document 44] U.S. Patent No. 8,633,185 [Patent Document 45] U.S. Patent No. 8,501,934 [Patent Document 46] U.S. Patent No. 8,697,688 [Patent Document 47] U.S. Patent Application Publication No. 2014 / 0294868 [Patent Document 48] U.S. Patent No. 9,242,013 [Patent Document 49] U.S. Patent Application Publication No. 2014 / 0286970 [Patent Document 50] U.S. Patent No. 8,936,910 [Patent Document 51] International Publication No. 2014 / 140317 [Patent Document 52] U.S. Patent Application Publication No. 2015 / 0105539 [Patent Document 53] U.S. Patent Application Publication No. 2015 / 0105540 [Patent Document 54] U.S. Patent No. 9,089,614 [Patent Document 55] International Publication No. 2015 / 038,426 [Patent Document 56] U.S. Patent No. 6,821,783 [Patent Document 57] U.S. Patent No. 5,695,937 [Patent Document 58] U.S. Patent No. 5,405,783

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Non-licensed literature

[0006] [Non-licensed document 1] Fehr AR & Perlman S. “Coronaviruses: An Overview of Their Replication and Pathogenesis” Methods Mol. Biol. (2015); 1282:1-23 [Non-licensed document 2] Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991 [Non-licensed document 3] Chothia and Lesk, J Mol Biol 196(4): 901-917, 1987

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[0007] Galectin-3 (Gal3) has been implicitly shown to possess immunomodulatory activity. An example of this is Gal3 and T-cell immunoglobulin and mucin-domain-containing Gal3 (T-cell immunoglobulin-3). This is an interaction between immunoglobulin and mucin-domain containing-3 (TIM-3), which can cause suppression of the immune response, such as T cell activation, allowing cancer cells to evade immune clearance. This phenomenon and methods for inhibiting it are illustrated in Patent Documents 1 and 2 (each of which is incorporated herein by express reference in whole).

[0008] The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, has had a tremendous impact on human mortality, the global economy, and the burden on public health infrastructure worldwide. Much remains unknown about how the virus interacts with the host immune system. However, uncontrolled inflammation in response to the SARS-CoV-2 coronavirus can significantly contribute to the increased risk of long-term complications and death. In addition, coronavirus immunotherapies or vaccines for humans are only just beginning to be approved. Therefore, there is a persistent need for new and effective treatments and preventive measures for inflammatory diseases in general, beyond just SARS-CoV-2 and other coronaviruses.

[0009] Disclosed herein are galectin-3 (Gal3) and viral proteins, such as proteins of the SARS-CoV-2 virus or other coronaviruses, such as Methods, antibodies, and compositions for interfering with the interaction between the coronavirus spike protein or a virus-associated host protein, including ACE2 or CD147.

[0010] Also disclosed herein are methods for treating viral infections, which may be associated with inflammatory symptoms. In some embodiments, the methods are directed to prevent and / or reduce viral spread, or to reduce the risk that a virus can enter a cell (e.g., either in vitro or in vivo).

[0011] Disclosed herein are methods, pharmaceuticals, and compositions comprising anti-Gal3 antibodies or their conjugated fragments for the treatment of diseases or disorders in a subject, such as viral infections, or fibrosis, such as pulmonary fibrosis which may develop as a sequela of a viral infection, or inflammatory diseases, such as chronic obstructive pulmonary disease (COPD).

[0012] Also disclosed herein are methods for treating cytokine release syndrome (CRS, cytokine storm) or sepsis caused, for example, by bacterial, viral, fungal, or protozoan infections, and the use of anti-Gal3 antibodies or their conjugated fragments. In some embodiments, CRS may be a result of sepsis. In some embodiments, CRS is a result of coronavirus infection, for example, SARS-CoV-2 infection.

[0013] Also disclosed herein are methods, pharmaceuticals, and compositions comprising anti-Gal3 antibodies or their conjugated fragments for the treatment of inflammatory diseases or for reducing or inhibiting inflammation in a subject. In some embodiments, this inflammation may be associated with the activation and / or migration of immune cells, such as neutrophils. In some embodiments, administration of an anti-Gal3 antibody or its conjugated fragment reduces or inhibits neutrophil activation and / or migration in a subject. In some embodiments, administration of an anti-Gal3 antibody or its conjugated fragment reduces or inhibits the cleavage of CD62L expressed by neutrophils and / or reduces or inhibits IL-8 production in a subject. In some embodiments, administration of an anti-Gal3 antibody or its conjugated fragment reduces the number of neutrophils in a subject. In some embodiments, administration of an anti-Gal3 antibody or its conjugate modulates the expression of Gal3, myeloperoxidase (MPO), growth-related oncogene α (GROα) / keratinocyte-derived chemokine (KC), Ly6c1, INOS, IL-6, TNFα, IL-1B, Col1A1, aSMA, TGFβ, VEGFA, VEGFB, or any combination thereof in a subject. In some embodiments, administration of an anti-Gal3 antibody or its conjugate reduces the production of autoantibodies, such as anti-nucleic acid autoantibodies, in a subject. The inflammation may be pneumonia and may be associated with diseases including, but not limited to, COPD, pneumonitis, asthma, sarcoidosis, pulmonary fibrosis, histiocytosis, bronchiolitis obliterans, or any combination thereof. In some embodiments, the inflammation may be associated with an autoimmune disease, which includes, but is not limited to, systemic lupus erythematosus (SLE), Graves' disease, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, celiac disease, or any combination thereof.

[0014] Also disclosed herein are methods that reduce or inhibit the cleavage of CD62L, thereby reducing IL-8 production and / or cellular processes such as Gal3, MPO, GROα / KC, Ly6c1, INOS, IL-6, TNFα, IL-1B, Col1A1, aSMA, and T This method modulates the expression of GFβ, VEGFA, VEGFB, or any combination thereof. In some embodiments, the method includes contacting cells with an anti-Gal3 antibody or its conjugated fragment.

[0015] Also disclosed herein are pharmaceutical antibody preparations. In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of one or more of the antibodies disclosed herein. In some embodiments, the pharmaceutical antibody preparation further comprises histidine, methionine, NaCl, and polysorbate. In some embodiments, the pharmaceutical antibody preparation has a pH of 5.3 to 6.3.

[0016] Also disclosed herein are sterile vials containing any one of the pharmaceutical antibody preparations disclosed herein. In some embodiments, the sterile vial contains any one of the pharmaceutical antibody preparations disclosed herein in a concentrated form, which is intended to be diluted before administration of the pharmaceutical antibody preparation.

[0017] Embodiments of the pharmaceutical antibody preparations and sterile vials disclosed herein may be used in methods of treatment in subjects requiring treatment. In some embodiments, embodiments of the pharmaceutical antibody preparations and sterile vials disclosed herein are used in methods of treating coronavirus infection in subjects requiring treatment for coronavirus infection. In some embodiments, the coronavirus infection is SARS-related coronavirus infection. In some embodiments, the coronavirus infection is SARS-CoV-2 infection. In some embodiments, embodiments of the pharmaceutical antibody preparations and sterile vials disclosed herein are used in methods of reducing or inhibiting inflammation in subjects requiring reduction or inhibition of inflammation. In some embodiments, inflammation may be associated with inflammatory diseases, including but not limited to pneumonia, e.g., COPD, pneumonitis, asthma, sarcoidosis, pulmonary fibrosis, histiocytosis, bronchiolitis obliterans, or any combination thereof, or autoimmune diseases, e.g., systemic lupus erythematosus (SLE), Graves' disease, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, celiac disease, or any combination thereof. [Brief explanation of the drawing]

[0018] In addition to the features described above, further features and variations will be readily apparent from the drawings and the following description of exemplary embodiments. It should be understood that these drawings depict typical embodiments and are not intended to limit the scope. [Figure 1] Figure 1 depicts a graphical representation of relative Gal3 mRNA expression in normal individuals and COVID-19 patients. [Figure 2] Figure 2 depicts a graphical representation of the relative binding affinity of hACE2 proteins to Gal3 obtained from different vendors, as measured by ELISA. [Figure 3]Figure 3 depicts a graphical representation of the relative binding affinity of hCD147 protein to Gal3 obtained from different vendors, as measured by ELISA. [Figure 4] Figure 4 illustrates a graphical representation of the relative binding affinity of the SARS-CoV-2 protein spike (S) to Gal3, as measured by ELISA. [Figure 5A] Figure 5A illustrates a graphical representation of the evaluation of the relative binding affinity of hACE2 to Gal3 after blockade by an anti-Gal3 antibody, as measured by ELISA. [Figure 5B] Figure 5B depicts a graphical representation of the evaluation of the relative binding affinity of the SARS-CoV-2 protein spike (S) to Gal3 after blockade by anti-Gal3 antibody, as measured by ELISA. [Figure 6-1] Figure 6-1 depicts various embodiments of the sequences of human Gal3 (isoforms 1 and 3), ACE2, CD147, and the SARS-CoV-2 S protein. [Figure 6-2] Figure 6-2 depicts various embodiments of the sequences of human Gal3 (isoforms 1 and 3), ACE2, CD147, and the SARS-CoV-2 S protein. [Figure 7] Figure 7 depicts the Gal3 peptide used for the generation and binning of anti-Gal3 antibodies. [Figure 8] Figure 8 depicts a variable heavy chain CDR1 sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include one or more of the CDRs provided herein. [Figure 9] Figure 9 depicts a variable heavy chain CDR2 sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include one or more of the CDRs provided herein. [Figure 10]Figure 10 depicts a variable heavy chain CDR3 sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include one or more of the CDRs provided herein. [Figure 11] Figure 11 depicts a variable light chain CDR1 sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include one or more of the CDRs provided herein. [Figure 12] Figure 12 depicts a variable light chain CDR2 sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include one or more of the CDRs provided herein. [Figure 13] Figure 13 depicts a variable light chain CDR3 sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include one or more of the CDRs provided herein. [Figure 14-1] Figure 14-1 illustrates various exemplary combinations of heavy and light chain CDRs of anti-Gal3 antibodies. In some embodiments, any of the methods or compositions provided herein may include one or more of the heavy and light chain CDR combinations provided herein. [Figure 14-2] Figure 14-2 illustrates various exemplary heavy-chain and light-chain CDR combinations of anti-Gal3 antibodies. In some embodiments, any of the methods or compositions provided herein may include one or more of the heavy-chain and light-chain CDR combinations provided herein. [Figure 14-3] Figure 14-3 illustrates various exemplary heavy-chain and light-chain CDR combinations of anti-Gal3 antibodies. In some embodiments, any of the methods or compositions provided herein may include one or more of the heavy-chain and light-chain CDR combinations provided herein. [Figure 15-1]Figure 15-1 depicts the heavy chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VH regions. [Figure 15-2] Figure 15-2 depicts the heavy chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VH regions. [Figure 15-3] Figure 15-3 depicts the heavy chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VH regions. [Figure 15-4] Figure 15-4 depicts the heavy chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VH regions. [Figure 15-5] Figure 15-5 depicts the heavy chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VH regions. [Figure 15-6] Figure 15-6 depicts the heavy chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VH regions. [Figure 16-1] Figure 16-1 depicts the light chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VL regions. [Figure 16-2] Figure 16-2 depicts the light chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VL regions. [Figure 16-3]Figure 16-3 depicts the light chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VL regions. [Figure 16-4] Figure 16-4 depicts the light chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VL regions. [Figure 16-5] Figure 16-5 depicts the light chain variable region sequence of an exemplary anti-Gal3 antibody. In some embodiments, any method or composition provided herein may include any one of these VL regions. [Figure 17-1] Figure 17-1 depicts the heavy chain variable region and light chain variable region sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 17-2] Figure 17-2 depicts the heavy chain variable region and light chain variable region sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 17-3] Figure 17-3 depicts the heavy chain variable region and light chain variable region sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-1] Figure 18-1 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-2]Figure 18-2 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-3] Figure 18-3 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-4] Figure 18-4 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-5] Figure 18-5 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-6] Figure 18-6 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-7] Figure 18-7 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-8]Figure 18-8 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-9] Figure 18-9 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-10] Figure 18-10 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-11] Figure 18-11 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-12] Figure 18-12 depicts the heavy and light chain sequences of an exemplary anti-Gal3 antibody. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-13] Figures 18-13 depict the heavy and light chain sequences of exemplary anti-Gal3 antibodies. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-14]Figures 18-14 depict the heavy and light chain sequences of exemplary anti-Gal3 antibodies. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-15] Figures 18-15 depict the heavy and light chain sequences of exemplary anti-Gal3 antibodies. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 18-16] Figures 18-16 depict the heavy and light chain sequences of exemplary anti-Gal3 antibodies. In some embodiments, one or more VH / VL and / or CDR sequences provided in other figures can be paired with one or more relevant sequences provided herein. [Figure 19-1]Figure 19-1 depicts the alignment of the 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 alignments above use EU numbering. Residues identical to wild-type IgG1 are indicated by dots; gaps are indicated by hyphens. Sequences are explicitly given where they differ from the parent subtype of wild-type IgG1 or the σ variant. The white boxes below the alignments correspond to the International Immunogenetics Information System (IMGT) chain definitions. The boxes below the alignments correspond to the chain and helix secondary structure assignments for wild-type IgG1. Residues 267-273 form the BC loop, and 322-332 form the FG loop. Exemplary constant regions for human IgG quadruple chain (S228P mutant) and light chain (kappa) (SEQ ID NOs. 832-833) and mouse IgG2A (LALAPG and LALA mutants) (SEQ ID NOs. 838-839) are also provided. In some embodiments, one or more VH / VL and / or CDRs provided in other figures or otherwise disclosed herein may be paired with one or more of the exemplary constant regions provided herein. [Figure 19-2]Figure 19-2 depicts the alignment of the 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 alignments above use EU numbering. Residues identical to wild-type IgG1 are indicated by dots; gaps are indicated by hyphens. Sequences are explicitly given where they differ from the parent subtype of wild-type IgG1 or the σ variant. The white boxes below the alignments correspond to the International Immunogenetics Information System (IMGT) chain definitions. The boxes below the alignments correspond to the chain and helix secondary structure assignments for wild-type IgG1. Residues 267-273 form the BC loop, and 322-332 form the FG loop. Exemplary constant regions for human IgG quadruple chain (S228P mutant) and light chain (kappa) (SEQ ID NOs. 832-833) and mouse IgG2A (LALAPG and LALA mutants) (SEQ ID NOs. 838-839) are also provided. In some embodiments, one or more VH / VL and / or CDRs provided in other figures or otherwise disclosed herein may be paired with one or more of the exemplary constant regions provided herein. [Figure 20] Figure 20 depicts the antibody affinity (KD) of anti-Gal3 humanized antibodies IMT001 and IMT006a against human, cynomolgus monkey, and mouse Gal3. [Figure 21] Figure 21 depicts a graphical representation of body temperature in LPS-treated mice when further treated with either PBS control or the anti-Gal3 antibody IMT001. Mice treated with IMT001 experienced remission of LPS-induced hypothermia. [Figure 22A] Figure 22A illustrates the influence of Gal3 constructs (full-length wild-type, truncated, and P64H mutant Gal3) on neutrophil shedding in CD62L. [Figure 22B]Figure 22B illustrates the influence of the Gal3 construct (full-length wild-type, truncated, and P64H mutant Gal3) on IL-8 secretion. [Figure 23A] Figure 23A illustrates the effect of the exemplary anti-Gal3 antibody TB001 on the reversal of Gal3-induced shedding of CD62L by activated neutrophils. [Figure 23B] Figure 23B illustrates the effect of the exemplary anti-Gal3 antibody TB001 on the reversal of IL-8 secretion by activated neutrophils. [Figure 24A] Figure 24A illustrates the reduction of inflammation in a mouse model of inflammatory lung disease by an anti-Gal3 antibody. Figure 24A also illustrates the increased expression of Gal3 in bronchoalveolar fluid samples from a mouse model of chronic obstructive pulmonary disease (COPD). [Figure 24B-1] Figure 24B-1 depicts the reduction of inflammation in a mouse model of inflammatory lung disease by anti-Gal3 antibodies. Figure 24B depicts elevated levels of Gal3 and neutrophil count and function (Ly6c1, Kc, Inos), inflammatory cytokines (Il6, Tnfa, Il1b), and transcripts of genes associated with fibrosis (Col1A1, aSma, Tgfb, Vegfa, Vegfb) in lung tissue from a COPD mouse model compared to healthy tissue. Treatment with exemplary anti-Gal3 antibodies 2D10.2B2 and mTB001 resulted in reductions in these transcript levels in the COPD model. [Figure 24B-2] Figure 24B-2 depicts the reduction of inflammation in a mouse model of inflammatory lung disease by anti-Gal3 antibodies. Figure 24B depicts elevated levels of Gal3 and transcripts of genes associated with neutrophil count and function (Ly6c1, Kc, Inos), inflammatory cytokines (Il6, Tnfa, Il1b), and fibrosis (Col1A1, aSma, Tgfb, Vegfa, Vegfb) in lung tissue from a COPD mouse model compared to healthy tissue. Treatment with exemplary anti-Gal3 antibodies 2D10.2B2 and mTB001 resulted in a reduction of these transcript levels in the COPD model. [Figure 24C]Figure 24C depicts the reduction of inflammation in a mouse model of inflammatory lung disease by anti-Gal3 antibody. Figure 24C depicts the increase in neutrophil percentage and total number in lung tissue of a COPD model compared to healthy tissue, where treatment with exemplary anti-Gal3 antibody results in a reduction in neutrophil count. [Figure 24D] Figure 24D illustrates the reduction of inflammation in a mouse model of inflammatory lung disease by anti-Gal3 antibody. Figure 24D also illustrates the increased expression of myeloperoxidase (MPO) and keratinocyte-derived chemokines (KCs) in bronchoalveolar fluid samples from a COPD mouse model compared to healthy mice. Treatment with 2D10.2B2 and mTB001 reduced MPO expression, and 2D10.2B2 also had a significant effect in reducing KC expression in the disease model. [Figure 25] Figure 25 illustrates the reduction in anti-DNA autoantibody production following treatment with the exemplary anti-Gal3 antibody mbTB001 in a graft-versus-host disease mouse model. [Figure 26-1] Figure 26-1 illustrates the reduction in TNFα production by activated neutrophils under pro-inflammatory conditions following treatment with exemplary anti-Gal3 antibodies TB001 and TB006 compared to the control antibody MOPC21. [Figure 26-2] Figure 26-2 illustrates the reduction in TNFα production by activated neutrophils under pro-inflammatory conditions following treatment with exemplary anti-Gal3 antibodies TB001 and TB006 compared to the control antibody MOPC21. [Figure 26-3] Figure 26-3 illustrates the reduction in TNFα production by activated neutrophils under pro-inflammatory conditions following treatment with exemplary anti-Gal3 antibodies TB001 and TB006 compared to the control antibody MOPC21. [Figure 27-1] Figure 27-1 illustrates the reduction in IL-6 production by activated neutrophils under pro-inflammatory conditions following treatment with exemplary anti-Gal3 antibodies TB001 and TB006 compared to the control antibody MOPC21. [Figure 27-2]Figure 27-2 illustrates the reduction in IL-6 production by activated neutrophils under pro-inflammatory conditions following treatment with exemplary anti-Gal3 antibodies TB001 and TB006 compared to the control antibody MOPC21. [Figure 27-3] Figure 27-3 illustrates the reduction in IL-6 production by activated neutrophils under pro-inflammatory conditions following treatment with exemplary anti-Gal3 antibodies TB001 and TB006 compared to the control antibody MOPC21. [Figure 28] Figure 28 illustrates the antibody names used throughout this disclosure to refer to the same antibody (exemplary peptide and nucleic acid sequences are provided elsewhere in this disclosure and can be appropriately attributed to at least one of the names depicted), which may be used interchangeably. The names shown in the columns correspond to the same antibody. [Figure 29-1] Figure 29-1 depicts a nucleic acid sequence encoding an exemplary heavy chain variable region of an anti-Gal3 antibody disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-2] Figure 29-2 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-3] Figure 29-3 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-4]Figure 29-4 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-5] Figure 29-5 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-6] Figure 29-6 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-7] Figure 29-7 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-8] Figure 29-8 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-9] Figure 29-9 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-10]Figure 29-10 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-11] Figure 29-11 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 29-12] Figure 29-12 depicts nucleic acid sequences encoding exemplary heavy chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chain variable regions encoded by the nucleic acids provided herein. [Figure 30-1] Figure 30-1 depicts a nucleic acid sequence encoding an exemplary light chain variable region of an anti-Gal3 antibody disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chain variable regions encoded by the nucleic acids provided herein. [Figure 30-2] Figure 30-2 depicts a nucleic acid sequence encoding an exemplary light chain variable region of an anti-Gal3 antibody disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chain variable regions encoded by the nucleic acids provided herein. [Figure 30-3] Figure 30-3 depicts a nucleic acid sequence encoding an exemplary light chain variable region of an anti-Gal3 antibody disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chain variable regions encoded by the nucleic acids provided herein. [Figure 30-4]Figure 30-4 depicts nucleic acid sequences encoding exemplary light chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chain variable regions encoded by nucleic acids provided herein. [Figure 30-5] Figure 30-5 depicts nucleic acid sequences encoding exemplary light chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more light chain variable regions encoded by the nucleic acids provided herein. [Figure 30-6] Figure 30-6 depicts nucleic acid sequences encoding exemplary light chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more light chain variable regions encoded by the nucleic acids provided herein. [Figure 30-7] Figure 30-7 depicts nucleic acid sequences encoding exemplary light chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more light chain variable regions encoded by the nucleic acids provided herein. [Figure 30-8] Figure 30-8 depicts nucleic acid sequences encoding exemplary light chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any of the compositions or methods provided herein may include one or more light chain variable regions encoded by the nucleic acids provided herein. [Figure 30-9] Figure 30-9 depicts nucleic acid sequences encoding exemplary light chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chain variable regions encoded by nucleic acids provided herein. [Figure 30-10]Figure 30-10 depicts a nucleic acid sequence encoding an exemplary light chain variable region of an anti-Gal3 antibody disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chain variable regions encoded by the nucleic acids provided herein. [Figure 30-11] Figure 30-11 depicts a nucleic acid sequence encoding an exemplary light chain variable region of an anti-Gal3 antibody disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chain variable regions encoded by the nucleic acids provided herein. [Figure 30-12] Figure 30-12 depicts nucleic acid sequences encoding exemplary light chain variable regions of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chain variable regions encoded by nucleic acids provided herein. [Figure 31-1] Figure 31-1 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-2] Figure 31-2 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-3] Figure 31-3 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-4]Figure 31-4 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-5] Figure 31-5 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-6] Figure 31-6 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-7] Figure 31-7 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-8] Figure 31-8 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-9] Figure 31-9 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-10]Figure 31-10 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-11] Figure 31-11 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-12] Figure 31-12 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-13] Figure 31-13 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-14] Figure 31-14 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-15] Figure 31-15 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-16]Figure 31-16 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-17] Figure 31-17 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-18] Figure 31-18 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-19] Figure 31-19 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-20] Figure 31-20 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-21] Figure 31-21 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-22]Figure 31-22 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-23] Figure 31-23 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 31-24] Figure 31-24 depicts nucleic acid sequences encoding exemplary heavy chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more heavy chains encoded by nucleic acids provided herein. [Figure 32-1] Figure 32-1 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-2] Figure 32-2 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-3] Figure 32-3 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-4]Figure 32-4 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-5] Figure 32-5 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-6] Figure 32-6 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-7] Figure 32-7 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-8] Figure 32-8 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-9] Figure 32-9 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-10]Figure 32-10 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-11] Figure 32-11 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 32-12] Figure 32-12 depicts nucleic acid sequences encoding exemplary light chains of anti-Gal3 antibodies disclosed herein. In some embodiments, any composition or method provided herein may include one or more light chains encoded by nucleic acids provided herein. [Figure 33A] Figure 33A illustrates an exemplary alignment of the heavy chain CDR of an exemplary anti-Gal3 antibody disclosed herein. [Figure 33B] Figure 33B depicts an exemplary alignment of the light chain CDR of an exemplary anti-Gal3 antibody disclosed herein. [Modes for carrying out the invention]

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

[0020] Furthermore, Gal3 plays a crucial role in promoting the recruitment of leukocytes to the site of infection by pathogens, such as viruses. Increased cytokine release by leukocytes fighting viral infections can trigger cytokine release syndrome (CRS, or "cytokine storm"). CRS is a leading cause of fatal outcomes in patients infected with SARS-CoV-2 and other coronaviruses. Inhibition of Gal3 activity disrupts leukocyte recruitment and reduces levels of harmful cytokine production.

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

[0022] Some embodiments disclosed herein are antibodies specific to galectin-3 (Gal3) and their conjugated fragments, as well as methods of using them for the treatment or prevention of viral infections, such as SARS-CoV-2 infection, SARS-related coronavirus infection, or other coronavirus infections. The anti-Gal3 antibodies and their conjugated fragments disclosed herein interfere with the interaction between Gal3 and the SARS-CoV-2 spike (S) protein. The anti-Gal3 antibodies and their conjugated fragments disclosed herein also interfere with the interaction between Gal3 and host cell receptors that the virus uses to enter host cells, such as ACE2 and / or CD147. Also disclosed herein are methods of using anti-Gal3 antibodies and their conjugated fragments to reduce or inhibit toxicity resulting from cytokine release syndrome (CRS), which may occur as a result of respiratory viral infections, such as SARS-CoV-2 infection, as well as for the treatment of sequelae of viral infections, such as pulmonary fibrosis resulting from respiratory viral infections, such as SARS-CoV-2 infection.

[0023] Provided herein are anti-Gal3 antibodies or their conjugated fragments, as well as embodiments relating to methods for interfering with the interaction between Gal3 and a viral protein or host receptor protein, and their use therefor. In some embodiments, this interference is used to treat an ongoing viral infection. In some embodiments, the viral infection is a coronavirus infection. In some embodiments, the viral infection is a SARS-CoV-2 virus infection. In other embodiments, this interference is used to treat the after-effects of a previous viral infection.

[0024] In some embodiments, the method involves an antibody that binds to Gal3 and interferes with the interaction between Gal3 and another protein, such as a viral protein or a host receptor protein. This results in direct or indirect occlusion of the interaction region between Gal3 and the other protein, for example, a conformational change of Gal3, which in turn prevents it from binding to the other protein or from being active with the other protein. The binding can be such that it does not occur. This can also be a result of binding to a first section of Gal3, where a portion of the antibody interferes with or modifies the interaction between Gal3 and other proteins. In some embodiments, the first section of Gal3 is the N-terminal domain of Gal3, the tandem repeat domain (TRD) of Gal3, or the C-terminal domain of Gal3. In some embodiments, the antibody that binds to Gal3 does not bind to the C-terminal domain of Gal3.

[0025] In some embodiments, a method is provided for interfering with the interaction between Gal3 and a viral protein or host receptor protein. In some embodiments, the method involves contacting the interaction site between Gal3 and the viral protein or host receptor protein with an antibody or its binding fragment that selectively binds to Gal3 and interferes with the interaction between Gal3 and the viral protein or host receptor protein.

[0026] In some embodiments, methods are provided for using an anti-Gal3 antibody or a conjugated fragment thereof, or a composition comprising an anti-Gal3 antibody or a conjugated fragment thereof, to block or interfere with an interaction between Gal3 and another protein, either in vitro or in vivo. In some embodiments, the interaction is between Gal3 and a viral protein. In some embodiments, the viral protein is a coronavirus protein. In some embodiments, the viral protein is a SARS-CoV-2 protein. In some embodiments, the viral protein is a SARS-CoV-2 S, E, M, or HE protein. In some embodiments, the viral protein is a SARS-CoV-2 S protein. In some embodiments, the interaction is between Gal3 and a host receptor protein that the virus uses to enter a host cell. In some embodiments, the host receptor protein is a protein used by the coronavirus to enter a host cell. In some embodiments, the host receptor protein is a protein used by the SARS-CoV-2 virus to enter a host cell. In some embodiments, the host receptor protein is ACE2 and / or CD147. In some embodiments, a method of using an anti-Gal3 antibody or its conjugate fragment, or a composition containing an anti-Gal3 antibody or its conjugate fragment, to block or interfere with the interaction between Gal3 and another protein is used to treat, cure, or prevent a disease or disorder in a subject. In some embodiments, the disease or disorder is a viral infection, e.g., SARS-CoV-2 infection or other coronavirus infection. In some embodiments, the disease or disorder is a sequela of a previous viral (e.g., SARS-CoV-2 or other coronavirus) infection. In some embodiments, the sequela includes fibrosis, e.g., pulmonary fibrosis. In some embodiments, the anti-Gal3 antibody or its conjugate fragment is administered in combination with another antiviral or anti-inflammatory therapy. In some embodiments, the disease or disorder is CRS. In some embodiments, CRS is a result of a viral infection.In some embodiments, CRS is a result of SARS-CoV-2 infection or other coronavirus infection. In some embodiments, the disease or disorder is sepsis. In some embodiments, the disease or disorder is viral sepsis. In some embodiments, CRS is a result of sepsis caused by a viral infection. In some embodiments, CRS is a result of sepsis caused by SARS-CoV-2 infection or other coronavirus infection.

[0027] Also disclosed herein are methods for reducing or inhibiting inflammation in subjects where it is necessary to reduce or inhibit inflammation. In some embodiments, the method comprises administering an effective amount of anti-Gal3 antibody or a conjugated fragment thereof to the subject. The inflammation may or may not be associated with a viral infection, such as coronavirus infection. In some embodiments, the inflammation may be associated with a disease, such as an inflammatory disease or an autoimmune disease. For example, an inflammatory disease may be lung This may include inflammation, COPD, pneumonitis, asthma, sarcoidosis, pulmonary fibrosis, histiocytosis, bronchiolitis obliterans, or any combination thereof, or autoimmune diseases, such as systemic lupus erythematosus, Graves' disease, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, celiac disease, or any combination thereof. The inflammation may be associated with neutrophil activation and / or migration, and administration of an anti-Gal3 antibody or its conjugate fragment reduces or inhibits neutrophil activation and / or migration.

[0028] Additional aspects of this disclosure generally relate to pharmaceutically acceptable antibody preparations comprising an antibody that binds to Gal3 and one or more excipients, diluents, carriers, salts, and buffers. These pharmaceutically acceptable antibody preparations are used to treat diseases, e.g., infections caused by pathogens, e.g., viruses, and / or inflammation associated with the diseases described above or disclosed herein. In some embodiments, the pharmaceutically acceptable antibody preparation comprises one of the anti-Gal3 antibodies disclosed herein, histidine, methionine, NaCl, and polysorbate, and has a pH of 5.3 to 6.3. Also disclosed herein are sterile vials containing one of the pharmaceutically acceptable antibody preparations disclosed herein, which also include concentrated forms of the pharmaceutically acceptable antibody preparation intended to be diluted for administration.

[0029] Also disclosed herein are embodiments of methods for treating coronavirus infection, which include administering one of the pharmaceutical antibody preparations disclosed herein to a subject in need of treatment for coronavirus infection. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human.

[0030] definition In the following detailed description, the accompanying drawings forming parts of this application are referenced. In the drawings, similar symbols typically identify similar components unless otherwise specified by the context. The exemplary embodiments described in the detailed description, drawings, and claims are not intended to be limiting. Other embodiments may be used and other modifications may be made without departing from the spirit or scope of the subject matter presented herein. The aspects of this disclosure, as generally described herein and shown in the drawings, can be arranged, substituted, combined, separated, and designed in a variety of different configurations, all of which are expressly assumed herein.

[0031] Unless otherwise defined, scientific and technical terms used herein have the same meanings as those commonly understood by those skilled in the art to which this disclosure pertains. For the purposes of this disclosure, the following terms are defined below:

[0032] The articles "a" and "an" are used herein to refer to one or more (e.g., at least one) of the grammatical objects of the article. For example, "an" The term "element" refers to one or more elements.

[0033] "Approximately" means a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight, or length that varies by only about 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% relative to the reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight, or length.

[0034] Throughout this specification, unless otherwise required by the context, the words “comprise,” “comprises,” and “comprising” encompass the steps or elements or groups of steps or elements described, but do not exclude any other steps or elements or groups of steps or elements. It is understood that these implies: "consisting of" means including and being limited to any of the elements preceding the phrase "consisting of." Thus, the phrase "consisting of" indicates that the listed elements are required or mandatory, and that other elements may not be present. "essentially consisting of" means including any of the elements listed before the phrase, and being limited to other elements that do not interfere with or contribute to the activity or action of the listed elements as specified in this disclosure. Thus, the phrase "essentially consisting of" indicates that the listed elements are required or mandatory, while other elements are optional and may or may not be present, depending on whether they substantially affect the activity or action of the listed elements.

[0035] The term “coronavirus,” as used herein, refers to a family of enveloped, positive-sense, single-stranded RNA viruses that infect mammals and birds. In humans, coronavirus infections can cause mild symptoms such as the common cold, or more severe respiratory conditions, such as severe acute respiratory syndrome (SARS), acute respiratory distress syndrome (ARDS), cough, congestion, sore throat, shortness of breath, pneumonia, bronchitis, and hypoxia. Other symptoms include, but are not limited to, fever, fatigue, muscle aches, and gastrointestinal symptoms, such as vomiting, diarrhea, and abdominal pain. The viral envelope contains the spike ("S"), envelope ("E"), membrane ("M"), and hemagglutinin esterase ("HE") transmembrane structure proteins. The S protein contains a receptor-binding domain ("RBD"), which is a highly immunogenic region that determines the host receptor specificity of the viral lineage. The viral nucleocapsid contains multiple nucleocapsid ("N" or "NP") proteins that coat the RNA genome. During infection, the S protein attaches to a host cell receptor, initiating entry into the host cell via endocytosis or envelope membrane fusion. The RNA genome is translated by host ribosomes to produce new structural proteins and RNA-dependent RNA polymerase that replicates the viral genome. The viral particles are assembled in the host endoplasmic reticulum and shedged by Golgi-mediated exocytosis. Further information on the structure and infection cycle of coronaviruses can be found in Non-Patent Literature 1 (which is incorporated herein in its entirety by express reference).

[0036] The terms “SARS-CoV-2” and “2019-nCoV,” as used herein, refer to the lineage of coronaviruses that caused the human coronavirus disease 2019 (“COVID-19”) pandemic. Its transmissibility, long incubation period, and modern globalization have led to the worldwide spread of the virus. The development of SARS and other respiratory problems in infected individuals has resulted in immense stress on healthcare infrastructure. While testing is ongoing, there are currently no approved treatments or vaccines for SARS-CoV-2 and other coronaviruses in humans. Like the original SARS virus (SARS-CoV-1), SARS-CoV-2 infects human cells by binding to angiotensin-converting enzyme 2 (ACE2) via the RBD of its S protein. The SARS-CoV-2 virus may also enter host cells using the CD147 (basidine, EMMPRIN) host cell receptor. The embodiments disclosed herein may be applied to other coronaviruses, including but not limited to HCoV-229E, HCoV-OC43, SARS-CoV-1, HCoV NL63, HKU1, and MERS-CoV. An exemplary sequence of the SARS-CoV-2 spike (S) protein (NBCI reference number QHD43416.1) is shown in SEQ ID NO: 819. An exemplary sequence of human angiotensin-converting enzyme 2 (ACE2) is shown in SEQ ID NO: 820. An exemplary sequence of human CD147 (basidine, EMMPRIN) (NCBI reference number Q54A51) is shown in SEQ ID NO: 821.

[0037] The terms “sequela” or “sequelae” as used herein refer to conditions resulting from a previous illness, disability, or condition. This refers to a disease, disorder, or condition. Since coronaviruses, such as SARS-CoV-2, are respiratory viruses, lung complications are a common sequela of coronavirus infection. This includes pulmonary fibrosis and / or pulmonary edema. Other sequelae observed in patients with COVID-19 include, but are not limited to, other fibroses, cardiovascular diseases, thrombosis, neurological disorders, kidney diseases, or liver diseases.

[0038] The terms "cytokine release syndrome" (CRS) or "cytokine storm," as used herein, refer to the uncontrolled release of pro-inflammatory cytokines by immune cells, including T cells, natural killer cells, macrophages, dendritic cells, B cells, monocytes, neutrophils, leukocytes, and lymphocytes, in response to disease, infection, or immunotherapy. CRS is triggered by infectious stimuli, non-infectious stimuli, conditions, syndromes, or any combination thereof. Diseases or infections that can cause Cryopylinopathy include bacterial infections, viral infections, fungal infections, protozoan infections, graft-versus-host diseases, cytomegalovirus, Epstein-Barr virus, hemophagocytic lymphohistiocytosis (HLH), Epstein-Barr virus-associated HLH, sporadic HLH, macrophage activation syndrome (MAS), chronic arthritis, systemic juvenile idiopathic arthritis (sJIA), Still's disease, cryopyrin-associated periodic syndromes (CAPS), familial cold autoinflammatory syndrome (FCAS), familial cold urticaria (FCU), Macklewells syndrome (MWS), chronic neonatal neurocutaneous arthropathy (CINCA) syndrome, and cryopylinopathy including hereditary or de novo acquisition of functional mutations in the NLRP3 gene. This includes, but is not limited to, cryopyrinopathy, hereditary autoinflammatory disorders, acute pancreatitis, severe burns, trauma, acute respiratory distress syndrome (ARDS), streptococcus, pseudomonas, influenza, avian influenza, H5N1, H1N1, smallpox virus, coronavirus, severe acute respiratory syndrome (SARS), SARS-CoV-1, SARS-CoV-2, sepsis, gram-negative sepsis, gram-positive toxins, malaria, Ebola virus, smallpox virus, systemic gram-negative bacterial infections, bacteremia, Jarisch-Herxheimer syndrome, glycosylphosphatidylinositol (GPI), or lipopolysaccharides. Immunotherapy that may cause CRS includes, but is not limited to, rituximab, obinutuzumab, alemtuzumab, brentuximab, dacetuzumab, nivolumab, ceralizumab, oxaliplatin, lenalidomide, T-cell engager molecules, bispecific T-cell engager (BiTE) molecules, or CAR T therapies.CRS may be treated with anti-inflammatory therapies, including but not limited to anti-cytokine antibodies, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, corticosteroids, free radical scavengers, or TNF-α blockers.

[0039] As used herein, the term "cytokine" refers to small proteins, polypeptides, or peptides involved in inflammatory signaling, or proteins released by a population of cells that act as intercellular mediators to other cells or have an autocrine effect on protein-producing cells. Cytokines include chemokines, interferons, interleukins, lymphokines, monokines, tumor necrosis factor, CCL1, CCl2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CXCL1, CXCL2, and CXCL3. , CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL15, CXCL16, CXCL17, CX3CL1, XCL1, XCL2, I NFα, INFβ, INFγ, IL-1, IL-1a, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-1 7, IL-17A-F, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-3 0, IL-31, IL-32, IL-33, IL-34, IL-35, IL-36, IL-37, IL-38, aldesleukin, GM-CSF, TNFα, TNFβ, TNFγ, TGF-I-3 This includes, but is not limited to, TNFSF4, TNFSF5, TNFSF6, TNFSF7, TNFSF8, TNFSF9, TNFSF10, TNFSF11, TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18, or TNFSF19, leukemia inhibitor (LIF), ciliary neurotrophic factor (CNTF), CNTF-like cytokine (CLC), cardiotrophin (CT), Kit ligand (KL), or any combination thereof.

[0040] As used herein, the terms “individual,” “subject,” and “patient” mean any mammal. In some embodiments, the mammal is human. In some embodiments, the mammal is non-human. None of the terms require, or are not limited to, a situation characterized by supervision (e.g., constant or intermittent) of a healthcare professional (e.g., physician, registered nurse, nurse practitioner, physician assistant, or hospice worker).

[0041] As used herein, the terms “polypeptide,” “peptide,” and “protein” are interchangeable herein to refer to polymers of amino acids of any length. The polymers may be linear, cyclic, or branched, and may contain modified amino acids or have non-amino acids interspersed. The terms also encompass amino acid polymers modified, for example, through sulfation, glycosylation, lipidation, acetylation, phosphorylation, iodization, 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 labeled component.

[0042] As used herein, the term “amino acid” refers to natural and / or unnatural or synthetic amino acids, including glycine and both D and L optical isomers, and amino acid analogs and peptide mimics.

[0043] A polypeptide or amino acid sequence "derived" from a specified protein refers to the origin of the polypeptide. Preferably, the polypeptide has an amino acid sequence that is essentially identical to the polypeptide encoded in the sequence, or to the amino acid sequence of that portion consisting of at least 10-20 amino acids, at least 20-30 amino acids, or at least 30-50 amino acids, or is immunologically identifiable using the polypeptide encoded in the sequence. This scientific term also includes polypeptides expressed from a specified nucleic acid sequence.

[0044] As used herein, the term “antibody” is intended to include any polypeptide chain-containing molecular structure having a specific shape that fits and recognizes an epitope, wherein one or more non-covalent interactions stabilize the complex between the molecular structure and the epitope. The antibodies used in the present invention may be polyclonal antibodies, but monoclonal antibodies are preferred because they are regenerative by cell culture or recombination and can be modified to reduce their antigenicity.

[0045] In addition to whole immunoglobulins (or their recombinant counterparts), immunoglobulin fragments or "binding fragments" containing epitope binding sites (e.g., Fab', F(ab')2, one) are also included. Variable chain fragments (scFv), diabodies, minibodies, nanobodies, single-domain antibodies (sdAb), or other fragments are useful as antibody moieties in the present invention. Such antibody fragments may be generated from whole immunoglobulins by cleavage with lysine, pepsin, papain, or other proteases. Miniature immunoglobulins may be designed using recombinant immunoglobulin technology. For example, "Fv" immunoglobulins for use in the present invention may be produced by linking a variable light chain region to a variable heavy chain region via a peptide linker (e.g., polyglycine or another sequence that does not form either an alpha-helix or a beta-sheet motif). Nanobodies or single-domain antibodies may also be derived from alternative organisms, such as dromedary camels, camels, llamas, alpacas, or sharks. In some embodiments, the antibody may be a conjugate, such as a pegylated antibody, drug, radioisotope, or toxin conjugate. Monoclonal antibodies directed against specific epitopes or combinations of epitopes enable the targeting and / or depletion of cell populations expressing markers. Various techniques can be used to screen cell populations expressing markers using monoclonal antibodies, and these techniques include magnetic separation using antibody-coated magnetic beads, "panning" with antibodies attached to a solid matrix (i.e., a plate), and flow cytometry (e.g., Patent Document 3; the whole is incorporated herein by express reference).

[0046] As is well known in the art, the term “Fc region” is used to define the C-terminal region of an immunoglobulin heavy chain. The “Fc region” may be a native sequence Fc region or a variant Fc region. While the boundaries of the Fc region of an immunoglobulin heavy chain can vary, the human IgG heavy chain Fc region is typically defined as extending from an amino acid residue at position Cys226, or Pro230, to its carboxyl terminus. The numbering of residues within the Fc region is the EU index numbering, as in Kabat. Non-patent literature 2. The Fc region of an immunoglobulin generally contains two constant domains, CH2 and CH3. As is well known in the art, the Fc region can exist in dimeric or monomeric form.

[0047] As is well known in the art, the "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.

[0048] The “variable region” of an antibody refers to the variable region of the antibody light chain or the variable region of the antibody heavy chain, either alone or in combination. As is known in the art, each of the variable regions of the heavy and light chains consists of four framework regions (FRs) connected by three complementarity-determining regions (CDRs), also known as hypervariable regions, and contributes to the formation of the antibody's antigen-binding site. When a variant of the target variable region, particularly a variant having substitutions in amino acid residues outside the CDR region (i.e., within the framework region), is desired, a suitable amino acid substitution, preferably a conserved amino acid substitution, can be identified by comparing the target variable region with the variable regions of other antibodies containing the same canonical class of CDR1 and CDR2 sequences as the target variable region (Non-Patent Literature 3).

[0049] In certain embodiments, definitive range determination of the CDR and identification of residues constituting the antibody binding site are achieved by elucidating the structure of the antibody and / or the structure of the antibody-ligand complex. In certain embodiments, this can be achieved by any of the various techniques known to those skilled in the art, e.g., X-ray crystallography. In certain embodiments, the CDR region can be identified or estimated using various analytical methods. Examples of such methods include the Kabat definition, the Chothia definition, the IMGT approach (Non-Patent Literature 4), computer programs such as Paratome (Non-Patent Literature 5), the AbM definition, and the conformational definition. This includes, but is not limited to, the definition of ().

[0050] The Kabat definition is a standard for numbering residues in antibodies and is typically used to identify CDR regions. See, for example, Non-Patent Document 6. The Chothia definition is similar to the Kabat definition, but takes into account the location of a specific structural loop region. See, for example, Non-Patent Document 7. The AbM definition uses an integrated set of computer programs developed by the Oxford Molecular Group to model antibody structures. See, for example, Non-Patent Document 8. The AbM definition models the tertiary structure of an antibody from its primary sequence using a combination of a knowledge database and the ab initio method, as described in, for example, Non-Patent Document 9. The contact definition is based on the analysis of available complex crystal structures. See, for example, Non-Patent Document 10. In another approach, referred herein as the “conformation definition” of CDRs, the location of a CDR may be identified as a residue that contributes enthalpily to antigen binding. See, for example, Non-Patent Document 11. Furthermore, other CDR boundary definitions may not strictly adhere to one of the approaches described above, but nevertheless overlap with at least a portion of the Kabat CDR, however they may be shortened or extended in light of predictions or experimental findings that certain residues or groups of residues do not significantly affect antigen binding. As used herein, CDR can refer to a CDR defined by any of the approaches known in the art, encompassing combinations of these approaches. Methods used herein may utilize CDRs defined according to any of these approaches. For any given embodiment containing more than one CDR, a CDR may be defined according to any of the Kabat, Chothia, extended, IMGT, Paratome, AbM, and / or conformational definitions, or any combination of the above.

[0051] Where disclosed herein, sequences having identity % (% identity) to any of the sequences disclosed herein are assumed and may be used. The term "identity %" (% identity) refers to the percentage of units (i.e., amino acids or nucleotides) that are the same between two or more sequences compared to their lengths. If the two or more sequences being compared are the same length, identity % is their respective lengths. If the two or more sequences being compared are of different lengths, deletions and / or insertions may be introduced to obtain the best alignment. In some embodiments, these sequences may include peptide sequences, nucleic acid sequences, CDR sequences, variable region sequences, or heavy or light chain sequences. In some embodiments, any sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with any of the sequences disclosed herein may be used. In some embodiments, any sequence having at least 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 substitutions, deletions, or additions compared to any of the sequences disclosed herein may be used. Changes in the sequence may be applied, for example, to a single amino acid, a single nucleic acid base, or a nucleic acid codon; differences in longer sequences are also conceivable. When applied to antibody sequences, these differences in the sequence may be applied to antigen-binding regions (e.g., CDRs) or regions that do not bind to the antigen or are only secondary to antigen binding (e.g., framework regions).

[0052] If disclosed herein, homology %( Sequences having % homology are assumed and may be used. The term "% homology" refers to the degree of conservation between two sequences when their three-dimensional structures are taken into account. For example, homology between two protein sequences may depend on the distribution of structural motifs, such as beta strands, alpha helices, and other folds, as well as their distribution throughout the sequence. Homology may be determined through structural determination, either empirically or in silico. In some embodiments, any sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology to any of the sequences disclosed herein may be used. In some embodiments, any sequence having at least 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 substitutions, deletions, or additions compared to any of the sequences disclosed herein, which may or may not affect the overall homology %.

[0053] Where applicable in this specification, sequences having a certain percentage of similarity to any of the sequences disclosed herein may be assumed and used. In some embodiments, these sequences may include peptide sequences, nucleic acid sequences, CDR sequences, variable region sequences, or heavy or light chain sequences. As understood in the art with respect to peptide sequences, “similarity” refers to a comparison of amino acids based on their properties, which include, but are not limited to, size, polarity, charge, pK, aromaticity, hydrogen bonding properties, or the presence of functional groups (e.g., hydroxyl, thiol, amine, and carboxyl). The term “similarity%” (% similarity) refers to the percentage of units (i.e., amino acids) that are the same between two or more sequences compared to their lengths. If the two or more sequences being compared are the same length, the similarity% is their respective lengths. If the two or more sequences being compared are different lengths, deletions and / or insertions may be introduced to obtain the best alignment. The similarity of two amino acids may determine whether a particular substitution is conserved or non-conserved. Methods for determining the conservation of amino acid substitutions are generally known in the art and may involve substitution matrices. Commonly used substitution matrices include BLOSUM45, BLOSUM62, BLOSUM80, PAM100, PAM120, PAM160, PAM200, and PAM250, but other substitution matrices or approaches may be used where deemed appropriate by those skilled in the art. Certain substitution matrices may be preferred over others when considering aspects such as stringency, conservation and / or differences of related sequences (e.g., within the same species or broader), and the length of the sequence in question. As used herein, a peptide sequence having a certain percentage of similarity to another sequence has up to that percentage of amino acids that are identical or contain acceptable substitutions as defined by the similarity determination method used.In some embodiments, sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to any of the sequences disclosed herein may be used. In some embodiments, any sequence having at least 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 similar substitutions compared to any of the sequences disclosed herein may be used. When applied to an antibody sequence, these similar substitutions may not bind to the antigen-binding region (i.e., CDR) or the antigen. Alternatively, it can be applied to regions that are only secondary to antigen binding (i.e., framework regions).

[0054] When used herein in relation to sequences, the term “consensus sequence” refers to a generalized sequence that represents all different combinations of acceptable amino acids at each position in a group of sequences. A consensus sequence can provide insight into conserved regions of a related sequence where units (e.g., amino acids or nucleotides) are the same for most or all of the sequence, and into regions where the sequences differ. In the case of antibodies, the consensus sequence of a CDR may point to amino acids that are important or not necessarily required for antigen binding. A consensus sequence may be constructed using any of the sequences provided herein, and it is assumed that the various resulting sequences derived from a consensus sequence may be validated for having a similar effect to the template sequence.

[0055] When used herein in relation to antibodies, the term “compete” means that a first antibody, or its antigen-binding moiety, binds to an epitope in a manner sufficiently similar to the binding of a second antibody, or its antigen-binding moiety, and as a result, the binding of the first antibody to that cognitive epitope is detectedly reduced in the presence of the second antibody compared to the binding of the first antibody in the absence of the second antibody. An alternative event may occur in which the binding of the second antibody to its epitope is also detectedly reduced in the presence of the first antibody, but this is not necessary. That is, the first antibody can inhibit the binding of the second antibody to its respective epitope without inhibiting the binding of the first antibody to that epitope. However, if each antibody detectably inhibits the binding of the other antibody to its cognitive epitope or ligand, to the same, greater, or lesser degree, the antibodies are said to “cross-compete” with each other for the binding of their respective epitopes. Both competitive and cross-competitive 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), those skilled in the art will understand, based on the teachings provided herein, that such competitive and / or cross-competitive antibodies are encompassed and may be useful for the methods disclosed herein.

[0056] Antibodies that “preferentially bind” or “specifically bind” (as used interchangeably herein) to an epitope are well understood terms in the art, and methods for determining such specific or preferential binding are also well known in the art. A molecule is said to exhibit “specific binding” or “preferential binding” if it reacts or associates with a particular cell or substance more frequently, and / or more quickly, and / or for a longer duration and / or with higher affinity than with alternative cells or substances. An antibody “specifically binds” or “preferentially binds” to a target if it binds with higher affinity, and / or avidity, and / or more easily and / or for a longer 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 to that epitope with higher affinity, and / or avidity, and / or more easily and / or for a longer duration than it binds to other CFD epitopes or non-CFD epitopes. For example, it can also be understood from reading this definition that an antibody (or partial or epitope) that specifically or preferentially binds to a first target may or may not specifically or preferentially bind to a second target. Therefore, "specific binding" or "preferential binding" does not necessarily require exclusive binding (although it may include exclusive binding). While not always the case, generally, references to binding imply preferential binding.

[0057] As used herein, the term "antigen-binding molecule" refers to an antigen-binding portion that binds to an antigen, and optionally, a conjugate that facilitates the binding of the antigen-binding portion to the antigen-binding portion. This refers to a molecule containing a scaffold or framework portion that enables maceration or provides some additional properties to the antigen-binding molecule. In some embodiments, the antigen is Gal3. In some embodiments, the antigen-binding portion includes at least one CDR from an antibody that binds to the antigen. In some embodiments, the antigen-binding portion includes all three CDRs from the heavy chain of the antibody that binds to the antigen or from the light chain of the antibody that binds to the antigen. In some embodiments, the antigen-binding portion includes all six CDRs from the 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.

[0058] Non-exclusive examples of antigen-binding molecules include antibodies, antibody fragments (e.g., antigen-binding fragments of antibodies), antibody derivatives, and antibody analogs. Further specific examples include, but are not limited to, single-strand variable fragments (scFv), nanobodies (e.g., VH domains of camelid heavy-chain antibodies; VHH fragments, see Non-Patent Literature 12), Fab fragments, Fab' fragments, F(ab')2 fragments, Fv fragments, Fd fragments, and complementarity-determining region (CDR) fragments. These molecules may originate from any mammalian source, e.g., humans, mice, rats, rabbits, pigs, dogs, cats, horses, donkeys, guinea pigs, goats, or camelids. Antibody fragments may compete with intact antibodies for binding to target antigens, and fragments may be produced by modifying intact antibodies (e.g., enzymatic or chemical cleavage) or synthesized de novo using recombinant DNA technology or peptide synthesis. The antigen-binding molecule may include, for example, an alternative protein scaffold or an artificial scaffold having a grafted CDR or CDR derivative. Such scaffolds include, but are not limited to, antibody-derived scaffolds, including mutations introduced to stabilize the three-dimensional structure of the antigen-binding molecule, as well as entirely synthetic scaffolds, for example, those containing biocompatible polymers. See, for example, Non-Patent Document 13; Non-Patent Document 14. In addition, besides peptide antibody mimes ("PAMs"), antibody mimeograph-based scaffolds utilizing fibronectin components as scaffolds may be used.

[0059] Antigen-binding molecules can also include proteins containing one or more antibody fragments incorporated into a single polypeptide chain or multiple polypeptide chains. For example, antigen-binding molecules may include, but are not limited to, diabodies (see, e.g., Patent Document 4; Patent Document 5; and Non-Patent Document 15); intrabodies; domain antibodies (a single VL or VH domain or two or more VH domains joined by a peptide linker; see Non-Patent Document 16); maxibodies (two scFv fused to an Fc region; see Non-Patent Documents 17 and 18); triabodies; tetrabodies; minibodies (scFv fused to a CH3 domain; see Non-Patent Document 19); peptidebodies (one or more peptides attached to an Fc region; see Patent Document 6); linear antibodies (a pair of tandem Fd segments (VH-CH1-VH-CH1) that form a pair of antigen-binding regions together with a complementary light chain polypeptide; see Non-Patent Document 20); small modular immunopharmaceuticals (see Patent Document 7); and immunoglobulin fusion proteins (e.g., IgG-scFv, IgG-Fab, 2scFv-IgG, 4scFv-IgG, VH-IgG, IgG-VH, and Fab-scFv-Fc).

[0060] In certain embodiments, the antigen-binding molecule may have, for example, the structure of an immunoglobulin. An "immunoglobulin" is a tetrameric molecule, each tetramer containing two identical pairs of polypeptide chains, each pair having one "light" chain (approximately 25 kDa) and one "heavy" chain (approximately 50-70 kDa). The amino-terminal portion of each chain contains a variable region of approximately 100-110 or more amino acids, which is the main cause of antigen recognition. The carboxyl-terminal portion of each chain defines a constant region, which is the main cause of effector function.

[0061] Unless otherwise specified, the complementary definition areas disclosed herein conform to the IMGT definitions. In some embodiments, CDR may instead be defined by Kabat, Chothia, or other definitions approved by those skilled in the art.

[0062] As used herein, the term “humanized” when applied to non-human (e.g., rodent or primate) antibodies means a hybrid immunoglobulin, immunoglobulin chain or fragment thereof containing the smallest sequence derived from a non-human immunoglobulin.

[0063] As used herein, the terms “to treat” or “treatment” mean (as is commonly understood in the art) an approach to obtain a beneficial or desired outcome in the condition of the subject, encompassing clinical outcomes. Beneficial or desired clinical outcomes may include, but are not limited to, reduction or remission of one or more symptoms or conditions, a decrease in the severity of the disease, stabilization of the disease condition (i.e., prevention of exacerbation), prevention of transmission or spread of the disease, delay or slowing of disease progression, remission or temporary relief of the disease condition, reduction of disease recurrences, and improvement, whether partial or overall, and whether detectable or undetectable. “To treat” and “treatment” also include prophylactic treatment as used herein. A treatment method involves administering a therapeutically effective amount of an activator to the subject. The administration step may consist of a single dose or a series of doses. The composition is administered to the subject in an amount and duration sufficient to treat the patient. The duration of treatment depends on various factors, such as the severity of the condition, the patient's age and genetic profile, the concentration of the activator, the activity of the composition used in the treatment, or a combination thereof. It is also understood that the effective dosage of the agent used for treatment or prevention may be increased or decreased over the course of a particular treatment or prevention regime. Changes in dosage may be made and revealed by standard diagnostic assays known in the art. In some embodiments, chronic administration may be required.

[0064] The terms “effective amount” or “effective dose,” when used herein, have their declarative and ordinary meanings as understood in light of this specification and refer to the amount of the described composition or compound that results in an observable specified effect. The actual dose level of the active ingredient in the active composition of the subject matter of this disclosure can be modified to administer an effective amount of the active composition or compound to achieve a specified response for a particular subject and / or application. The selected dose level can vary based on a variety of factors, including, but not limited to, the activity of the composition, formulation, route of administration, combination with other drugs or treatments, the severity of the condition being treated, and the physical condition and medical history of the subject being treated. In some embodiments, a minimum dose is administered, and the dose is gradually increased to the minimum effective amount in the absence of dose-limiting toxicity. In addition to determining and adjusting the effective dose, evaluation of the timing and method of making such adjustments is assumed herein.

[0065] In some non-limiting embodiments, the effective amount or effective dose of the composition or compound may relate to an amount or dose that provides a significant, measurable, or sufficient therapeutic effect for the treatment of coronavirus infection, e.g., SARS-CoV-2 infection. In some embodiments, the effective amount or effective dose of the composition or compound may treat, induce remission of, or prevent the progression of inflammation, shortness of breath, fatigue, lung injury, or other symptoms associated with coronavirus infection, e.g., SARS-CoV-2 infection. In some embodiments, the effective amount or effective dose of the composition or compound may treat, induce remission of, or prevent the progression of pneumonic diseases, e.g., COPD, or autoimmune diseases, e.g., systemic lupus erythematosus. In some embodiments, the effective amount or effective dose of the composition or compound may relate to inflammation (associated with viral or other pathogenic infections). It may also treat, alleviate, or prevent the progression of the symptoms and / or causes (including neutrophil activation and migration) (which may be absent).

[0066] The term "administer" includes oral administration, topical contact, administration as a suppository, intravenous, intraperitoneal, intramuscular, intrafocal, intrathecal, intranasal, or subcutaneous administration to a subject, or implantation of a delayed-release device, such as a mini-osmosis pump. Administration is made by any of the following routes, which include parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, transnasal, transvaginal, rectal, or transdermal) administration. Parenteral administration includes, for example, intravenous, intramuscular, intraarteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial administration. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, and transdermal patches. "Combined administration" means that the first compound described herein is administered concurrently with, immediately before, or immediately after the administration of the second compound described herein.

[0067] As used herein, the term “therapeutic target” means a gene or gene product that can provide modulation of a disease phenotype by modulation of its activity (e.g., by modulation of expression and biological activity). As used throughout this specification, “modulation” means an increase or decrease in the phenomenon being referred to (e.g., modulation of biological activity means an increase or decrease in biological activity).

[0068] As used herein, “pharmaceutically acceptable” means carriers, excipients, and / or stabilizers that have their declarative and ordinary meanings as understood herein, and are nontoxic to cells or mammals to which they are exposed at the dosage and concentration used. “pharmaceutically acceptable,” “diluents,” “excipients,” and / or “carriers” have their declarative and ordinary meanings as understood herein, and are intended to include any and all solvents, dispersion media, coatings, antimicrobial and antifungal agents, as well as isotonic and absorption retardants, etc., that are suitable for administration to human, cat, dog, or other vertebrate hosts. Typically, pharmaceutically acceptable diluents, excipients, and / or carriers are diluents, excipients, and / or carriers that are approved by a federal, state, or other regulatory body, or are listed in the United States Pharmacopeia or other commonly recognized pharmacopoeias for use in animals, including non-human mammals, such as cats and dogs, in addition to humans. The terms diluent, excipient, and / or carrier may refer to a diluent, adjuvant, excipient, or vehicle with which a pharmaceutical preparation is administered. Such pharmaceutical diluents, excipients, and / or carriers may be sterile liquids, such as water and oil, including those of petroleum, animal, plant, or synthetic origin. Water, saline solutions, and aqueous dextrose and glycerol solutions may be used as liquid diluents, excipients, and / or carriers, particularly for injectable solutions. Suitable pharmaceutical diluents and / or excipients include sugars, starches, glucose, fructose, lactose, sucrose, maltose, gelatin, malt, rice, wheat flour, chalk, silica gel, sodium stearate, glyceryl monostearate, talc, salts, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, and ethanol, among others. A non-limiting example of a physiologically acceptable carrier is an aqueous pH buffered solution.A physiologically acceptable carrier may also contain one or more of the following: antioxidants, e.g., ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins, e.g., serum albumin; gelatin; immunoglobulins; hydrophilic polymers, e.g., polyvinylpyrrolidone; amino acids; carbohydrates, e.g., glucose, mannose, or dextrin; chelating agents, e.g., EDTA; sugar alcohols, e.g., glycerol, erythritol, trethitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fusitol, iditol, inositol, isomalt. Maltitol or lactitol, salt-forming counterions, such as sodium, and nonionic surfactants, such as TWEEN®, polyethylene glycol (PEG), and PLURONIC® S. The formulation may also contain, if desired, trace amounts of wetting agents, fillers, emulsifiers, or pH buffers. These formulations may take the form of solutions, suspensions, emulsions, and sustained-release formulations. The formulation should be suitable for the mode of administration.

[0069] The term “pharmaceutically acceptable salt” has its declarative and ordinary meaning as understood in light of this specification and includes, without limitation, relatively non-toxic inorganic and organic acid or base addition salts of compositions or excipients, including analgesics, therapeutic agents, and other materials. Examples of pharmaceutically acceptable salts include those derived from mineral acids, such as hydrochloric acid and sulfuric acid, and organic acids, such as ethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid. Examples of suitable inorganic bases for salt formation include ammonia, sodium, lithium, potassium, calcium, magnesium, aluminum, and zinc hydroxides, carbonates, and bicarbonates. Salts may also be formed with suitable organic bases, the organic bases including those that are non-toxic and sufficiently strong to form such salts. For example, such a class of organic bases may include, but is 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; and trihydroxymethylaminoethane.

[0070] As used herein, “carrier” refers to a compound, particle, solid, semi-solid, liquid, or diluent that facilitates the passage, delivery, and / or integration of a compound into cells, tissues, and / or organs of the body. For example, without limitation, lipid nanoparticles (LNPs) are a type of carrier that encapsulates oligonucleotides, thereby protecting the oligonucleotides from degradation during passage through the bloodstream and / or facilitating delivery to desired organs, such as the lungs.

[0071] As used herein, “diluent” refers to a component in a pharmaceutical composition that lacks pharmacological activity but may be pharmaceutically necessary or desirable. For example, a diluent may be used to increase the volume of a potent drug whose mass is too small for production and / or administration. It may also be a liquid for dissolving a drug administered by injection, ingestion, or inhalation. A common form of diluent in the art is a buffered aqueous solution, for example, phosphate-buffered saline that mimics the composition of human blood, without limitation.

[0072] The term “excipient” has its ordinary meaning as understood in light of this specification and refers, without limitation, to an inert substance, compound, or material added to a pharmaceutical composition to provide the composition with volume, consistency, stability, binding ability, lubricity, disintegration ability, etc. Excipients with desirable properties include preservatives, adjuvants, stabilizers, solvents, buffers, diluents, solubilizers, detergents, surfactants, chelating agents, antioxidants, alcohols, ketones, aldehydes, ethylenediaminetetraacetic acid (EDTA), citric acid, salts, sodium chloride, sodium bicarbonate, sodium phosphate, sodium borate, sodium citrate, potassium chloride, potassium phosphate, magnesium sulfate, sugars, dextrose, dextran, fructose, mannose, lactose, galactose, sucrose, sorbitol, cellulose, methylcellulose, hydroxypropyl methylcellulose (hypromellose), glycerin, polyvinyl alcohol, povidone, propylene glycol, serum, amino acids, polyethylene glycol, polysorbate 20, and poly The excipients may be found in the pharmaceutical composition in weight percentages within the range defined by a percentage of w / w of 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%, or any two of the above numbers.

[0073] Additional excipients with desirable properties include preservatives, adjuvants, stabilizers, solvents, buffers, diluents, solubilizers, detergents, surfactants, chelating agents, antioxidants, alcohols, ketones, aldehydes, ethylenediaminetetraacetic acid (EDTA), tris(hydroxymethyl)aminomethane (Tris), citric acid, ascorbic acid, acetic acid, salts, phosphates, citrates, acetates, succinates, chlorides, bicarbonates, borates, sulfates, sodium chloride, sodium bicarbonate, sodium phosphate, sodium borate, sodium citrate, potassium chloride, potassium phosphate, magnesium sulfate, sugars, dextrose, dextran 40, fructose, mannose, lactose, trehalose, galactose, sucrose, sorbitol, mannitol, cellulose, blood This includes, but is not limited to, pure 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 residues or impurities from the production process, including but not limited to serum, albumin, ovalbumin, antibiotics, inactivators, formaldehyde, glutaraldehyde, β-propiolactone, gelatin, cell debris, nucleic acids, peptides, amino acids, or growth medium components, or any combination thereof.The amount of excipients may be found in the formulation in weight percentages within the range defined by a percentage of at least 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%, or 100% w / w, or any two of the numbers above.

[0074] The term “adjuvant,” as used herein, refers to a substance, compound, or material administered in combination with an immunogenic antigen, epitope, or composition to stimulate an immune response and increase the effectiveness of protective immunity. Adjuvants help improve the immune response by enabling the continuous release of antigens, upregulation of cytokines and chemokines, recruitment of cells at the site of administration, increased antigen uptake and presentation in antigen-presenting cells, or activation of antigen-presenting cells and inflammasomes. Commonly used adjuvants include alum, aluminum salts, aluminum sulfate, aluminum hydroxide, aluminum phosphate, calcium hydroxide phosphate, potassium aluminum sulfate, oils, mineral oil, paraffin oil, oil-in-water emulsions, detergents, MF59, squalene, AS03, α-tocopherol, polysorbate 80, AS04, monophosphoryl lipid A, virosomals, nucleic acids, polyinosinic acid: polycytidylic acid, saponins, QS-21, proteins, flagellin, cytokines, chemokines, IL-1, IL-2, IL-12, IL-15, IL-21, imidazoquinoline, CpG oligonucleotides, lipids, phospholipids, and dihydrogen-11. This includes, but is not limited to, leoyl phosphatidylcholine (DOPC), trehalose dimycolic acid, peptidoglycan, bacterial extract, lipopolysaccharide, or Freund's adjuvant, or any combination thereof.

[0075] The term “purity” of any given substance, compound, or material, as used herein, refers to the actual amount of the substance, compound, or material compared to the expected amount. For example, a substance, compound, or material may be at least 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% pure, encompassing all decimals in between. Purity may be affected by undesirable impurities, which include, but are not limited to, by-products, isomers, enantiomers, decomposition products, solvents, carriers, vehicles, or contaminants, or any combination thereof. Purity may be measured by techniques including, but not limited to, chromatography, liquid chromatography, gas chromatography, spectroscopy, UV-Vis spectroscopy, infrared spectroscopy, mass spectrometry, nuclear magnetic resonance, gravimetric measurement, or titration, or any combination thereof.

[0076] The term "immune cells" refers to hematopoietic cells involved in the specific recognition of antigens. Immune cells include antigen-presenting cells (APCs), such as dendritic cells or macrophages, B cells, T cells, natural killer cells, and myeloid cells, such as monocytes, macrophages, eosinophils, mast cells, basophils, and granulocytes.

[0077] The term “immune response” refers to T cell-mediated and / or B cell-mediated immune responses. Exemplary immune responses include B cell responses (e.g., antibody production), T cell responses (e.g., cytokine production and cytotoxicity), and activation of cytokine-responsive cells, e.g., macrophages. The term “activate an immune response” refers to enhancing the level of a T cell-mediated and / or B cell-mediated immune response using methods known to those skilled in the art. In one embodiment, the level of enhancement is at least 20–50%, alternatively at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 120%, at least 150%, or at least 200%.

[0078] Where used herein, the terms “standard treatment,” “best practice,” and “standard therapy” refer to a treatment that a physician has recognized as appropriate, suitable, effective, and / or widely used for a particular disease. Standard treatment for a particular disease depends on many different factors, including the biological effect of the treatment, the area or location within the body, the patient’s condition (e.g., age, weight, sex, genetic risk, other disorders, secondary conditions), toxicity, metabolism, bioaccumulation, therapeutic index, dosage, and other factors known in the art. Determining standard treatment for a disease also depends on regulatory bodies, such as the US Food and Drug Administration and the International Food and Drug Administration. 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 Safety and efficacy are established in clinical trials standardized by Food and Drug Safety and the World Health Organization. Standard treatment for the disease may include, but is not limited to, surgery, radiation, chemotherapy, targeted therapy, or immunotherapy.

[0079] The terms "% w / w" or "% wt / wt" refer to a percentage expressed in terms of the weight of an ingredient or agent divided by the total weight of the composition and multiplied by 100.

[0080] Exemplary anti-Gal3 antibody and its conjugate fragment In some embodiments, an antibody or a binding fragment thereof is provided. In some embodiments, the antibody is an anti-Gal3 antibody or a binding fragment thereof. In some embodiments, the anti-Gal3 antibody or a binding fragment thereof comprises a light chain variable region comprising V L -CDR1, V L -CDR2, and V L -CDR3. In some embodiments, the anti-Gal3 antibody or a binding fragment thereof comprises a heavy chain variable region comprising V H -CDR1, V H -CDR2, and V H -CDR3. In some embodiments, V L -CDR1 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any of the amino acid sequences set forth in SEQ ID NOs: 170-220. In some embodiments, V L -CDR2 comprises an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to any of the amino acid sequences set forth in SEQ ID NOs: 221-247. In some embodiments, V L-CDR3 contains 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 with any of the amino acid sequences described in SEQ ID NOs. H -CDR1 contains 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 with any of the amino acid sequences described in SEQ ID NOs. H -CDR2 contains 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 with any of the amino acid sequences described in SEQ ID NOs: 71-111, 826. H-CDR3 contains 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 of the amino acid sequences described in SEQ ID NOs: 112-169, 827. L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, V H -CDR3 (one or more of these CDRs) It contains one or more sequences that have 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 with respect to a set (containing 2, 3, 4, or 5 amino acid substitutions).

[0081] In some embodiments, an antibody or its conjugated fragment is provided. In some embodiments, the antibody or its conjugated fragment is an anti-Gal3 antibody or its conjugated fragment. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V L -CDR1, V L -CDR2, and V L -Contains a light chain variable region including CDR3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V H -CDR1, V H -CDR2, and V H -Includes a heavy chain variable region including CDR3. In some embodiments, V L-CDR1 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to any of the amino acid sequences described in SEQ ID NOs. L -CDR2 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to any of the amino acid sequences described in SEQ ID NOs. L -CDR3 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to any of the amino acid sequences described in SEQ ID NOs. H-CDR1 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to any of the amino acid sequences described in SEQ ID NOs. H -CDR2 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to any of the amino acid sequences described in SEQ ID NOs. H -CDR3 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to any of the amino acid sequences described in SEQ ID NOs: 112-169, 827. L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, V H -CDR3 (These CDRs The set includes one or more sequences that have at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similarity to any one or more sets (containing 1, 2, 3, 4, or 5 amino acid substitutions).

[0082] In some embodiments, an antibody or its conjugated fragment is provided. In some embodiments, the antibody or its conjugated fragment is an anti-Gal3 antibody or its conjugated fragment. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V L -CDR1, V L -CDR2, and V L -Contains a light chain variable region including CDR3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V H -CDR1, V H -CDR2, and V H -Includes a heavy chain variable region including CDR3. In some embodiments, V L -CDR1 includes an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to any of the amino acid sequences described in SEQ ID NOs. 170-220. In some embodiments, V L -CDR2 includes an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to any of the amino acid sequences described in SEQ ID NOs. 221-247. In some embodiments, V L -CDR3 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to any of the amino acid sequences described in SEQ ID NOs. 248-296. In some embodiments, V H -CDR1 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to any of the amino acid sequences described in SEQ ID NOs. 27-70. In some embodiments, V H-CDR2 includes an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to any of the amino acid sequences described in SEQ ID NOs. 71-111, 826. In some embodiments, V H -CDR3 includes an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to any of the amino acid sequences described in SEQ ID NOs. 112-169, 827.

[0083] In some embodiments, the antibody or its binding fragment is shown in Figure 14. L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, and V H -Includes CDR3 combinations.

[0084] In some embodiments, the antibody or its bound fragment is V L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, and V H - A combination of CDR3, in which one or more of these CDRs are defined by a consensus sequence. The consensus sequences provided herein are derived from the alignment of CDRs as depicted in Figures 33A-B. However, alternative alignments (e.g., using global or local alignments, or using different algorithms, such as hidden Markov models, seeded guide trees, Needleman-Wunsch algorithms, or Smith-Waterman algorithms) may be performed, and it is assumed that alternative consensus sequences may be derived as a result.

[0085] In some embodiments, V L -CDR1 is the formula X1X2X3X4X5X6X7X8X9X 10 X 11 X12 X 13 X 14 X 15 X 16 X 17 Defined by, where X1 is no amino acid or R; X2 is no amino acid or S; X3 is no amino acid, S, or T; X4 is no amino acid, E, G, K, Q, or R; X5 is no amino acid, A, D, G, I, N, or S; X6 is no amino acid, I, L, or V; X7 is no amino acid, F, L, S, or V; X8 is no amino acid, D, E, H, N, S, T, or Y; X9 is no amino acid, D, E, I, K, N, R, S, T, or V; X 10 It is an amino acid without D, H, N, R, S, or Y; X 11 It is an amino acid, or A, G, N, S, T, or V; X 12 is amino Acid-free, A, I, K, N, Q, T, V, or Y; X 13 It is no amino acid, D, G, H, K, N, S, T, or Y; X 14 It is no amino acid, C, F, I, N, S, T, V, or Y; X 15 It is no amino acid, D, L, N, W, or Y; X 16 It is no amino acid, N, or D; X 17 is either amino acid-free or D. In some embodiments, V L -CDR1 includes 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 with respect to this consensus sequence. In some embodiments, V L -CDR1 contains a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0086] In some embodiments, V L-CDR2 is defined by the formula X1X2X3X4X5X6X7X8, where X1 is no amino acid, K, L, N, Q, or R; X2 is no amino acid, A, L, M, or V; X3 is no amino acid, C, K, or S; X4 is no amino acid or T; X5 is no amino acid, A, E, F, G, H, K, Q, R, S, W, or Y; X6 is no amino acid, A, G, or T; X7 is no amino acid, I, K, N, S, or T; X8 is no amino acid, N, or S. In some embodiments, V L -CDR2 includes 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 with respect to this consensus sequence. In some embodiments, V L -CDR2 contains a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0087] In some embodiments, V L -CDR3 is the formula X1X2X3X4X5X6X7X8X9X 10 Defined by, where X1 is no amino acid, A, E, F, H, L, M, Q, S, V, or W; X2 is A, H, or Q; X3 is D, F, G, H, L, M, N, Q, S, T, W, or Y; X4 is no amino acid or W; X5 is A, D, I, K, L, N, Q, R, S, T, V, or Y; X6 is D, E, H, I, K, L, N, Q, S, or T; X7 is D, F, K, L, N, P, S, T, V, W, or Y; X8 is H, P, or S; X9 is F, L, P, Q, R, T, W, or Y; X 10 is amino acid-free, T, or V. In some embodiments, V L-CDR3 includes 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 this consensus sequence. In some embodiments, V L -CDR3 includes sequences having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0088] In some embodiments, V H -CDR1 is defined by the formula X1X2X3X4X5X6X7X8X9X 10 where X1 is E, G, or R; X2 is F, N, or Y; X3 is A, I, K, N, S, or T; X4 is F, I, or L; X5 is I, K, N, R, S, or T; X6 is D, G, I, N, S, or T; X7 is F, G, H, S, or Y; X8 is no amino acid, A, D, G, I, M, N, T, V, W, or Y; X9 is no amino acid, M, or Y; X 10 is no amino acid or G; In some embodiments, V H -CDR1 includes 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 this consensus sequence. In some embodiments, V H -CDR1 includes sequences having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0089] In some embodiments, V H -CDR2 is defined by the formula X1X2X3X4X5X6X7X8X9X 10defined by, where X1 is no amino acid, I, or L; X2 is no amino acid or R; X3 is no amino acid, F, I, L, or V; X4 is A, D, F, H, K, L, N, S, W, or Y; X5 is A, D, P, S, T, W, or Y; X6 is D, E, G, H, K, N, S, V, or Y; X7 is D, E, G, N, S, or T; X8 is D, G, I, K, N, Q, R, S, V, or Y; X9 is A, D, E, G, I, K, N, P, S, T, V, or Y; X 10 is no amino acid, I, P, S, or T. In some embodiments, V H -CDR2 comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to this consensus sequence. In some embodiments, V H -CDR2 comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0090] In some embodiments, V H -CDR3 has the formula X1X2X3X4X5X6X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 X 17 X 18 X 19 X 20 X 21 X 22 X 23 X 24 X 25Defined by, where X1 is no amino acid or is A; X2 is no amino acid, A, R, or Y; X3 is no amino acid, A, F, H, K, L, R, S, or V; X4 is no amino acid, A, D, K, N, R, S, or T; X5 is no amino acid, A, D, G, H, I, L, N, P, R, S, T, V, or Y; X6 is no amino acid, A, D, G, H, K, N, P, Q, R, S, or Y; X7 is no amino acid, D, F, G, H, P, R, S, W, or Y; X8 is no amino acid, A, D, E, G, I, R, or S; X9 is no amino acid, A, C, D, E, F, G, I, N, R, S, T, V, or Y; X 10 It is an amino acid without any, A, D, M, P, R, S, T, V, or Y; X 11 It is an amino acid without any, A, D, E, F, L, T, V, or Y; X 12 It is an amino acid without any, A, G, L, M, R, or T; X 13 It is an amino acid without any, A, D, E, F, G, R, S, T, or V; X 14 It is an amino acid without any, A, D, G, L, P, Q, R, S, T, V, or Y; X 15 It is an amino acid, or A, D, G, N, S, V, W, or Y; X 16 It is an amino acid without any, A, D, E, F, L, P, T, V, W, or Y; X 17 It is no amino acid, F, I, L, M, R, or Y; X 18 It is an amino acid without any, A, D, G, N, or T; X 19 It is no amino acid, F, N, S, T, V, or Y; X 20 is without amino acids or L; X 21 is without amino acids or is A; X 22 is without amino acids or is W; X 23 is without amino acids or is F;X 24 is without amino acids or is A; X 25 is either amino acid-free or Y. In some embodiments, V H-CDR3 includes 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 with respect to this consensus sequence. In some embodiments, V H -CDR3 contains a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0091] In some embodiments, the light chain variable region of the antibody or its binding fragment contains 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 with a sequence selected from SEQ ID NOs. In some embodiments, the light chain variable region of the anti-Gal3 antibody or its binding fragment contains a sequence selected from SEQ ID NOs. In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or its binding fragment contains at least 80%, 81%, or 82% identity with a sequence selected from SEQ ID NOs. The sequence contains sequences having 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity. In some embodiments, the heavy chain variable region of the antibody or its binding fragment contains sequences selected from SEQ ID NOs. 297-373, 822, and 828. In some embodiments, the antibody or its binding fragment is an anti-Gal3 antibody or its binding fragment.

[0092] In some embodiments, the light chain variable region of the antibody or its binding fragment contains a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% similarity to a sequence selected from SEQ ID NOs: 374-447 and 823-825. In some embodiments, the light chain variable region of the anti-Gal3 antibody or its binding fragment contains a sequence selected from SEQ ID NOs: 374-447 and 823-825. In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or its conjugate fragment contains a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% similarity to a sequence selected from SEQ ID NOs. In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or its conjugate fragment contains a sequence selected from SEQ ID NOs. In some embodiments, the antibody or its conjugate fragment is an anti-Gal3 antibody or its conjugate fragment. In some embodiments, the antibody contains a VL sequence, a VH sequence, a VL / VH pair, and / or V from the heavy chain and light chain sequences depicted in Figure 18. L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, V H - Containing one or more sequences that have 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 with any set of CDR3s (which include one or more 1, 2, 3, 4, or 5 amino acid substitutions in any one of these CDRs).

[0093] In some embodiments, an antibody or its conjugated fragment is provided. In some embodiments, the antibody is an anti-Gal3 antibody or its conjugated fragment. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is VL -CDR1, V L -CDR2, and V L -Contains a light chain variable region including CDR3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V H -CDR1, V H -CDR2, and V H -Includes a heavy chain variable region including CDR3. In some embodiments, V L -CDR1 contains one of the amino acid sequences from sequence numbers 170-220, V L -CDR2 contains one of the amino acid sequences of sequence numbers 211-247, V L -CDR3 contains one of the amino acid sequences of sequence numbers 248-296, V H -CDR1 contains one of the amino acid sequences from sequence numbers 27-70, V H -CDR2 contains one of the amino acid sequences of sequence numbers 71-111, 826, and V H -CDR3 contains one of the amino acid sequences of SEQ ID NOs. 112-169, 827, and the light chain variable region contains at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 10% of one of the amino acid sequences of SEQ ID NOs. 374-447, 823-825. The sequence has 0% identity, and the heavy chain variable region has a sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one of the amino acid sequences of sequence numbers 297-373, 822, and 828.

[0094] In some embodiments, the antibody or its conjugated fragment comprises a light chain having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with a sequence selected from SEQ ID NOs. 495-538, 830. This includes. In some embodiments, the light chain includes a sequence selected from SEQ ID NOs: 495-538, 830. In some embodiments, the anti-Gal3 antibody or its conjugate fragment includes a heavy chain, the heavy chain includes 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 with a sequence selected from SEQ ID NOs: 448-494, 829. In some embodiments, the antibody or its conjugate fragment is an anti-Gal3 antibody or its conjugate fragment.

[0095] In some embodiments, the antibody or its conjugated fragment comprises a light chain, the light chain comprising a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% similarity to a sequence selected from SEQ ID NOs. In some embodiments, the anti-Gal3 antibody or its conjugated fragment comprises a heavy chain, the heavy chain containing a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% similarity to a sequence selected from SEQ ID NOs. In some embodiments, the heavy chain contains a sequence selected from SEQ ID NOs. In some embodiments, the antibody or its conjugated fragment is an anti-Gal3 antibody or its conjugated fragment.

[0096] In some embodiments, an antibody or its conjugated fragment is provided. In some embodiments, the antibody is an anti-Gal3 antibody or its conjugated fragment. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V L -CDR1, V L -CDR2, and V L-Contains a light chain variable region including CDR3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V H -CDR1, V H -CDR2, and V H -Includes a heavy chain variable region including CDR3. In some embodiments, V L -CDR1 contains one of the amino acid sequences from sequence numbers 170-220, V L -CDR2 contains one of the amino acid sequences of sequence numbers 211-247, V L -CDR3 contains one of the amino acid sequences of sequence numbers 248-296, V H -CDR1 contains one of the amino acid sequences from sequence numbers 27-70, V H -CDR2 contains one of the amino acid sequences of sequence numbers 71-111, 826, and V H -CDR3 contains one of the amino acid sequences of SEQ ID NOs. 112-169, 827, and the light chain contains at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 10% of one of the amino acid sequences of SEQ ID NOs. 495-538, 830. The sequence has 0% identity, and the heavy chain has a sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to one of the amino acid sequences of sequence numbers 448-494 and 829.

[0097] In some embodiments, an antibody or a conjugated fragment thereof is provided. In some embodiments, the antibody is an anti-Gal3 antibody or a conjugated fragment thereof. In some embodiments, the anti-Gal3 antibody or a conjugated fragment thereof includes a light chain variable region and a heavy chain variable region. In some embodiments, the light chain variable region is paired with an IgG4 kappa chain constant domain. In some embodiments, the IgG4 kappa chain constant domain includes 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 with SEQ ID NO: 833. In some embodiments, the heavy chain variable region is paired with an IgG4 heavy chain constant domain or an IgG2 heavy chain constant domain. Some embodiments In this embodiment, the IgG4 heavy chain constant domain or the IgG2 heavy chain constant domain is human or mouse. In some embodiments, the IgG4 heavy chain constant domain contains 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: 832. In some embodiments, the IgG4 heavy chain constant domain is the S228P mutant. In some embodiments, the IgG2 heavy chain constant domain includes 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 with SEQ ID NO: 838 or SEQ ID NO: 839. In some embodiments, the IgG2 heavy chain constant domain is LALAPG or a LALA mutant. In some embodiments, the light chain variable region and / or heavy chain variable region may be selected from those depicted in Figures 15 and 16 and / or combinations of light chain variable regions and heavy chain variable regions depicted in Figure 17. In some embodiments, the light chain variable region and / or heavy chain variable region includes one or more CDRs depicted in Figures 8-13 and / or combinations of CDRs depicted in Figure 14.

[0098] In some embodiments, the antibody or its conjugated fragment is 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, 13G 4.2F8, 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, 847.28 Selected from D1, 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, or the group consisting of these binding fragments.

[0099] In some embodiments, the antibody or its conjugated fragment is 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, 9 H2.2H10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F84 6C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F 847C.26F5, F847C.4B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846T.1H2, 8 47.14H4, 846.2D4, 846.2F11, 846T.10B1, 846T.2E3, 846T.4C9, 846T.4E11, 846T.4 F5, 846T.8D1, 847.10C9, 847.11D6, 847.15D12, 847.15F9, 847.15H11, 847.20H7, 8 47.21B11, 847.27B9, 847.28D1, 847.2B8, 847.3B3, 849.1D2, 849.2D7, 849.2F12, 84 9.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12, F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847.4D3, or 2D10-VH0 - Contains 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 with respect to the VL0 sequence.

[0100] In some embodiments, the antibody or its conjugated fragment is 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, 19D 9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F 846C.1H5, F846C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846T C.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4B 10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 846T.1H2, 847.14H4, 8 46.2D4, 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, 849.1D 2, 849.2D7, 849.2F12, 849.4B2, 849.4F12, 849.4F2, 849.5C2, 849.8D12 The sequence includes sequences (e.g., CDR, VL, VH, LC, HC) having at least 80%, 81%, 82%, 83%, 844%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to the sequences F847C.21H6, 849.5H1, 847.23F11, 847.16D10, 847.13E2-mH0mL1, 847.13E2-mH0mL2, 847.12C4, 847.4D3, or 2D10-VH0-VL0.

[0101] In some embodiments, an antibody or its conjugated fragment is provided. In some embodiments, the antibody or its conjugated fragment is an anti-Gal3 antibody or its conjugated fragment. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V L -CDR1, V L -CDR2, and V L -Contains a light chain variable region including CDR3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V H -CDR1, V H -CDR2, and V H -Includes a heavy chain variable region including CDR3. In some embodiments, V L -CDR1 is at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% for SEQ ID NO: 170 It contains an amino acid sequence having %, 98%, 99%, or 100% sequence identity. In some embodiments, V L -CDR2 contains 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 with respect to SEQ ID NO: 221. L-CDR3 contains 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 with respect to SEQ ID NO: 248. H -CDR1 contains 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 with respect to SEQ ID NO: 27. H -CDR2 contains 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 with respect to SEQ ID NO: 71. H -CDR3 contains 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 with respect to SEQ ID NO: 112.

[0102] In some embodiments, an antibody or its conjugated fragment is provided. In some embodiments, the antibody or its conjugated fragment is an anti-Gal3 antibody or its conjugated fragment. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V L -CDR1, V L -CDR2, and V L -Contains a light chain variable region including CDR3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V H -CDR1, V H -CDR2, and V H -Includes a heavy chain variable region including CDR3. In some embodiments, V L -CDR1 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 170. L -CDR2 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 221. L -CDR3 is at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85% for Array No. 248. The amino acid sequences include those having sequence similarity of %, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%. In some embodiments, V H -CDR1 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 27. H -CDR2 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 71. H -CDR3 contains an amino acid sequence having at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence similarity to SEQ ID NO: 112.

[0103] In some embodiments, an antibody or its conjugated fragment is provided. In some embodiments, the antibody or its conjugated fragment is an anti-Gal3 antibody or its conjugated fragment. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V L -CDR1, V L -CDR2, and V L-Contains a light chain variable region including CDR3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is V H -CDR1, V H -CDR2, and V H -Includes a heavy chain variable region including CDR3. In some embodiments, V L -CDR1 contains an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to SEQ ID NO: 170. In some embodiments, V L -CDR2 contains an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to SEQ ID NO: 221. In some embodiments, V L -CDR3 comprises an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to SEQ ID NO: 248. In some embodiments, V H -CDR1 contains an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to SEQ ID NO: 27. In some embodiments, V H -CDR2 contains an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to SEQ ID NO: 71. In some embodiments, V H -CDR3 contains an amino acid sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to SEQ ID NO: 112.

[0104] In some embodiments, the light chain variable region of the anti-Gal3 antibody or its binding fragment contains 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 with SEQ ID NO: 374. In some embodiments, the light chain variable region of the anti-Gal3 antibody or its binding fragment contains the sequence of SEQ ID NO: 374. In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or its binding fragment contains 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 with SEQ ID NO: 297. In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or its binding fragment contains the sequence of SEQ ID NO: 297.

[0105] In some embodiments, the light chain variable region of the anti-Gal3 antibody or its binding fragment is at least 80%, 81%, 82%, 83%, 84%, 85%, and 86% relative to SEQ ID NO: 374. The sequence includes sequences having 80%, 81%, 82%, 83%, 84%, 85%, 96%, 97%, 98%, or 99% similarity. In some embodiments, the light chain variable region of the anti-Gal3 antibody or its binding fragment includes the sequence of SEQ ID NO: 374. In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or its binding fragment includes sequences having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% similarity to the sequence of SEQ ID NO: 297. In some embodiments, the heavy chain variable region of the anti-Gal3 antibody or its binding fragment includes the sequence of SEQ ID NO: 297.

[0106] In some embodiments, the anti-Gal3 antibody or its conjugated fragment comprises a light chain, the light chain comprising a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence of SEQ ID NO: 495. In some embodiments, the light chain comprises the sequence of SEQ ID NO: 495. In some embodiments, the anti-Gal3 antibody or its conjugated fragment comprises a heavy chain, the heavy chain comprising a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the sequence of SEQ ID NO: 448. In some embodiments, the heavy chain includes the sequence of SEQ ID NO: 448.

[0107] In some embodiments, the anti-Gal3 antibody or its conjugated fragment comprises a light chain, the light chain comprising a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% similarity to the sequence of SEQ ID NO: 495. In some embodiments, the light chain comprises the sequence of SEQ ID NO: 495. In some embodiments, the anti-Gal3 antibody or its conjugated fragment comprises a heavy chain, the heavy chain comprising a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% similarity to the sequence of SEQ ID NO: 448. In some embodiments, the heavy chain includes the sequence of SEQ ID NO: 448.

[0108] In some embodiments, the anti-Gal3 antibody or its conjugated fragment binds to a specific epitope within the Gal3 protein. In some embodiments, the anti-Gal3 antibody or its conjugated fragment binds to a specific epitope within the Gal3 protein having the amino acid sequence described in SEQ ID NOs: 1-2, provided in Figure 6.

[0109] In some embodiments, the anti-Gal3 antibody or its binding fragment may be bound 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 in the peptides shown in Figure 7 (SEQ ID NOs: 3-26).

[0110] In some embodiments, the anti-Gal3 antibody or its conjugated fragment may be bound 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 NOs: 1-2. In some embodiments, the anti-Gal3 antibody or its conjugated fragment may be bound 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 NOs: 1-2. In some embodiments, the anti-Gal3 antibody or its conjugated fragment may be bound to at least 1, 2, 3, 4, 5, 6, within amino acid residues 51-70 of SEQ ID NOs: 1-2. It may bind to 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues. In some embodiments, the anti-Gal3 antibody or its binding fragment 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 NOs.

[0111] In some embodiments, the anti-Gal3 antibody or its conjugated fragment may be bound 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 in peptide 1 (sequence number 3), peptide 4 (sequence number 6), peptide 6 (sequence number 8), or peptide 7 (sequence number 9). In some embodiments, the anti-Gal3 antibody or its conjugated fragment may be bound 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 in peptide 1 (sequence number 3). In some embodiments, the anti-Gal3 antibody or its conjugated fragment may be bound to at least 11, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid residues in peptide 4 (SEQ ID NO: 6). In some embodiments, the anti-Gal3 antibody or its conjugated fragment may be bound 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 in peptide 6 (SEQ ID NO: 8). In some embodiments, the anti-Gal3 antibody or its conjugated fragment may be bound 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 in peptide 7 (SEQ ID NO: 9). In some embodiments, the anti-Gal3 antibody or its conjugated fragment binds to an epitope located within the Gal3 region defined by peptide 1 (sequence number 3). In some embodiments, the anti-Gal3 antibody or its conjugated fragment binds to an epitope located within the Gal3 region defined by peptide 4 (sequence number 6). In some embodiments, the anti-Gal3 antibody or its conjugated fragment binds to an epitope located within the Gal3 region defined by peptide 6 (sequence number 8). In some embodiments, the anti-Gal3 antibody or its conjugated fragment binds to an epitope located within the Gal3 region defined by peptide 7 (sequence number 9). In some embodiments, the antibody binds to one, two, or all three of peptides 1, 6, and / or 7.

[0112] In some embodiments, the anti-Gal3 antibody or its conjugate fragment described herein may be bound to the N-terminal domain or portion thereof of Gal3. In some embodiments, the anti-Gal3 antibody or its conjugate fragment described herein may be bound to an epitope of Gal3 comprising a GxYPG motif, where x is the amino acid alanine (A), glycine (G), or valine (V). In some embodiments, the anti-Gal3 antibody or its conjugate fragment described herein may be bound to an epitope of Gal3 comprising two GxYPG motifs separated by three amino acids, where x is A, G, or V.

[0113] In some embodiments, the anti-Gal3 antibody or its conjugate fragment binds to Gal3. In some embodiments, the anti-Gal3 antibody or its conjugate fragment binds to the N-terminus of Gal3, the N-terminal domain of Gal3, or the TRD of Gal3. In some embodiments, the anti-Gal3 antibody or its conjugate fragment does not bind to the N-terminus of Gal3, the N-terminal domain of Gal3, or the TRD of Gal3. In some embodiments, the anti-Gal3 antibody or its conjugate fragment binds to the C-terminus of Gal3, the C-terminal domain of Gal3, or the CRD of Gal3. In some embodiments, the anti-Gal3 antibody or its conjugate fragment binds to Gal3. 3. Binds to isoform 1. In some embodiments, the anti-Gal3 antibody or its binding fragment binds to the N-terminus of Gal3 isoform 1, the N-terminal domain of Gal3 isoform 1, amino acids 1-111 of Gal3 isoform 1, the TRD of Gal3 isoform 1, or amino acids 36-109 of Gal3 isoform 1. In some embodiments, the anti-Gal3 antibody or its binding fragment does not bind to the N-terminus of Gal3 isoform 1, the N-terminal domain of Gal3 isoform 1, amino acids 1-111 of Gal3, the TRD of Gal3 isoform 1, or amino acids 36-109 of Gal3 isoform 1. In some embodiments, the anti-Gal3 antibody or its binding fragment binds to the C-terminus of Gal3 isoform 1, the C-terminal domain of Gal3 isoform 1, amino acids 112-250 of Gal3, or the CRD of Gal3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment does not bind to the C-terminus of Gal3 isoform 1, the C-terminal domain of Gal3 isoform 1, amino acids 112-250 of Gal3 isoform 1, or the CRD of Gal3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment binds to the N-terminus of Gal3 isoform 3, the N-terminal domain of Gal3 isoform 3, amino acids 1-125 of Gal3, the TRD of Gal3 isoform 3, or amino acids 50-123 of Gal3 isoform 3. In some embodiments, the anti-Gal3 antibody or its conjugated fragment does not bind to the N-terminus of Gal3 isoform 3, the N-terminal domain of Gal3 isoform 3, amino acids 1-125 of Gal3 isoform 3, the TRD of Gal3, or amino acids 50-123 of Gal3 isoform 3. In some embodiments, the anti-Gal3 antibody or its binding fragment binds to the C-terminus of Gal3 isoform 3, the C-terminal domain of Gal3 isoform 3, amino acids 126-264 of Gal3 isoform 3, or the CRD of Gal3.In some embodiments, the anti-Gal3 antibody or its binding fragment does not bind to the C-terminus of Gal3 isoform 3, the C-terminal domain of Gal3 isoform 3, amino acids 126-264 of Gal3 isoform 3, or the CRD of Gal3 isoform 3.

[0114] In some embodiments, the interaction between Gal3 and cell surface markers can be reduced to less than 80%, less than 75%, less than 70%, less than 60%, less than 59%, less than 50%, less than 40%, less than 34%, less than 30%, less than 20%, less than 14%, less than 10%, less than 7%, less than 5%, less than 4%, or less than 1%.

[0115] In some embodiments, the interaction between Gal3 and viral proteins (e.g., SARS-CoV-2 S, E, M, or HE proteins) can be reduced to less than 80%, less than 75%, less than 70%, less than 60%, less than 59%, less than 50%, less than 40%, less than 34%, less than 30%, less than 20%, less than 14%, less than 10%, less than 7%, less than 5%, less than 4%, or less than 1%. In some embodiments, the interaction between Gal3 and host receptor proteins (e.g., ACE2 or CD147) can be reduced to less than 80%, less than 75%, less than 70%, less than 60%, less than 59%, less than 50%, less than 40%, less than 34%, less than 30%, less than 20%, less than 14%, less than 10%, less than 7%, less than 5%, less than 4%, or less than 1%.

[0116] In some embodiments, the anti-Gal3 antibody or its binding fragment has a dissociation constant (K) of less than 1 nM, less than 1.2 nM, less than 2 nM, less than 5 nM, less than 10 nM, less than 13.5 nM, less than 15 nM, less than 20 nM, less than 25 nM, or less than 30 nM. D ) binds to Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment is less than 1 nM K D It binds to Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment is less than 1.2 nM K DIt binds to Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment is less than 2 nM K D It binds to Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment is less than 5 nM K D Then combine with Gal3 In some embodiments, the anti-Gal3 antibody or its conjugated fragment is less than 10 nM K D It binds to Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment is less than 13.5 nM of K. D It binds to Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment is less than 15 nM K D It binds to Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment is less than 20 nM K D It binds to Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment is less than 25 nM K D It binds to Gal3. In some embodiments, the anti-Gal3 antibody or its binding fragment is less than 30 nM K D Then it is combined with Gal3.

[0117] In some embodiments, the anti-Gal3 antibody or its binding fragment is located in the variable heavy chain complementarity determination region 1(V) shown in Figure 8. H -CDR1) contains one of the sequences (SEQ ID NOs. 27-70). In some embodiments, the anti-Gal3 antibody has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to one of SEQ ID NOs. 27-70. H-Contains the CDR1 sequence. In some embodiments, the anti-Gal3 antibody has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs. 27-70. H -Includes the CDR1 sequence.

[0118] In some embodiments, the anti-Gal3 antibody or its binding fragment is located in the variable heavy chain complementarity determination region 2(V) shown in Figure 9. H -CDR2) contains one of the sequences (SEQ ID NOs. 71-111, 826). In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to one of SEQ ID NOs. 71-111, 826. H -Contains a CDR2 sequence. In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs. 71-111, 826. H -Includes CDR2 sequence

[0119] In some embodiments, the anti-Gal3 antibody or its binding fragment is located in the variable heavy chain complementarity determination region 3(V) shown in Figure 10. H -CDR3) sequence (SEQ ID NOs. 112-169, 827) is included in any one of these. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or V with at least 99% sequence identity H -Contains a CDR3 sequence. In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs. 112-169, 827. H -Includes the CDR3 sequence.

[0120] In some embodiments, the anti-Gal3 antibody or its binding fragment is located in the variable light chain complementarity determination region 1(V) shown in Figure 11. L-CDR1) contains one of the sequences (SEQ ID NOs. 170-220). In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to one of SEQ ID NOs. 170-220. L -Contains the CDR1 sequence. In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs. 170-220. L -Includes the CDR1 sequence.

[0121] In some embodiments, the anti-Gal3 antibody or its binding fragment is located in the variable light chain complementarity determination region 2(V) shown in Figure 12. L -CDR2) contains one of the sequences (SEQ ID NOs. 221-247). In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to one of SEQ ID NOs. 221-247. L-Contains the CDR2 sequence. In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs. 221-247. L -Includes CDR2 sequence

[0122] In some embodiments, the anti-Gal3 antibody or its binding fragment is located in the variable light chain complementarity determination region 3(V) shown in Figure 13. L -CDR3) contains one of the sequences (SEQ ID NOs. 248-296). In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to one of SEQ ID NOs. 248-296. L -Contains a CDR3 sequence. In some embodiments, anti-Gal3 The antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs. 248-296. L -Includes the CDR3 sequence.

[0123] In some embodiments, the anti-Gal3 antibody or its binding fragment is a heavy chain variable region (V H ) and light chain variable region (V L ) includes. In some embodiments, V H V is selected from any of Figures 8-10. H -CDR1, V H -CDR2, and / or V H -CDR3 may be included in some embodiments. L V is selected from any of Figures 11-13. L -CDR1, V L -CDR2, and / or V L -CDR3 may be included. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is shown in Figure 14. H and V L Includes CDR within the sequence. It is understood that antibodies having the antibody names described herein may be referred to using the abbreviated version of the antibody name, provided that there is no conflict with another antibody described herein. For example, F846C.1B2 may also be referred to as 846C.1B2, or 846.1B2.

[0124] In some embodiments, the anti-Gal3 antibody or its binding fragment is a heavy chain variable region (V) selected from Figure 15. H ) containing sequences (SEQ ID NOs. 297-373, 822, 828). In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to any one of SEQ ID NOs. 297-373, 822, 828. HIncludes a sequence. In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs. 297-373, 822, or 828. H Includes arrays.

[0125] In some embodiments, the anti-Gal3 antibody or its binding fragment is a light chain variable region (V) selected from Figure 16. L ) containing sequences (SEQ ID NOs. 374-447, 823-825). In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with any one of SEQ ID NOs. 374-447, 823-825. L Includes a sequence. In some embodiments, the anti-Gal3 antibody or its conjugated fragment has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence similarity to any one of SEQ ID NOs. 374-447, 823-825. L Includes arrays.

[0126] In some embodiments, the anti-Gal3 antibody or its binding fragment includes a combination of heavy chain variable regions and light chain variable regions as shown in Figure 17.

[0127] In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes the heavy and light chain sequences shown in Figure 18 (SEQ ID NOs: 448-538, 830).

[0128] In some embodiments, the anti-Gal3 antibody or its conjugated fragment is 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, 9H2.2H1 0, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F846 C.2H3, F846TC.14A2, F846TC.14E4, F846TC.16B5, F846TC.7F10, F847C.10B9, F847C.11B1, F847C.12F12, F847C.26F5, F847C.4 B10, F849C.8D10, F849C.8H3, 846.2B11, 846.4D5, 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, or a selection from the group of these binding fragments.

[0129] In some embodiments, the anti-Gal3 antibody or its conjugated fragment is 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, 9H2.2H 10, 13G4.2F8, 13H12.2F8, 15G7.2A7, 19D9.2E5, 23B10.2B12, 24D12.2H9, F846C.1B2, F846C.1F5, F846C.1H12, F846C.1H5, F84 6C.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.4C 9, 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, or containing these binding fragments. Essentially, it becomes or consists of.

[0130] In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes one or more heavy chain variable regions (CDRs) as depicted in Figures 8-10. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes one or more light chain variable regions (CDRs) as depicted in Figures 11-13. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a heavy chain variable region as depicted in Figure 15. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a light chain variable region as depicted in Figure 16. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a combination of a heavy chain variable region and a light chain variable region as depicted in Figure 17. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a heavy chain and / or light chain as depicted in Figure 18. In some embodiments, the anti-Gal3 antibody or its conjugated fragment may contain or include one or more sequences provided in one or more of Figures 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18, or one or more sequences with at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity. In some embodiments, the anti-Gal3 antibody or its conjugated fragment may include or encompass one or more sequences provided in one or more of Figures 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18, or one or more sequences of at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher similarity.

[0131] In some embodiments, the anti-Gal3 antibody or its conjugate fragment comprises a humanized antibody or its conjugate fragment. In other embodiments, the anti-Gal3 antibody or its conjugate fragment comprises a chimeric antibody or its conjugate fragment. In some embodiments, the anti-Gal3 antibody comprises a full-length antibody or its conjugate fragment. In some embodiments, the anti-Gal3 antibody or its conjugate fragment comprises a bispecific antibody or its conjugate fragment. In some embodiments, the anti-Gal3 antibody or its conjugate fragment comprises a monovalent Fab', a bivalent Fab2, a single-chain variable fragment (scFv), a diabody, a minibody, a nanobody, a single-domain antibody (sdAb), or a camelid antibody or its conjugate fragment.

[0132] In some embodiments, the anti-Gal3 antibody or its conjugated fragment is a bispecific antibody or its conjugated fragment. Exemplary bispecific antibody formats include, but are not limited to, knob-into-hole (KiH), asymmetric re-engineering technology-immunoglobulin (ART-Ig), triomab quadroma, bispecific monoclonal antibodies (BiMAb, BsmAb, BsAb, bsMab, BS-Mab, or Bi-MAb), azymetric, biclonics, Fab-scFv-Fc, Two-in-one / Dual Action Fab (DAF), FinomAb, scFv-Fc-(Fab) fusion, Dock-aNd-Lock (DNL), Tandem diAbody (TandAb), Dual-affinity-ReTargeting (DART), nanobody, triplebody, tandem scFv (taFv), triplehead, tandem dAb / VHH, triple dAb / VHH, or tetravalent dAb / VHH. In some embodiments, the anti-Gal3 antibody or its conjugated fragment is a bispecific antibody or its conjugated fragment, comprising the bispecific antibody format shown in FIG. 2 of Non-Patent Document 21.

[0133] In some embodiments, the anti-Gal3 antibody or its binding fragment is IgM, IgG (e.g.) For example, it may include an IgG1, IgG2, IgG3, or IgG4, IgA, or IgE framework. The IgG framework can be IgG1, IgG2, IgG3, or IgG4. In some embodiments, the anti-Gal3 antibody or its conjugate fragment includes an IgG1 framework. In some embodiments, the anti-Gal3 antibody or its conjugate fragment includes an IgG2 framework. In some embodiments, the anti-Gal3 antibody or its conjugate fragment includes an IgG4 framework. The anti-Gal3 antibody or its conjugate fragment may further include an Fc mutation.

[0134] In some embodiments, the Fc region includes one or more mutations that modulate Fc receptor interactions, for example, to enhance effector function, such as ADCC and / or CDC. In such cases, exemplary residues that modulate effector function when mutated include S239, K326, A330, I332, or E333, where the residue positions correspond to IgG1 and the residue numbering is according to Kabat numbering (EU index in Non-Patent Literature 2) (Figure 19). In some embodiments, one or more mutations include S239D, K326W, A330L, I332E, E333A, E333S, or combinations thereof. In some embodiments, one or more mutations include S239D, I332E, or combinations thereof. In some embodiments, one or more mutations include S239D, A330L, I332E, or combinations thereof. In some embodiments, one or more mutations include K326W, E333S, or a combination thereof. In some embodiments, the mutation includes E333A.

[0135] In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a humanization score higher than 70, higher than 80, higher than 81, higher than 82, higher than 83, higher than 84, higher than 85, higher than 86, higher than 87, higher than 88, higher than 89, higher than 90, or higher than 95. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a humanization score higher than 80. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a humanization score higher than 83. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a humanization score higher than 85. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a humanization score higher than 87. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a humanization score higher than 90. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a humanization score for the heavy chain higher than 70, higher than 80, higher than 81, higher than 82, higher than 83, higher than 84, higher than 85, higher than 86, higher than 87, higher than 88, higher than 89, higher than 90, or higher than 95, optionally higher than 80, higher than 85, or higher than 87. In some embodiments, the anti-Gal3 antibody or its conjugated fragment includes a humanization score for the light chain higher than 70, higher than 80, higher than 81, higher than 82, higher than 83, higher than 84, higher than 85, higher than 86, higher than 87, higher than 88, higher than 89, higher than 90, or higher than 95, optionally higher than 80, higher than 83, or higher than 85.

[0136] Also disclosed herein are proteins. In some embodiments, a protein comprises one or more of the sequence numbers 170-533. In some embodiments, a protein comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with one or more of the sequence numbers 170-533. In some embodiments, a protein comprises a sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to any one or more of the sequence numbers 170-533. In some embodiments, a protein comprises sequence numbers 170-220; 221-247; 248-296; 27-70; 71 The protein includes six sequences selected from each of the following: ~111, 826; and SEQ ID NOs. 112~169, 827. In some embodiments, the protein includes two sequences selected from each of the following: SEQ ID NOs. 374~447, 823~825 and SEQ ID NOs. 297~373, 822, 828. In some embodiments, the protein includes two sequences selected from each of the following: SEQ ID NOs. 495~538, 830 and SEQ ID NOs. 448~494, 829. In some embodiments, the protein contains one or more sequences selected from the group consisting of SEQ ID NOs: 170-220; SEQ ID NOs: 221-247; SEQ ID NOs: 248-296; SEQ ID NOs: 27-70; SEQ ID NOs: 71-111, 826; SEQ ID NOs: 112-169, 827; SEQ ID NOs: 374-447, 823-825; SEQ ID NOs: 297-373, 822, 828; SEQ ID NOs: 495-538, 830; SEQ ID NOs: 448-494, 829. In some embodiments, the protein contains one or more sequences depicted in Figures 8-18.

[0137] In some embodiments, the protein comprises one or more sequences defined by a consensus sequence. The consensus sequences provided herein are derived from the alignment of the CDRs as depicted in Figures 33A-B. However, alternative alignments (e.g., using global or local alignments, or using different algorithms, such as hidden Markov models, seed-guided trees, Needleman-Wunsch algorithms, or Smith-Waterman algorithms) may be performed, and it is anticipated that alternative consensus sequences may be derived as a result.

[0138] In some embodiments, the protein is expressed by formula X1X2X3X4X5X6X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 X 17 The sequence includes the following, where X1 is no amino acid or R; X2 is no amino acid or S; X3 is no amino acid, S, or T; X4 is no amino acid, E, G, K, Q, or R; X5 is no amino acid, A, D, G, I, N, or S; X6 is no amino acid, I, L, or V; X7 is no amino acid, F, L, S, or V; X8 is no amino acid, D, E, H, N, S, T, or Y; X9 is no amino acid, D, E, I, K, N, R, S, T, or V; X 10 It is an amino acid without D, H, N, R, S, or Y; X 11 It is an amino acid, or A, G, N, S, T, or V; X 12 It is an amino acid without any, A, I, K, N, Q, T, V, or Y; X 13 It is no amino acid, D, G, H, K, N, S, T, or Y; X 14 It is no amino acid, C, F, I, N, S, T, V, or Y; X 15 It is no amino acid, D, L, N, W, or Y; X 16 It is no amino acid, N, or D; X 17This is either amino acid-free or D. In some embodiments, the protein includes 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 with respect to this consensus sequence. In some embodiments, the protein includes a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0139] In some embodiments, the protein comprises a sequence defined by the formula X1X2X3X4X5X6X7X8, where X1 is amino acid-free, K, L, N, Q, or R; X2 is amino acid-free, A, L, M, or V; X3 is amino acid-free, C, K, or S; X4 is amino acid-free or T; X5 is amino acid-free, A, E, F, G, H, K, Q, R, S, W, or Y; X6 is amino acid-free, A, G, or T; X7 is amino acid-free, I, K, N, S, or T; X8 is amino acid-free, N, or S. In some embodiments, the protein is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% relative to this consensus sequence. The sequence contains sequences having 98%, 99%, or 100% identity. In some embodiments, the protein contains sequences having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0140] In some embodiments, the protein is expressed by formula X1X2X3X4X5X6X7X8X9X 10The sequence includes the following, where X1 is no amino acid, A, E, F, H, L, M, Q, S, V, or W; X2 is A, H, or Q; X3 is D, F, G, H, L, M, N, Q, S, T, W, or Y; X4 is no amino acid or W; X5 is A, D, I, K, L, N, Q, R, S, T, V, or Y; X6 is D, E, H, I, K, L, N, Q, S, or T; X7 is D, F, K, L, N, P, S, T, V, W, or Y; X8 is H, P, or S; X9 is F, L, P, Q, R, T, W, or Y; X 10 This is amino acid-free, T, or V. In some embodiments, the protein includes 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 with respect to this consensus sequence. In some embodiments, the protein includes a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0141] In some embodiments, the protein is expressed by formula X1X2X3X4X5X6X7X8X9X 10 Includes a sequence defined by, where X1 is E, G, or R; X2 is F, N, or Y; X3 is A, I, K, N, S, or T; X4 is F, I, or L; X5 is I, K, N, R, S, or T; X6 is D, G, I, N, S, or T; X7 is F, G, H, S, or Y; X8 is no amino acid, A, D, G, I, M, N, T, V, W, or Y; X9 is no amino acid, M, or Y; X 10The sequence is either amino acid-free or G; in some embodiments, the protein comprises a sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity with respect to this consensus sequence. In some embodiments, the protein comprises a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0142] In some embodiments, the protein is expressed by formula X1X2X3X4X5X6X7X8X9X 10 The sequence includes the following, where X1 is no amino acid, I, or L; X2 is no amino acid or R; X3 is no amino acid, F, I, L, or V; X4 is A, D, F, H, K, L, N, S, W, or Y; X5 is A, D, P, S, T, W, or Y; X6 is D, E, G, H, K, N, S, V, or Y; X7 is D, E, G, N, S, or T; X8 is D, G, I, K, N, Q, R, S, V, or Y; X9 is A, D, E, G, I, K, N, P, S, T, V, or Y; X 10 This is no amino acid, I, P, S, or T. In some embodiments, the protein includes 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 with respect to this consensus sequence. In some embodiments, the protein includes a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0143] In some embodiments, the protein is expressed by formula X1X2X3X4X5X6X7X8X9X 10 X 11 X 12 X 13 X 14 X 15 X 16 X 17 X 18 X 19 X20 X 21 X 22 X 23 X 24 X 25 Includes a sequence defined by, where X1 is no amino acid or A; X2 is no amino acid, A, R, or Y; X3 is no amino acid, A, F, H, K, L, R, S, or V; X4 is no amino acid, A, D, K, N, R, S, and X5 is T; X5 is no amino acid, A, D, G, H, I, L, N, P, R, S, T, V, or Y; X6 is no amino acid, A, D, G, H, K, N, P, Q, R, S, or Y; X7 is no amino acid, D, F, G, H, P, R, S, W, or Y; X8 is no amino acid, A, D, E, G, I, R, or S; X9 is no amino acid, A, C, D, E, F, G, I, N, R, S, T, V, or Y; X 10 It is an amino acid without any, A, D, M, P, R, S, T, V, or Y; X 11 It is an amino acid without any, A, D, E, F, L, T, V, or Y; X 12 It is an amino acid without any, A, G, L, M, R, or T; X 13 It is an amino acid without any, A, D, E, F, G, R, S, T, or V; X 14 It is an amino acid without any, A, D, G, L, P, Q, R, S, T, V, or Y; X 15 It is an amino acid, or A, D, G, N, S, V, W, or Y; X 16 It is an amino acid without any, A, D, E, F, L, P, T, V, W, or Y; X 17 It is no amino acid, F, I, L, M, R, or Y; X 18 It is an amino acid without any, A, D, G, N, or T; X 19 It is no amino acid, F, N, S, T, V, or Y; X 20 is without amino acids or L; X 21 is without amino acids or is A; X 22 is without amino acids or is W; X 23 is without amino acids or is F;X 24 is without amino acids or is A; X 25This is either amino acid-free or Y. In some embodiments, the protein includes 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 with respect to this consensus sequence. In some embodiments, the protein includes a sequence having 0, 1, 2, 3, 4, 5, or 6 substitutions from this consensus sequence.

[0144] Exemplary pharmaceutical preparations Pharmaceutical formulations for treating the diseases described herein may include the anti-Gal3 antibody or its conjugated fragment. The anti-Gal3 antibody or its conjugated fragment may be formulated for systemic administration. Alternatively, the anti-Gal3 antibody or its conjugated fragment may be formulated for parenteral administration.

[0145] In some embodiments, the anti-Gal3 antibody or its conjugated fragment is formulated as a pharmaceutical composition for administration to a subject via parenteral (e.g., intravenous, subcutaneous, intramuscular, intra-arterial, intradermal, intraperitoneal, intravitreous, intracerebral, or intraventricular), oral, intranasal, buccal, rectal, or transdermal administration routes, but is not limited to the following. In some embodiments, the pharmaceutical compositions described herein are formulated for parenteral (e.g., intravenous, subcutaneous, intramuscular, intra-arterial, intradermal, intraperitoneal, intravitreous, intracerebral, or intraventricular) administration. In other embodiments, the pharmaceutical compositions described herein are formulated for systemic administration. In other embodiments, the pharmaceutical compositions described herein are formulated for oral administration. In yet another embodiment, the pharmaceutical compositions described herein are formulated for intranasal administration.

[0146] In some embodiments, the pharmaceutical composition further comprises acids, such as acetic acid, boric acid, citric acid, lactic acid, phosphoric acid, and hydrochloric acid; bases, such as sodium hydroxide, sodium phosphate, sodium borate, sodium citrate, sodium acetate, sodium lactate, and tris-hydroxymethylaminomethane; and pH adjusters or buffering agents, such as citrate (salt) / dextrose, sodium bicarbonate, and ammonium chloride. Such acids, bases, and buffers are included in amounts required to maintain the pH of the composition within an acceptable range.

[0147] In some embodiments, the pharmaceutical composition contains one or more salts in amounts required to bring the weight osmolality of the composition within an acceptable range. Such salts include those having sodium, potassium, or ammonium cations and chloride, citric acid, ascorbic acid, boric acid, phosphoric acid, bicarbonate, sulfuric acid, thiosulfate, or bisulfite anions; Suitable salts include sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfite, and ammonium sulfate.

[0148] In some embodiments, the pharmaceutical composition further includes a diluent used to stabilize the compound so that a more stable environment can be provided. Salts dissolved in a buffered solution (which can also provide pH control or maintenance) are used as diluents in the art and include, but are not limited to, phosphate-buffered saline solutions. In certain cases, the diluent increases the volume of the composition to facilitate compression or creates a sufficient volume for a homogeneous blend for capsule filling. Such compounds may include, for example, lactose, starch, mannitol, sorbitol, dextrose, microcrystalline cellulose, e.g., Avicel®; dibasic calcium phosphate, dicalcium phosphate dihydrate; tricalcium phosphate, calcium phosphate; anhydrous lactose, spray-dried lactose; pregelatinized starch, compressed sugar, e.g., Di-Pac (Amstar); mannitol, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose stearate acetate, sucrose-based diluents, powdered sugar; monobasic calcium sulfate monohydrate, calcium sulfate dihydrate; calcium lactate trihydrate, dextrose; hydrolyzed cereal solids, amylose; powdered cellulose, calcium carbonate; glycine, kaolin; mannitol, sodium chloride; inositol, and bentonite.

[0149] In some embodiments, pharmaceutical formulations include, but are not limited to, aqueous liquid dispersions, self-emulsifying dispersions, solid solutions, liposome dispersions, aerosols, solid dosing forms, powders, immediate-release formulations, controlled-release formulations, rapid-dissolving formulations, tablets, capsules, pills, delayed-release formulations, sustained-release formulations, pulsatile-release formulations, multi-particle formulations (e.g., nanoparticle formulations), and mixed immediate- and controlled-release formulations.

[0150] In some embodiments, the pharmaceutical formulation may further include additional therapeutic agents. Non-limiting examples of additional therapeutic agents include alpha-glucosidase inhibitors, such as acarbose (Precose) and miglitol (Glyset); metformin-alogliptin (Kazano®), metformin-canagliflozin (Invokamet®), metformin-dapagliflozin (Xigduo® XR), metformin-empagliflozin (Synjardy®), metformin-glipizide, metformin-glibride (Glucovance®), metformin-linagliptin (Jentadueto®), metformin-pioglitazone (Actoplus), metformin-repaglinide (PrandiMet), metformin-rosiglitazone (Avandamet), and metformin-saxagliptin (Kombiglyze®). Biguanides containing XR) and metformin-sitagliptin (Janumet®); dopamine agonists containing bromocriptine (Cycloset®); alogliptin (Nesina®), alogliptin-metformin (Kazano®), alogliptin-pioglitazone (Oseni), linagliptin (Tradjenta), linagliptin-empagliflozin (Glyxambi®), linagliptin-metformin (Jentadueto®), saxagliptin (Onglyza®), saxagliptin-metformin (Kombiglyze® XR), sitagliptin (Januvia®), sitagliptin-metformin (Janumet® and Janumet®) Dipeptidyl peptidase-4 (DPP-4) inhibitors, including XR, sitagliptin, and simvastatin (Juvisync); albiglutide (Tanzeum®), dulaglutide (Trulicity®), exenatide (Byetta®), exenatide sustained-release (Bydureon®), and liraglutide (Victoza®), semaglutide (Ozempic®) Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists), including registered trademarks; meglitinide, including nateglinide (Starlix), repaglinide (Prandin), and repaglinide-metformin (Prandimet); dapagliflozin (Farxiga), dapagliflozin-metformin (Xigduo (registered trademark)) Sodium-glucose transporter (SGLT) 2 inhibitors, including XR), canagliflozin (Invokana®), canagliflozin-metformin (Invokamet®), empagliflozin (Jardiance®), empagliflozin-linagliptin (Glyxambi®), empagliflozin-metformin (Synjardy®), and erzgliflozin (Steglatro); glimepiride (Amaryl®), glimepiride-pioglitazone (Duetact), glimepiride-rosiglitazone (Avand Sulfonylureas including aryl), gliclazide, glipizide (Glucotrol), glipizide-metformin (Metaglip), glybride (DiaBeta®, Glynase, Micronase), glybride-metformin (Glucovance®), chlorpropamide (Diabinese), torazamide (Tolinase), and tolbutamide (Orinase®, Tol-Tab); rosiglitazone (Avandia®), rosiglitazone-glimepiride (Avandaryl), rosiglitazone-metformin (Amaryl®) M) contains thiazolidinediones, including pioglitazone (Actos®), pioglitazone-alogliptin (Oseni), pioglitazone-glimepiride (Duetact), and pioglitazone-metformin (Actoplus Met, Actoplus Met XR).

[0151] Disclosed herein are pharmaceutical antibody preparations. These pharmaceutical antibody preparations may be used for therapeutic applications. In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, for example, anti-Gal3 antibody. In some embodiments, the antibody is one of the anti-Gal3 antibodies disclosed herein or otherwise known in the art, for example, as described in Patent Document 2. The pharmaceutical antibody preparation may also contain one or more excipients, diluents, salts, and buffers, etc., which impart desirable properties to the preparation, such as improved stability, reduced aggregation, and isotonicity and pH modulation. It is assumed that one or more excipients, diluents, salts, and buffers, etc., that are generally known in the art may be used in the pharmaceutical antibody preparations disclosed herein, and / or may be used as acceptable substitutes for any of the excipients, diluents, salts, and buffers, etc., used in the pharmaceutical antibody preparations disclosed herein, and the determination of the optimal preparation of excipients, diluents, salts, and buffers, etc., is within the capabilities of those skilled in the art. The inclusion of one or more excipients, diluents, salts, and buffers may be adjusted for the treatment of a particular disease, such as coronavirus infection, or inflammation associated with said disease, and / or may be optimized to improve the stability of the pharmaceutically acceptable antibody preparation under storage conditions.

[0152] Disclosed in some embodiments is a pharmaceutical antibody preparation comprising an antibody and one or more excipients. One or more excipients may be used to improve the stability of the anti-Gal3 antibody under storage conditions and / or to improve biocompatibility when administered to a subject. One or more excipients may include small molecules, amino acids, peptides, proteins, nucleic acids, DNA, RNA, lipids, ionic compounds, salts, carbohydrates, sugars, sugar alcohols, acids, bases, surfactants, detergents, or other excipients known in the art. In some embodiments, the pharmaceutical antibody preparation has a specific pH that improves the stability of the anti-Gal3 antibody under storage conditions and / or improves biocompatibility when administered to a subject. In some embodiments, one or more excipients are used to adjust the pH to a desired level. In some embodiments, the pH of the pharmaceutical antibody preparation is adjusted to the desired pH after the addition of one or more excipients (e.g., a compatible acid or base, e.g., HCl, H2SO4, acetic acid, quer). The solution is adjusted by the addition of nitrate, phosphoric acid, NaOH, KOH, etc. The pharmaceutical antibody preparation may be acidic, basic, or neutral. In some embodiments, the antibody is an anti-Gal3 antibody.

[0153] In some embodiments of the pharmaceutical antibody formulations disclosed herein, comprising an antibody and one or more excipients, the one or more excipients comprise one or more amino acids, one or more salts, one or more surfactants, or any combination thereof. In some embodiments, the one or more amino acids may comprise alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, or any combination thereof. The one or more amino acids used as excipients may be L-stereoisomers or D-stereoisomers. In some embodiments, the one or more amino acids may be in the form of small peptides, such as dipeptides, tripeptides, tetrapeptides, or larger ones. Some embodiments of the pharmaceutical antibody formulations comprise histidine or methionine, or both. In some embodiments, histidine or methionine, or both, are L-stereoisomers or D-stereoisomers. Other amino acids, as substitutes for histidine or methionine, or both, or as additions to histidine or methionine, or both, are also considered in some embodiments, depending on the desired properties to be conferred to the formulation, such as improved stability, pH adjustment, and suitability for the intended target. Some non-limiting embodiments of the pharmaceutical antibody formulation may include 1) histidine and methionine, 2) histidine and one or more other amino acids, 3) methionine and one or more other amino acids, 4) one or more amino acids other than histidine and methionine (e.g., one or more of arginine, glycine, or glutamic acid), or 5) histidine, methionine, and one or more other amino acids (e.g., one or more of arginine, glycine, or glutamic acid). In some embodiments, the antibody is an anti-Gal3 antibody.

[0154] In some embodiments of the pharmaceutical antibody formulations disclosed herein, which include an antibody and one or more excipients, including one or more amino acids disclosed herein, the one or more excipients include one or more salts. In some embodiments, the one or more salts may include salts conventionally used as excipients. In some embodiments, the one or more salts may include chloride salts, phosphates, carbonates, bicarbonates, citrates, ascorbic acid salts, acetates, succinates, Tris salts, borates, sulfates, ammonia salts, metal salts, sodium salts, potassium salts, calcium salts, magnesium salts, organic salts, amino acid salts, nucleic acid salts, aromatic compound salts, and low-solubility salts, including any of those disclosed throughout this disclosure. The purposes of using one or more salts as excipients include, but are not limited to, improving stability and reducing antibody aggregation, equalizing the ionic charge for other components in the formulation, adjusting the solubility of other components in the formulation, adjusting pH and isotonicity, and improving biocompatibility for administration to a subject. Exemplary pharmaceutical antibody formulations disclosed herein include NaCl. However, alternative salts may also be used in place of or in addition to NaCl, including, but not limited to, those provided herein, other chloride salts, other sodium salts, ascorbic acid salts, acetate salts, phosphate salts, citrate salts, Tris salts, or succinates, or those otherwise known in the art. In some embodiments, the antibody is an anti-Gal3 antibody.

[0155] In some embodiments of the pharmaceutically antibody preparations disclosed herein, which include an antibody and one or more excipients, the one or more excipients include one or more surfactants. In some embodiments, the one or more surfactants may include surfactants that have been conventionally used as excipients. In some embodiments, the one or more surfactants may be polysorbates, polysorbates, and The surfactants may also include other surfactants commonly known and used as excipients in the art, encompassing resorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, oil, poloxamer, poloxamer 188, polyglycosides, cetyl alcohol, cocamide, stearate, laurate, nonoxynol, octoxynol, or any of those disclosed throughout this disclosure. In some embodiments, the surfactants may also act as wetting agents, detergent agents, or emulsifiers, depending on the specific surfactant and intended purpose. The purposes of these surfactants in pharmaceutically antibody formulations may include, but are not limited to, improving the solubility of the antibody or other excipients, improving the stability of the antibody, and preventing antibody aggregation. Exemplary pharmaceutically antibody formulations disclosed herein include polysorbate. In some embodiments, the polysorbate may be polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80, or any combination thereof. In some embodiments, the polysorbate is polysorbate 80. However, alternative surfactants may also be used instead of or in addition to polysorbate, including, but not limited to, those provided herein, such as poloxamer 188, or others known in the art. In some embodiments, the antibody is an anti-Gal3 antibody.

[0156] In some embodiments of the pharmaceutically antibody formulations disclosed herein, which include an antibody and one or more excipients, comprising one or more amino acids, one or more salts, and / or one or more surfactants disclosed herein, the one or more excipients may also comprise one or more sugars or sugar alcohols. In some embodiments, the one or more sugars or sugar alcohols comprise those conventionally used as excipients. In some embodiments, the sugars comprise, but are not limited to, erythrose, arabinose, ribose, deoxyribose, xylose, galactose, glucose (dextrose), fructose, isomaltose, lactose, maltose, sucrose, trehalose, maltodextrin, chitosan, dextrin, dextran, dextran 40, cellulose, or starch, or any of the others disclosed throughout this disclosure, which are generally known in the art and used as excipients. In some embodiments, sugar alcohols include, but are not limited to, glycerol, erythritol, arabitol, xylitol, ribitol, deoxyribitol, mannitol, sorbitol, galactitol, isomalt, maltitol, or lactitol, or any other sugar alcohols commonly known in the art and used as excipients, as disclosed throughout this disclosure. The purpose of these sugars and sugar alcohols in pharmaceutical antibody formulations may include, but are not limited to, improving stability and preventing antibody aggregation. Exemplary pharmaceutical antibody formulations disclosed herein may contain sugars or sugar alcohols, or both. In some embodiments, the exemplary pharmaceutical antibody formulations contain sucrose and / or mannitol. However, alternative sugars and sugar alcohols may be used instead of or in addition to sucrose and / or mannitol, including, but are not limited to, those provided herein, such as sorbitol, trehalose, dextrose, dextran, or dextran 40.In some embodiments, formulations intended for subcutaneous use contain one or more of the sugars or sugar alcohols disclosed herein, including sucrose and / or mannitol. In some embodiments, formulations intended for intravenous use may not contain one or more of the sugars or sugar alcohols disclosed herein, including sucrose and / or mannitol. In some embodiments, the antibody is an anti-Gal3 antibody.

[0157] In some embodiments, the pharmaceutical antibody preparation contains an antibody. In some embodiments, The antibody is an anti-Gal3 antibody. In some embodiments, the anti-Gal3 antibody is one of the anti-Gal3 antibodies disclosed herein or otherwise known in the art, for example, disclosed in Patent Document 2. The anti-Gal3 antibody may be a full-length antibody, a Fab fragment, an F(ab')2 fragment, scFv, sdAb, a monovalent fragment, or any other modified antibody known in the art, including bispecific, trispecific, and other polyspecific variants. The anti-Gal3 antibody generally contains a complementation-determining region (CDR). In some embodiments, the anti-Gal3 antibody is a heavy chain CDR1(V H -CDR1), heavy chain CDR2(V H -CDR2), heavy chain CDR3(V H -CDR3) and / or light chain CDR1(V L -CDR1), light chain CDR2(V L -CDR2), or light chain CDR3 (V L -CDR3), or any combination thereof may be included. In some embodiments, the antibody has the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L-Includes CDR3. In some embodiments, exemplary CDR sequences are depicted in Figures 8-13. In some embodiments, each CDR may have up to 1, 2, 3, 4, or 5 amino acids that are modified from the described sequence. In some embodiments, each CDR may have a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequences depicted in Figures 8-13. In some embodiments, each CDR may have a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequences depicted in Figures 8-13. In some embodiments, the anti-Gal3 antibody includes a VH having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 298. In some embodiments, the anti-Gal3 antibody comprises VH having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 298. In some embodiments, the anti-Gal3 antibody comprises VL having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 375. In some embodiments, the anti-Gal3 antibody comprises VL having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 375. The pharmaceutical antibody preparation may contain one or more excipients. In some embodiments, one or more excipients are present in amounts optimized for a particular disease or disorder to improve stability and / or biocompatibility when administered to a subject.In some embodiments, one or more excipients are at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 5 6, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 1 13, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 1 Concentrations of 59, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, or 200 mM, or the concentrations mentioned above. The excipients may also be present in concentrations within any of the ranges defined by any two of the degrees. One or more excipients may also be present in concentrations of at least 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 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%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%, or any combination within any two of the above concentrations. In some embodiments, the pharmaceutical antibody preparation further comprises one or more amino acids, one or more salts, or one or more surfactants (which may constitute one or more excipients). One or more amino acids, one or more salts, and one or more surfactants may be any one of the amino acids, salts, and surfactants disclosed herein. In some embodiments, one or more amino acids are present at 10–50 mM or about 10–about 50 mM. In some embodiments, one or more amino acids are present at 20 mM or about 20 mM. In some embodiments, one or more salts are present at 50–150 mM or about 50–about 150 mM. In some embodiments, one or more salts are present at 100 mM or about 100 mM. In some embodiments, one or more surfactants are present at 0.01%–0.04% or about 0.01%–about 0.04%. In some embodiments, one or more surfactants are present at 0.02% or about 0.02%. In some embodiments, the formulation has a pH of 5.3–6.3. In some embodiments, the formulation has a pH of 5.8 or about 5.8. In some embodiments, the antibody is derived from the heavy and light chain sequences depicted in Figure 18, specifically the VL sequence, VH sequence, VL / VH pairing, and / or V L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, V H- Containing one or more sequences that have 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 with any set of CDR3s (which include one or more 1, 2, 3, 4, or 5 amino acid substitutions in any one of these CDRs).

[0158] In some embodiments, the pharmaceutical antibody preparation includes an antibody. In some embodiments, the antibody is an anti-Gal3 antibody. In some embodiments, the anti-Gal3 antibody is one of the anti-Gal3 antibodies disclosed herein or otherwise known in the art, for example, disclosed in Patent Document 2. In some embodiments, the antibody has the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L-Includes CDR3. In some embodiments, exemplary CDR sequences are depicted in Figures 8-13. In some embodiments, each CDR may have up to 1, 2, 3, 4, or 5 amino acids that are modified from the described sequence. In some embodiments, the anti-Gal3 antibody includes a VH having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 298. In some embodiments, the anti-Gal3 antibody includes a VH having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 298. In some embodiments, the anti-Gal3 antibody includes one having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 375. In some embodiments, the anti-Gal3 antibody includes one having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 375. In some embodiments, the pharmaceutical antibody preparation further comprises one or more amino acids, one or more salts, or one or more surfactants. In some embodiments, the one or more amino acids include histidine and / or methionine, the one or more salts include sodium chloride (NaCl), and the one or more surfactants include polysorbate, or any combination thereof. In some embodiments, the pharmaceutical antibody preparation includes histidine, The solution comprises methionine, NaCl, or polysorbate, or any combination thereof, including histidine, methionine, NaCl, and polysorbate. In some embodiments, histidine may be L-histidine. In some embodiments, L-histidine is present in an amount or concentration of 10–50 mM or about 10–about 50 mM, or any amount or concentration assumed herein. In some embodiments, L-histidine is present in an amount or concentration of 20 mM or about 20 mM. In some embodiments, methionine is present in an amount or concentration of 2–10 mM or about 2–about 10 mM, or any amount or concentration assumed herein. In some embodiments, methionine is present in an amount or concentration of 5 mM or about 5 mM. In some embodiments, NaCl is present in an amount or concentration of 50–150 mM or about 50–about 150 mM, or any amount or concentration assumed herein. In some embodiments, NaCl is present in an amount or concentration of 100 mM or about 100 mM. In some embodiments, the polysorbate comprises polysorbate-20, polysorbate-40, polysorbate-60, polysorbate-80, or any combination thereof. In some embodiments, the polysorbate is or comprises polysorbate-80. In some embodiments, polysorbate-80 is present in an amount or concentration of 0.01% to 0.04% or about 0.01% to about 0.04%, or any amount or concentration assumed herein. In some embodiments, polysorbate-80 is present in an amount of 0.02% or about 0.02%. In some embodiments, the formulation has a pH of 5.3 to 6.3. In some embodiments, the formulation has a pH of 5.8 or about 5.8. In some embodiments, the antibody comprises the VL sequence, VH sequence, VL / VH pairing, and / or V from the heavy and light chain sequences depicted in Figure 18. L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, V H- Containing one or more sequences that have 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 with any set of CDR3s (which include one or more 1, 2, 3, 4, or 5 amino acid substitutions in any one of these CDRs).

[0159] In some embodiments, the formulation contains one or more of the following: polysorbate 80, polysorbate 20, poloxamer 188, mannitol, sorbitol, sucrose, trehalose, dextrose, dextran 40, NaCl, arginine, glycine, methionine, ascorbic acid, NaOAc, phosphate, citrate, acetate, tris, succinate, and histidine.

[0160] In some embodiments, a pharmaceutical antibody preparation is provided. The preparation may contain a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L- Containing CDR3, the formulation may contain histidine, methionine, NaCl, and polysorbate. In some embodiments, the formulation may have a pH of 5.3 to 6.3, which may or may not be achieved by the addition of histidine, methionine, NaCl, and / or polysorbate. In some embodiments, the antibody contains a heavy chain variable domain (VH) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 298. In some embodiments, the antibody contains a heavy chain variable domain (VH) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 298. In some embodiments, the antibody contains a light chain variable domain (VL) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 375. In some embodiments, the antibody is at least 80%, 85%, and 90% of the sequence of SEQ ID NO: 375. , including light chain variable domain (VL) regions having sequences that are 95%, 99%, or 100% similar. In some embodiments, the formulation may also include additional components and / or excipients to those listed, or one or more of the options stated positively may be excluded. In some embodiments, components and / or excipients may be replaced with one or more substitutes that function to achieve the same result, or may be used in addition thereto. In some embodiments, histidine may be replaced with an alternative buffer having an appropriate pKa. In some embodiments, histidine may be replaced with a substitute having the same buffering capacity. In some embodiments, histidine may be replaced with another amino acid. In some embodiments, histidine may be replaced with a substitute that exhibits the same or similar antibody-protective effect. In some embodiments, histidine may be replaced with a substitute that exhibits the same or similar ability to reduce antibody aggregation. In some embodiments, histidine may be replaced with a substitute that has the same or similar cryoprotective capacity. In some embodiments, methionine may be replaced with an alternative buffer having an appropriate pKa. In some embodiments, methionine may be replaced with an alternative having the same buffering capacity. In some embodiments, methionine may be replaced with another amino acid. In some embodiments, methionine may be replaced with an alternative having the same or similar antioxidant effect. In some embodiments, methionine may be replaced with an alternative having the same antibody-protective effect. In some embodiments, methionine may be replaced with an alternative having the same or similar protein-stabilizing effect. In some embodiments, methionine may be replaced with an alternative having the same or similar ability to reduce antibody aggregation, including alternatives that may exhibit one or more of the properties provided herein. Alternatives for histidine and / or methionine may be any of those provided herein, e.g., arginine or glycine, or any others known in the art. In some embodiments, NaCl may be replaced with another salt.In some embodiments, NaCl may be replaced with a substitute having the same or similar water solubility. In some embodiments, NaCl may be replaced with a substitute having the same or similar effect on the formulation isotonicity. In some embodiments, NaCl may be replaced with a substitute having the same or similar protein stabilizing effect, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for NaCl may be any of those provided herein, e.g., other chloride salts, other sodium salts, ascorbic acid salts, acetate salts, phosphate salts, citrate salts, Tris salts, or succinates, or any others known in the art. In some embodiments, polysorbate may be replaced with another surfactant and / or detergent. In some embodiments, polysorbate may be replaced with a substitute having the same or similar surfactant ability / effect. In some embodiments, polysorbate may be replaced with a substitute having the same or similar ability to solubilize antibodies and / or other excipients. In some embodiments, polysorbate may be replaced with a substitute having the same or similar ability to reduce antibody aggregation. In some embodiments, polysorbate may be replaced with a substitute having the same or similar protein stabilization effect, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for polysorbate may be any of those provided herein, e.g., poloxamer 188, or any others known in the art. In some embodiments, pH may be acidic, basic, or neutral. In some embodiments, pH may be basic. In some embodiments, pH may be modified. In some embodiments, pH may be increased or decreased to match the characteristics of the components, excipients, and / or buffers used in the formulation, as well as the antibody species used, and / or the amounts of the antibody, component, or excipient used. In some embodiments, pH may be increased or decreased to a desired pH after the addition of the antibody, component, or excipient.Substitutes envisioned herein are excipients, diluents, and salts provided throughout this disclosure. It may also include one or more of the following: a buffer material, or a cushioning agent.

[0161] For any embodiment of the pharmaceutical antibody formulations provided herein, histidine is L-histidine, D-histidine, or racemic histidine. For any embodiment of the pharmaceutical antibody formulations provided herein, histidine is racemic histidine. For any embodiment of the pharmaceutical antibody formulations provided herein, histidine is D-histidine. In some embodiments, histidine may be replaced with an alternative buffer having an appropriate pKa. In some embodiments, histidine may be replaced with an alternative having the same buffering capacity. In some embodiments, histidine may be replaced with another amino acid. In some embodiments, histidine may be replaced with an alternative exhibiting the same or similar antibody-protective effect. In some embodiments, histidine may be replaced with an alternative exhibiting the same or similar ability to reduce antibody aggregation. In some embodiments, histidine may be replaced with an alternative having the same or similar cryoprotective capacity, including alternatives that may exhibit one or more of the properties provided herein. Substitutes for histidine may be any of those provided herein, such as arginine or glycine, or any other known in the art.

[0162] For any embodiment of the pharmaceutical antibody preparations provided herein, histidine is present in at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 16 Histidine may be present at concentrations of 4, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, or 200 mM, or at any concentration within the range defined by any two of the above concentrations. In some embodiments, histidine is present at 10 to 50 mM, for example, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mM. In some embodiments, histidine is present at 20 mM or about 20 mM. In some embodiments where histidine is L-histidine, L-histidine is present at concentrations of 10–50 mM, for example, 10, 15, 20, 25, 30, 35, 40, 45, or 50 mM.In some embodiments, where histidine is L-histidine, L-histidine is present at 20 mM or about 20 mM.

[0163] For any embodiment of the pharmaceutical antibody formulations provided herein, methionine is L-methionine, D-methionine, or racemic methionine. For any embodiment of the pharmaceutical antibody formulations provided herein, methionine is racemic methionine. For any embodiment of the pharmaceutical antibody formulations provided herein, methionine is D-methionine. In some embodiments, methionine is It can be replaced with an alternative buffer having an appropriate pKa. In some embodiments, methionine can be replaced with an alternative having the same buffering capacity. In some embodiments, methionine can be replaced with another amino acid. In some embodiments, methionine can be replaced with an alternative having the same or similar antioxidant effect. In some embodiments, methionine can be replaced with an alternative having the same antibody-protective effect. In some embodiments, methionine can be replaced with an alternative having the same or similar protein-stabilizing effect. In some embodiments, methionine can be replaced with an alternative having the same or similar ability to reduce antibody aggregation, including alternatives that may exhibit one or more of the properties provided herein. Alternatives for methionine may be any of those provided herein, e.g., arginine or glycine, or any others known in the art.

[0164] For any embodiment of the pharmaceutical antibody preparations provided herein, methionine is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 16 Methionine may be present at concentrations of 4, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, or 200 mM, or at any concentration within the range defined by any two of the above concentrations. In some embodiments, methionine is present at 2–10 mM, for example, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mM. In some embodiments, methionine is present at 5 mM or about 5 mM.

[0165] For any embodiment of the pharmaceutical antibody preparations provided herein, NaCl is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 ,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,1 21, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 1 It may be present at concentrations of 56, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, or 200 mM, or at any concentration within the range defined by any two of the above concentrations. In some embodiments, NaCl is present at 50–150 mM, for example, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 mM. In some embodiments, NaCl is present at 100 mM. In some embodiments, NaCl may be replaced with another salt. In some embodiments, NaCl may be replaced with a substitute having the same or similar water solubility. In some embodiments, NaCl may be replaced with a substitute having the same or similar effect on the formulation isotonicity. In some embodiments, NaCl may be replaced with a substitute having the same or similar protein stabilizing effect, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for NaCl may be any of those provided herein, e.g., other chloride salts, other sodium salts, ascorbic acid salts, acetate salts, phosphate salts, citrate salts, Tris salts, or succinates, or any others known in the art.

[0166] For any embodiment of the pharmaceutical antibody formulations provided herein, the polysorbate comprises polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or any combination thereof. In some embodiments, the polysorbate comprises, essentially consists of, or comprises polysorbate 80. In some embodiments, the polysorbate may be present in concentrations of at least 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 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%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%, or any combination within any two of the above concentrations. In some embodiments, the polysorbate may be present in concentrations of 0.01% to 0.04%, for example, 0.01%, 0.02%, 0.03%, or 0.04%. In some embodiments, the polysorbate is present in an amount of about 0.01% to about 0.04%, for example, about 0.01%, about 0.02%, about 0.03%, or about 0.04%. In some embodiments, the polysorbate is present in an amount of 0.02% or about 0.02%. In some embodiments where the polysorbate is polysorbate 80, the polysorbate 80 is present in an amount of 0.01% to about 0.04%, for example, about 0.01%, 0.02%, 0.03%, or 0.04%. In some embodiments where the polysorbate is polysorbate 80, the polysorbate 80 is present in an amount of about 0.01% to about 0.04%, for example, about 0.01%, about 0.02%, about 0.03%, or about 0.04%. In some embodiments, the polysorbate 80 is present in an amount of 0.02% or about 0.02%. In some embodiments, polysorbate may be replaced with another surfactant and / or detergent. In some embodiments, polysorbate may be replaced with a substitute having the same or similar surfactant ability / effect. In some embodiments, polysorbate may be replaced with a substitute having the same or similar ability to solubilize antibodies and / or other excipients.In some embodiments, polysorbate may be replaced with a substitute having the same or similar ability to reduce antibody aggregation. In some embodiments, polysorbate may be replaced with a substitute having the same or similar protein stabilization effect, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for polysorbate may be any of those provided herein, e.g., poloxamer 188, or any others known in the art.

[0167] For any embodiment of the pharmaceutically acceptable antibody formulations provided herein, the pH is approximately 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, or 6.3. In some embodiments, the pH is approximately 5.8. In some embodiments, the pH is 5.8. In some embodiments, the pH can be acidic, basic, or neutral. In some embodiments, the pH can be modified. In some embodiments, the pH can be increased or decreased to match the characteristics of the components, excipients, and / or buffers used in the formulation, as well as the antibody species used, and / or the amounts of the antibody, component, or excipient used. In some embodiments, the pH can be increased or decreased to a desired pH after the addition of the antibody, component, or excipient.

[0168] For any embodiment of the pharmaceutical antibody formulations provided herein, the formulation further comprises one or more sugars or one or more sugar alcohols, or both, for example, sugars or sugar alcohols disclosed herein or otherwise known in the art. In some embodiments, one or more sugars comprises sucrose. In some embodiments, one or more sugar alcohols comprises mannitol. In some embodiments, the formulation comprises sucrose or mannitol, or both. In some embodiments, the formulation comprises sucrose and mannitol. In some embodiments, sucrose and / or mannitol may be replaced with another sugar and / or sugar alcohol. In some embodiments, sucrose and / or mannitol may be replaced with a substitute having the same or similar antibody-protective effect. In some embodiments, sucrose and / or mannitol may be replaced with a substitute exhibiting the same or similar ability to reduce antibody aggregation. In some embodiments, sucrose and / or mannitol may be replaced with a substitute having the same or similar cryoprotective ability. In some embodiments, sucrose and / or mannitol may be replaced with substitutes having the same effect on isotonicity, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for sucrose and / or mannitol may be any of those provided herein, e.g., sorbitol, trehalose, dextrose, dextran, or dextran 40, or any others known in the art.

[0169] In some embodiments, one or more sugars or one or more sugar alcohols may be present in concentrations of at least 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 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%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%, or any combination within any two of the above concentrations. In some embodiments, one or more sugars or one or more sugar alcohols may be present in concentrations of 2% to 5%, for example, 2%, 3%, 4%, or 5%. In some embodiments, one or more sugars or one or more sugar alcohols are present in amounts of about 2% to about 5%, for example, about 2%, about 3%, about 4%, or about 5%. In some embodiments where the sugar is sucrose, sucrose is present in amounts of 2% to 5% or about 2% to 5%. In some embodiments where the sugar alcohol is mannitol, mannitol is present in amounts of 2% to 5% or about 2% to 5%.

[0170] For any embodiment of the pharmaceutical antibody preparations provided herein, the preparation is configured for parenteral administration. In some embodiments, the preparation is configured for subcutaneous administration. In embodiments where the preparation is configured for subcutaneous administration, the preparation may contain one or more sugars and / or one or more sugar alcohols. In some embodiments, the preparation configured for subcutaneous administration contains sucrose or mannitol, or both. In some embodiments, the formulation is configured for intravenous administration. In embodiments where the formulation is configured for intravenous administration, the formulation may not contain one or more sugars and / or one or more sugar alcohols. In some embodiments, the formulation configured for intravenous administration does not contain sucrose or mannitol, or both.

[0171] For any embodiment of the pharmaceutical antibody preparations provided herein, the antibody may be present in a unit dose of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 mg. , or may be present in an amount of approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 mg, or in any amount within the range defined by any two of the above amounts. In some embodiments, the antibody is present in an amount of 1 to 50 mg as a unit dose. In some embodiments, the antibody is present in one amount of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg as a unit dose, or in any amount within the range defined by any two of the above amounts. In some embodiments, the antibody is present in an amount of 1 mg. In some embodiments, the antibody is present in an amount of 5 mg. In some embodiments, the antibody is present in an amount of 10 mg. In some embodiments, the antibody is present in an amount of 20 mg. In some embodiments, the antibody is present in an amount of 40 mg. In some embodiments, the antibody is present in an amount of 50 mg. In some embodiments, the antibody is present in the formulation at one concentration of 1 mg / mL, 5 mg / mL, 10 mg / mL, 20 mg / mL, 40 mg / mL, or 50 mg / mL, or in any concentration within the range defined by any two of the above concentrations. In some embodiments, the antibody is present at a concentration of 1 mg / mL. In some embodiments, the antibody is present at a concentration of 5 mg / mL. In some embodiments, the antibody is present at a concentration of 10 mg / mL. In some embodiments, the antibody is present at a concentration of 20 mg / mL.In some embodiments, the antibody is present at a concentration of 40 mg / mL. In some embodiments, the antibody is present at a concentration of 50 mg / mL.

[0172] In some embodiments of the pharmaceutical antibody preparation, L-histidine is present at approximately 20 mM, methionine at approximately 5 mM, NaCl at approximately 100 mM, polysorbate 80 at approximately 0.02%, sucrose at 2–5%, mannitol at 2–5%, the pH of the preparation is approximately 5.8, and the therapeutically effective dose of the antibody is any amount within the range defined by one of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg as a unit dose, or any two of the above amounts. In some embodiments of the pharmaceutical antibody preparation, L-histidine is present at approximately 20 mM, methionine at approximately 5 mM, NaCl at approximately 100 mM, polysorbate 80 at approximately 0.02%, sucrose at 2-5%, mannitol at 2-5%, the pH of the preparation is approximately 5.8, and the therapeutically effective dose of the antibody is 1 mg per unit dose. In some embodiments of the pharmaceutical antibody preparation, L-histidine is present at approximately 20 mM, methionine at approximately 5 mM, NaCl at approximately 100 mM, polysorbate 80 at approximately 0.02%, sucrose at 2-5%, mannitol at 2-5%, and the pH of the preparation is approximately The pH is 5.8, and the therapeutic dose of the antibody is 10 mg per unit dose. In some embodiments of the pharmaceutical antibody preparation, L-histidine is present at approximately 20 mM, methionine at approximately 5 mM, NaCl at approximately 100 mM, polysorbate 80 at approximately 0.02%, sucrose at 2-5%, mannitol at 2-5%, the pH of the preparation is approximately 5.8, and the therapeutic dose of the antibody is 20 mg per unit dose. In some embodiments of the pharmaceutical antibody preparation, L-histidine is present at approximately 20 mM, methionine at approximately 5 mM, NaCl at approximately 100 mM, polysorbate 80 at approximately 0.02%, sucrose at 2-5%, mannitol at 2-5%, the pH of the preparation is approximately 5.8, and the therapeutic dose of the antibody is 40 mg per unit dose. In some embodiments of the pharmaceutical antibody preparation, L-histidine is present at approximately 20 mM, methionine at approximately 5 mM, NaCl at approximately 100 mM, polysorbate 80 at approximately 0.02%, sucrose at 2-5%, mannitol at 2-5%, the pH of the preparation is approximately 5.8, and the therapeutically effective dose of the antibody is 50 mg as a unit dose.

[0173] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody. In some embodiments, the antibody has the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L-Contains CDR3. In some embodiments, the antibody is present in an amount as a unit dose of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg, or in an amount as a unit dose within the range defined by any two of the above amounts. In some embodiments, the antibody is present in an amount of 1 mg. In some embodiments, the antibody is present in an amount of 5 mg. In some embodiments, the antibody is present in an amount of 10 mg. In some embodiments, the antibody is present in an amount of 20 mg. In some embodiments, the antibody is present in an amount of 40 mg. In some embodiments, the antibody is present in an amount of 50 mg. In some embodiments, the pharmaceutically acceptable antibody preparation further comprises L-histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, and polysorbate 80 present at 0.02%. In some embodiments, the pH of the preparation is approximately 5.8. In some embodiments, the pharmaceutically acceptable antibody preparation further comprises sucrose and / or mannitol. In some embodiments, sucrose is present in the preparation at 2-5%. In some embodiments, mannitol is present in the formulation at a concentration of 2-5%.

[0174] In some embodiments of the pharmaceutical antibody formulations disclosed herein, the formulation is configured for parenteral administration. In some embodiments, the formulation is configured for subcutaneous administration. In some embodiments, the formulation configured for subcutaneous administration contains sucrose or mannitol, or both. In some embodiments, the formulation is configured for intravenous administration. In some embodiments, the formulation configured for intravenous administration does not contain sucrose or mannitol, or both.

[0175] When applied to any embodiment of the pharmaceutical antibody preparation disclosed herein, the pharmaceutical antibody preparation is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 5 5, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 mg / mL, or approximately 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 ,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69 The antibody is prepared at a concentration of 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 mg / mL, or at any concentration within the range defined by any two of the above concentrations. In some embodiments, the pharmaceutical antibody preparation is prepared at a concentration of 0.3, 0.8, 2.8, 8.4, or 10 mg / mL, or about 0.3, about 0.8, about 2.8, about 8.4, or about 10 mg / mL. In some embodiments, the pharmaceutical antibody preparation is prepared at a concentration of 20 mg / mL or about 20 mg / mL. In some embodiments, the pharmaceutical antibody preparation is prepared at a concentration of 50 mg / mL or about 50 mg / mL.

[0176] When applied to any of the embodiments disclosed herein, the pharmaceutical antibody formulation remains stable by at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% over three months. In some embodiments, the pharmaceutical antibody formulation remains stable by at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or 100% over three months at either 5°C or 25°C / 60% relative humidity (RH).

[0177] In some embodiments of the pharmaceutical antibody formulations disclosed herein, the antibody includes a heavy chain variable domain (VH) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 298. In some embodiments of the pharmaceutical antibody formulations disclosed herein, the antibody includes a heavy chain variable domain (VH) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 298. In some embodiments, the antibody includes a light chain variable domain (VL) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 375. In some embodiments, the antibody includes a light chain variable domain (VL) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 375. In some embodiments, the antibody includes a VH region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 298, and the antibody includes a VL region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 375. In some embodiments, the antibody includes a VH region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 298, and the antibody includes a VL region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 375. In some embodiments, the antibody includes a VH region having the sequence of SEQ ID NO: 298. In some embodiments, the antibody includes a VL region having the sequence of SEQ ID NO: 375. In some embodiments, the antibody includes a VH region having the sequence of SEQ ID NO: 298, and the antibody includes a VL region having the sequence of SEQ ID NO: 375. In some embodiments, the antibody includes a heavy chain (HC) having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 449. In some embodiments, the antibody includes a heavy chain (HC) having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 449.In some embodiments, the antibody comprises a light chain (LC) having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 496. This includes: In some embodiments, the antibody contains an HC having the sequence of SEQ ID NO: 449. In some embodiments, the antibody contains an LC having the sequence of SEQ ID NO: 496. In some embodiments, the antibody is TB006(4A11.H3L1, IMT006a, IMT006-5). The percentage of identity or similarity between two sequences is well understood in the art and can be calculated by the number of conserved or similar amino acids or nucleotides compared to the length of the sequences.

[0178] In some embodiments of the pharmaceutical antibody preparations disclosed herein, the antibody or its components are encoded by one or more nucleic acids. In some embodiments, the antibody includes VH encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% identity to the nucleic acid sequence of SEQ ID NO: 540. In some embodiments, the antibody includes VL encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% identity to the nucleic acid sequence of SEQ ID NO: 622. In some embodiments, the antibody includes VH encoded by the nucleic acid sequence of SEQ ID NO: 540. In some embodiments, the antibody includes VL encoded by the nucleic acid sequence of SEQ ID NO: 622. In some embodiments, the antibody includes HC encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% identity to the nucleic acid sequence of SEQ ID NO: 704. In some embodiments, the antibody comprises an LC encoded by a nucleic acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% identity to the nucleic acid sequence of SEQ ID NO: 751. In some embodiments, the antibody comprises an HC encoded by the nucleic acid sequence of SEQ ID NO: 704. In some embodiments, the antibody comprises an LC encoded by the nucleic acid sequence of SEQ ID NO: 751. The percentage of identity between the two sequences is well understood in the art and can be calculated by the number of conserved amino acids or nucleotides compared to the length of the sequence.

[0179] In some embodiments, pharmaceutical formulations include, but are not limited to, aqueous liquid dispersions, self-emulsifying dispersions, solid solutions, liposome dispersions, aerosols, solid dosing forms, powders, immediate-release formulations, controlled-release formulations, rapid-dissolving formulations, tablets, capsules, pills, delayed-release formulations, sustained-release formulations, pulsatile-release formulations, multi-particle formulations (e.g., nanoparticle formulations), and mixed immediate- and controlled-release formulations.

[0180] In some embodiments, the pharmaceutical formulation further comprises a pH adjuster or buffering agent, which includes acids such as acetic acid, boric acid, citric acid, lactic acid, phosphoric acid, and hydrochloric acid; bases such as sodium hydroxide, sodium phosphate, sodium borate, sodium citrate, sodium acetate, sodium lactate, and tris-(hydroxymethyl)aminomethane; and buffering agents such as citrate / dextrose, sodium bicarbonate, and ammonium chloride. Such acids, bases, and buffering agents are included in amounts required to maintain the pH of the formulation within an acceptable range.

[0181] In some embodiments, the pharmaceutical formulation contains one or more salts in amounts required to bring the weight osmolality of the formulation within an acceptable range. Such salts include those having sodium, potassium, or ammonium cations and chloride, citric acid, ascorbic acid, boric acid, phosphoric acid, bicarbonate, sulfuric acid, thiosulfate, or bisulfite anions; preferred salts include sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfite, and ammonium sulfate.

[0182] In some embodiments, the pharmaceutical formulation further includes a diluent used to stabilize the compound so that a more stable environment can be provided. Salts dissolved in buffered solutions (which can also provide pH control or maintenance) are used as diluents in the art and include, but are not limited to, phosphate-buffered saline solutions. Certain examples In this process, the diluent increases the volume of the formulation to facilitate compression or creates a sufficient volume for a homogeneous blend for capsule filling. Such compounds may include, for example, lactose, starch, mannitol, sorbitol, dextrose, microcrystalline cellulose, e.g., Avicel®; dibasic calcium phosphate, dicalcium phosphate dihydrate; tricalcium phosphate, calcium phosphate; anhydrous lactose, spray-dried lactose; pregelatinized starch, compressed sugar, e.g., Di-Pac (Amstar); mannitol, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose stearate acetate, sucrose-based diluents, powdered sugar; monobasic calcium sulfate monohydrate, calcium sulfate dihydrate; calcium lactate trihydrate, dextrose; hydrolyzed cereal solids, amylose; powdered cellulose, calcium carbonate; glycine, kaolin; mannitol, sodium chloride; inositol, and bentonite.

[0183] In some embodiments, the pharmaceutical formulation is formulated for administration to a subject via one or more routes of administration, including but not limited to parenteral (e.g., intravenous, subcutaneous, intramuscular, intra-arterial, intradermal, intraperitoneal, intravitreous, intracerebral, or intraventricular), oral, intranasal, buccal, rectal, or transdermal administration routes. In some embodiments, the pharmaceutical formulations described herein are formulated for parenteral (e.g., intravenous, subcutaneous, intramuscular, intra-arterial, intradermal, intraperitoneal, intravitreous, intracerebral, or intraventricular) administration. In some embodiments, the pharmaceutical antibody formulation is formulated for intravenous administration. In some embodiments, the pharmaceutical antibody formulation is formulated for subcutaneous administration. The appropriate formulation depends on the selected route of administration. Techniques for the formulation and administration of the compounds described herein are known to those skilled in the art.

[0184] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody. In some embodiments, the antibody is an anti-Gal3 antibody.

[0185] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate.

[0186] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, and the preparation has a pH of 5.3 to 6.3.

[0187] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, and the preparation has a pH of 5.3 to 6.3. In some embodiments, the histidine is L-histidine. In some embodiments, the polysorbate is polysorbate 80. In some embodiments, the histidine is L-histidine and the polysorbate is polysorbate 80. In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, and the preparation has a pH of 5.3 to 6.3, and the histidine is L-histidine. In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, and the preparation has a pH of 5.3 to 6.3, and the polysorbate is polysorbate 80. In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, the preparation having a pH of 5.3 to 6.3, the histidine being L-histidine, and the polysorbate being polysorbate 80. In some embodiments, the antibody is an anti-Gal3 antibody.

[0188] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, the preparation has a pH of 5.3 to 6.3, and the histidine is present at 10 to 50 mM. In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, the preparation The preparation has a pH of 5.3 to 6.3 and histidine is present at 20 mM. In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, the preparation has a pH of 5.3 to 6.3, and methionine is present at 2 to 10 mM. In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, the preparation has a pH of 5.3 to 6.3, and methionine is present at 5 mM. In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, the preparation has a pH of 5.3 to 6.3, and NaCl is present at 50 to 150 mM. In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, with a pH of 5.3 to 6.3 and 100 mM NaCl. In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, with a pH of 5.3 to 6.3 and 0.01 to 0.04% polysorbate. In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, histidine, methionine, NaCl, and polysorbate, with a pH of 5.3 to 6.3 and 0.02% polysorbate. In some embodiments, histidine is L-histidine. In some embodiments, polysorbate is polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80. In some embodiments, the polysorbate is polysorbate 80. In some embodiments, the pH is 5.8. In some embodiments, the pharmaceutical antibody preparation further contains sucrose. In some embodiments, sucrose is present in a concentration of 2% to 5%. In some embodiments, the pharmaceutical antibody preparation further contains mannitol. In some embodiments, mannitol is present in a concentration of 2% to 5%. In some embodiments, the antibody is an anti-Gal3 antibody.

[0189] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L -Containing CDR3, the formulation contains histidine, methionine, NaCl, and polysorbate, and the formulation has a pH of 5.3 to 6.3.

[0190] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L The formulation contains -CDR3, histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate at 0.02%, and the formulation has a pH of 5.3 to 6.3.

[0191] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 LThe formulation contains -CDR3, histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate at 0.02%, and the formulation has a pH of approximately 5.8.

[0192] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -C V has sequence DR1, sequence number 222. L V with sequence -CDR2; and sequence number 249 L The formulation contains -CDR3, L-histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate 80 at 0.02%, and the formulation has a pH of 5.3 to 6.3.

[0193] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L The formulation contains -CDR3, L-histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate 80 at 0.02%, and the formulation has a pH of approximately 5.8.

[0194] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H-CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L - Containing CDR3, the antibody is present in unit doses of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 40 mg, and the formulation contains histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate at 0.02%, and the formulation has a pH of 5.3 to 6.3.

[0195] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L - Containing CDR3, the antibody is present in unit doses of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg, and the formulation contains histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate at 0.02%, with the formulation having a pH of approximately 5.8.

[0196] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 LThe preparation contains CDR3, and the antibody is present in unit doses of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg. The preparation contains L-histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate 80 at 0.02%, and the preparation has a pH of 5.3 to 6.3.

[0197] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L The formulation contains CDR3, and the antibody is present in unit doses of 1 mg, 50 mg, 10 mg, 20 mg, 40 mg, or 50 mg. The formulation also contains L-histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate 80 at 0.02%, and the formulation has a pH of approximately 5.8.

[0198] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, and the antibody is sequence The antibody contains a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to sequence number 298 and a VL region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to sequence number 375, the antibody is present in unit doses of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg, the formulation contains histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate at 0.02%, and the formulation has a pH of 5.3 to 6.3.

[0199] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, the antibody comprising a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 298 and a VL region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 375, the antibody is present in units of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg, the preparation comprises histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, and polysorbate present at 0.02%, and the preparation has a pH of approximately 5.8.

[0200] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, the antibody comprising a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 298 and a VL region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 375, the antibody is present in units of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg, the preparation comprises L-histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, and polysorbate 80 present at 0.02%, and the preparation has a pH of 5.3 to 6.3.

[0201] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, the antibody comprising a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 298 and a VL region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 375, the antibody is present in units of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg, the preparation comprises L-histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, and polysorbate 80 present at 0.02%, and the preparation has a pH of approximately 5.8.

[0202] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L The preparation contains -CDR3, the antibody is present in an amount of 1 mg as a unit dose, and the preparation contains L-histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate 80 at 0.02%, and the pH is approximately 5.8.

[0203] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L -Containing CDR3, the antibody is present in an amount of 5 mg as a unit dose, and the formulation contains L-histidine present at 20 mM, methionine present at 5 mM, and present at 100 mM. It contains NaCl, 0.02% polysorbate 80, and has a pH of approximately 5.8.

[0204] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L-CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L The preparation contains CDR3, the antibody is present in an amount of 10 mg as a unit dose, and the preparation contains L-histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate 80 at 0.02%, and the pH is approximately 5.8.

[0205] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L The preparation contains CDR3, the antibody is present in a unit dose of 20 mg, and the preparation contains L-histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate 80 at 0.02%, with a pH of approximately 5.8.

[0206] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L The preparation contains CDR3, the antibody is present in an amount of 40 mg as a unit dose, and the preparation contains L-histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate 80 at 0.02%, and the pH is approximately 5.8.

[0207] In some embodiments, the pharmaceutical antibody preparation comprises a therapeutically effective amount of antibody, the antibody having the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L The preparation contains CDR3, the antibody is present in an amount of 50 mg as a unit dose, and the preparation contains L-histidine at 20 mM, methionine at 5 mM, NaCl at 100 mM, and polysorbate 80 at 0.02%, and the pH is approximately 5.8.

[0208] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, the antibody comprising a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 298 and a VL region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 375, the antibody is present in an amount of 1 mg as a unit dose, the preparation contains L-histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, polysorbate 80 present at 0.02%, and the pH is approximately 5.8.

[0209] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, wherein the antibody has a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 298 and at least 8% identical sequence to the sequence of SEQ ID NO: 375. The formulation contains VL regions with 0%, 85%, 90%, 95%, 99%, or 100% identical sequences, the antibody is present in an amount of 5 mg as a unit dose, the formulation contains L-histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, polysorbate 80 present at 0.02%, and the pH is approximately 5.8.

[0210] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, the antibody comprising a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 298 and a VL region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 375, the antibody is present in an amount of 10 mg as a unit dose, the preparation contains L-histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, polysorbate 80 present at 0.02%, and the pH is approximately 5.8.

[0211] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, the antibody comprising a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 298 and a VL region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 375, the antibody is present in an amount of 20 mg as a unit dose, the preparation contains L-histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, polysorbate 80 present at 0.02%, and the pH is approximately 5.8.

[0212] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, the antibody comprising a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 298 and a VL region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 375, the antibody is present in an amount of 40 mg as a unit dose, the preparation contains L-histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, polysorbate 80 present at 0.02%, and the pH is approximately 5.8.

[0213] In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of antibody, the antibody comprising a VH region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 298 and a VL region having at least 80%, 85%, 90%, 95%, 99%, or 100% identical sequence to the sequence of SEQ ID NO: 375, the antibody is present in an amount of 50 mg as a unit dose, the preparation contains L-histidine present at 20 mM, methionine present at 5 mM, NaCl present at 100 mM, polysorbate 80 present at 0.02%, and the pH is approximately 5.8.

[0214] Exemplary products and kits Disclosed herein are kits and products for use in certain embodiments with one or more compositions and methods described herein. Such a kit includes a carrier, package, or container partitioned to receive one or more containers, such as vials and tubes, each of which contains one of the separate elements used in the methods described herein. Preferred 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.

[0215] Products provided herein include 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 the selected formulation and the intended mode of administration and treatment.

[0216] For example, a container may include an anti-Gal3 antibody or a conjugated fragment thereof disclosed herein, host cells for producing one or more antibodies described herein, and / or a vector containing a nucleic acid molecule encoding an antibody described herein. Such a kit may optionally include an identifying description or label or instructions for its use in the method described herein.

[0217] A kit typically includes labels listing the contents and / or instructions for use, as well as a package insert with instructions for use. A set of instruction manuals is also typically included.

[0218] In one embodiment, the label is on the container or attached to the container. In one embodiment, the label is on the container if the letters, numbers or other features forming the label are attached, molded or etched onto the container itself; the label is attached to the container if it is present, for example, as a package insert, also within a receptacle or carrier that holds the container. In one embodiment, the label is used to indicate that the contents should be used for a specific therapeutic application. The label may also indicate instructions for the use of the contents, for example, in the methods described herein.

[0219] In certain embodiments, the pharmaceutical composition is provided in a pack or dispenser device containing one or more unit dosage forms containing the compound provided herein. The pack contains, for example, 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 by a warning label, as prescribed by a government agency that regulates the production, use, or sale of pharmaceuticals, which reflects agency approval of the drug form for human or veterinary administration. Such warning labels are, for example, labels approved by the U.S. Food and Drug Administration for prescription drugs or approved product inserts. In one embodiment, the composition containing the compound provided herein, formulated in a suitable pharmaceutical carrier, is also prepared, placed in a suitable container, and labeled for treatment in the indicated state.

[0220] In some embodiments, a sterile vial containing a pharmaceutical antibody preparation is provided, the preparation may contain a therapeutically effective amount of antibody. In some embodiments, the sterile vial contains any one of the pharmaceutical antibody preparations disclosed herein. In some embodiments, the antibody has the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L -Contains CDR3. In some embodiments, the antibody is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 31. H-CDR1, for sequence number 72, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%; 95%, 96%, 97%, 98%, 99%, or 100% identical V H -CDR2, for sequence number 113, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%; 95%, 96%, 97%, 98%, 99%, or 100% identical V H -CDR3, for sequence number 171, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%. 95%, 96%, 97%, 98%, 99%, Or 100% identical V L -CDR1, for sequence number 222, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%; 95%, 96%, 97%, 98%, 99%, or 100% identical V L -CDR2; and for the sequence of sequence number 249, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%; 95%, 96%, 97%, 98%, 99%, or 100% identical V L -Contains CDR3. In some embodiments, the antibody is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similar to the sequence of SEQ ID NO: 31. H -CDR1, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to the sequence of sequence 72. V is 95%, 96%, 97%, 98%, 99%, or 100% similar. H-CDR2, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to sequence 113. V is 95%, 96%, 97%, 98%, 99%, or 100% similar. H -CDR3, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to sequence 171. V is 95%, 96%, 97%, 98%, 99%, or 100% similar. L -CDR1, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to sequence 222. V is 95%, 96%, 97%, 98%, 99%, or 100% similar. L -CDR2; and the sequence of sequence number 249 are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to V. 95%, 96%, 97%, 98%, 99%, or 100% similar. L -Includes CDR3.

[0221] In some embodiments, the pharmaceutical antibody preparation may further comprise histidine, methionine, NaCl, and polysorbate. In some embodiments, the preparation may have a pH of 5.3 to 6.3. In some embodiments, the antibody may be an anti-Gal3 antibody. In some embodiments, the antibody may be an anti-Gal3 antibody disclosed herein or otherwise known in the art, e.g., disclosed in Patent Document 2. In some embodiments, the antibody comprises a heavy chain variable domain (VH) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 298. In some embodiments, the antibody comprises a heavy chain variable domain (VH) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 298. In some embodiments, the antibody includes a light chain variable domain (VL) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% identical to the sequence of SEQ ID NO: 375. In some embodiments, the antibody includes a light chain variable domain (VL) region having a sequence that is at least 80%, 85%, 90%, 95%, 99%, or 100% similar to the sequence of SEQ ID NO: 375. In some embodiments, the formulation may also include additional components and / or excipients to those listed, or one or more of the options stated positively may be excluded. In some embodiments, components and / or excipients may be replaced with one or more substitutes that function to achieve the same result, or may be used in addition thereto. In some embodiments, histidine may be replaced with an alternative buffer having an appropriate pKa. In some embodiments, histidine may be replaced with a substitute having the same buffering capacity. In some embodiments, histidine may be replaced with another amino acid. In some embodiments, histidine may be replaced with a substitute that exhibits the same or similar antibody-protective effect. In some embodiments, histidine may be replaced with a substitute that exhibits the same or similar ability to reduce antibody aggregation. They may be replaced. In some embodiments, histidine may be replaced with a substitute having the same or similar cryoprotective capacity, including substitutes that may exhibit one or more of the properties provided herein. In some embodiments, methionine may be replaced with an alternative buffer having an appropriate pKa. In some embodiments, methionine may be replaced with a substitute having the same buffering capacity. In some embodiments, methionine may be replaced with another amino acid. In some embodiments, methionine may be replaced with a substitute having the same or similar antioxidant effect. In some embodiments, methionine may be replaced with a substitute having the same antibody-protective effect. In some embodiments, methionine may be replaced with a substitute having the same or similar protein-stabilizing effect. In some embodiments, methionine may be replaced with a substitute having the same or similar ability to reduce antibody aggregation, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for histidine and / or methionine may be any of those provided herein, e.g., arginine or glycine, or any others known in the art. In some embodiments, NaCl may be replaced with another salt. In some embodiments, NaCl may be replaced with a substitute having the same or similar water solubility. In some embodiments, NaCl may be replaced with a substitute having the same or similar effect on the formulation isotonicity. In some embodiments, NaCl may be replaced with a substitute having the same or similar protein stabilizing effect, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for NaCl may be any of those provided herein, for example, other chloride salts, other sodium salts, ascorbic acid salts, acetate salts, phosphate salts, citrate salts, Tris salts, or succinates, or any others known in the art.

[0222] In some embodiments, polysorbate may be replaced with another surfactant and / or detergent. In some embodiments, polysorbate may be replaced with a substitute having the same or similar surfactant ability / effect. In some embodiments, polysorbate may be replaced with a substitute having the same or similar ability to solubilize antibodies and / or other excipients. In some embodiments, polysorbate may be replaced with a substitute having the same or similar ability to reduce antibody aggregation. In some embodiments, polysorbate may be replaced with a substitute having the same or similar protein stabilizing effect, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for polysorbate may be any of those provided herein, e.g., poloxamer 188, or any others known in the art. In some embodiments, the pH may be acidic. In some embodiments, the pH may be basic. In some embodiments, the pH may be modified. In some embodiments, the pH may be increased or decreased to match the characteristics of the components, excipients, and / or buffers used in the formulation and the antibody species used, and / or the amounts of the antibody, component, or excipient used. In some embodiments, the pH may be increased or decreased to the desired pH after the addition of the antibody, component, or excipient. Substitutes envisioned herein may be one or more of the excipients, diluents, salts, and buffers provided throughout this disclosure. In some embodiments, the antibody may be a VL sequence, VH sequence, VL / VH pair, and / or VL sequence from the heavy and light chain sequences depicted in Figure 18. L -CDR1, V L -CDR2, V L -CDR3, V H -CDR1, V H -CDR2, V H- Containing one or more sequences that have 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 with any set of CDR3s (which include one or more 1, 2, 3, 4, or 5 amino acid substitutions in any one of these CDRs).

[0223] For any embodiment of a sterile vial containing a pharmaceutical antibody preparation provided herein, histidine is L-histidine, D-histidine, or racemic histidine. For any embodiment of a pharmaceutical antibody preparation provided herein, histidine is racemic histidine. For any embodiment of a pharmaceutical antibody preparation provided herein, histidine is D-histidine. In some embodiments, histidine may be replaced with an alternative buffer having an appropriate pKa. In some embodiments, histidine may be replaced with a substitute having the same buffering capacity. In some embodiments, histidine may be replaced with another amino acid. In some embodiments, histidine may be replaced with a substitute exhibiting the same or similar antibody-protective effect. In some embodiments, histidine may be replaced with a substitute exhibiting the same or similar ability to reduce antibody aggregation. In some embodiments, histidine may be replaced with a substitute having the same or similar cryoprotective capacity, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for histidine may be any of those provided herein, such as arginine or glycine, or any other known in the art.

[0224] For any embodiment of a sterile vial containing a pharmaceutical antibody preparation provided herein, histidine is present at 10–50 mM, e.g., 10, 15, 20, 25, 30, 35, 40, 45, or 50 mM. In some embodiments, histidine is present at 20 mM or about 20 mM. In some embodiments where histidine is L-histidine, L-histidine is present at 10–50 mM, e.g., 10, 15, 20, 25, 30, 35, 40, 45, or 50 mM. In some embodiments where histidine is L-histidine, L-histidine is present at 20 mM or about 20 mM.

[0225] For any embodiment of the sterile vial containing the pharmaceutical antibody preparation provided herein, methionine is L-methionine. For any embodiment of the pharmaceutical antibody preparation provided herein, methionine is racemic methionine. For any embodiment of the pharmaceutical antibody preparation provided herein, methionine is D-methionine. In some embodiments, methionine may be replaced with an alternative buffer having an appropriate pKa. In some embodiments, methionine may be replaced with an alternative having the same buffering capacity. In some embodiments, methionine may be replaced with another amino acid. In some embodiments, methionine may be replaced with an alternative having the same or similar antioxidant effect. In some embodiments, methionine may be replaced with an alternative having the same antibody-protective effect. In some embodiments, methionine may be replaced with an alternative having the same or similar protein-stabilizing effect. In some embodiments, methionine may be replaced with an alternative having the same or similar ability to reduce antibody aggregation, including alternatives that may exhibit one or more of the properties provided herein. Substitutes for methionine may be any of those provided herein, such as arginine or glycine, or any other known in the art.

[0226] For any of the embodiments of sterile vials containing the pharmaceutical antibody preparations provided herein, methionine is present at 2–10 mM, for example, 2, 3, 4, 5, 6, 7, 8, 9, or 10 mM. In some embodiments, methionine is present at 5 mM or about 5 mM.

[0227] For any of the embodiments of sterile vials containing pharmaceutical antibody preparations provided herein, NaCl is present at 50–150 mM, for example, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 mM. In some embodiments, NaCl is present at 100 mM. In some embodiments, NaCl is present at a different concentration. It can be replaced with a salt. In some embodiments, NaCl can be replaced with a substitute having the same or similar water solubility. In some embodiments, NaCl can be replaced with a substitute having the same or similar effect on the isotonicity of the formulation. In some embodiments, NaCl can be replaced with a substitute having the same or similar protein stabilizing effect, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for NaCl may be any of those provided herein, for example, other chloride salts, other sodium salts, ascorbic acid salts, acetate salts, phosphates, citrates, Tris salts, or succinates, or any others known in the art.

[0228] For any embodiment of a sterile vial containing a pharmaceutical antibody preparation provided herein, the polysorbate comprises polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or any combination thereof. In some embodiments, the polysorbate comprises, essentially consists of, or comprises polysorbate 80. In some embodiments, the polysorbate is present in an amount of 0.01% to 0.04%, for example, 0.01%, 0.02%, 0.03%, or 0.04%. In some embodiments, the polysorbate is present in an amount of about 0.01% to about 0.04%, for example, about 0.01%, about 0.02%, about 0.03%, or about 0.04%. In some embodiments, the polysorbate is present in an amount of 0.02% or about 0.02%. In some embodiments where polysorbate is polysorbate 80, polysorbate 80 is present in an amount of 0.01% to 0.04%, for example, 0.01%, 0.02%, 0.03%, or 0.04%. In some embodiments where polysorbate is polysorbate 80, polysorbate 80 is present in an amount of about 0.01% to about 0.04%, for example, about 0.01%, about 0.02%, about 0.03%, or about 0.04%. In some embodiments, polysorbate 80 is present in an amount of 0.02% or about 0.02%. In some embodiments, polysorbate may be replaced with another surfactant and / or detergent. In some embodiments, polysorbate may be replaced with a substitute having the same or similar surfactant ability / effect. In some embodiments, polysorbate may be replaced with a substitute having the same or similar ability to solubilize antibodies and / or other excipients. In some embodiments, polysorbate may be replaced with a substitute having the same or similar ability to reduce antibody aggregation. In some embodiments, polysorbate may be replaced with a substitute having the same or similar protein stabilization effect, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for polysorbate may be any of those provided herein, e.g., poloxamer 188, or any others known in the art.

[0229] For any embodiment of a sterile vial containing a pharmaceutical antibody preparation provided herein, the pH is approximately 5.8. In some embodiments, the pH is 5.8. In some embodiments, the pH may be acidic. In some embodiments, the pH may be basic. In some embodiments, the pH may be modified. In some embodiments, the pH may be increased or decreased to match the characteristics of the components, excipients, and / or buffers used in the preparation, as well as the antibody species used, and / or the amounts of the antibody, component, or excipient used. In some embodiments, the pH may be increased or decreased to a desired pH after the addition of the antibody, component, or excipient.

[0230] For any embodiment of a sterile vial containing a pharmaceutical antibody preparation provided herein, the preparation further comprises one or more sugars or one or more sugar alcohols, or both, comprising one of any sugar or sugar alcohol disclosed herein or otherwise known in the art. In some embodiments, one or more sugars include sucrose. In some embodiments, one or more sugar alcohols include mannitol. In its formulation, the formulation comprises sucrose or mannitol, or both. In some embodiments, the formulation comprises sucrose and mannitol. In some embodiments, sucrose and / or mannitol may be replaced with another sugar and / or sugar alcohol. In some embodiments, sucrose and / or mannitol may be replaced with a substitute having the same or similar antibody-protective effect. In some embodiments, sucrose and / or mannitol may be replaced with a substitute exhibiting the same or similar ability to reduce antibody aggregation. In some embodiments, sucrose and / or mannitol may be replaced with a substitute having the same or similar cryoprotective ability. In some embodiments, sucrose and / or mannitol may be replaced with a substitute having the same effect on isotonicity, including substitutes that may exhibit one or more of the properties provided herein. Substitutes for sucrose and / or mannitol may be any of those provided herein, e.g., sorbitol, trehalose, dextrose, dextran, or dextran 40, or any others known in the art.

[0231] In some embodiments, one or more sugars or one or more sugar alcohols are present in amounts of 2% to 5%, for example, 2%, 3%, 4%, or 5%. In some embodiments, one or more sugars or one or more sugar alcohols are present in amounts of about 2% to about 5%, for example, about 2%, about 3%, about 4%, or about 5%. In some embodiments where the sugar is sucrose, sucrose is present in amounts of 2% to 5% or about 2% to 5%. In some embodiments where the sugar alcohol is mannitol, mannitol is present in amounts of 2% to 5% or about 2% to 5%.

[0232] For any embodiment of a sterile vial containing a pharmaceutical antibody preparation provided herein, the preparation is configured for parenteral administration. In some embodiments, the preparation is configured for subcutaneous administration. In some embodiments, the preparation configured for subcutaneous administration contains one or more sugars and / or one or more sugar alcohols. In some embodiments, the preparation configured for subcutaneous administration contains sucrose or mannitol, or both. In some embodiments, the preparation is configured for intravenous administration. In some embodiments, the preparation configured for intravenous administration does not contain one or more sugars and / or one or more sugar alcohols. In some embodiments, the preparation configured for intravenous administration does not contain sucrose or mannitol, or both.

[0233] In some embodiments, there is a sterile vial containing a therapeutically effective amount of an antibody, such as an anti-Gal3 antibody, as part of a pharmaceutical antibody preparation. In some embodiments, the sterile vial contains one of the pharmaceutical antibody preparations disclosed herein. In some embodiments, the pharmaceutical antibody preparation contains a therapeutically effective amount of an antibody. In some embodiments, the antibody is an anti-Gal3 antibody. In some embodiments, the antibody is one of the anti-Gal3 antibodies disclosed herein or otherwise known in the art, for example, as described in Patent Document 2. In some embodiments, the antibody has the sequence of SEQ ID NO: 31. H -V with sequence CDR1, sequence number 72 H -CDR2, V having sequence number 113 H -CDR3, V having sequence number 171 L -CDR1, V having sequence number 222 L V with sequence -CDR2; and sequence number 249 L -Contains CDR3. In some embodiments, the antibody is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the sequence of SEQ ID NO: 31. H-CDR1, for sequence number 72, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%; 95%, 96%, 97%, 98%, 99%, or 100% identical V H -CDR2, for the sequence of sequence number 113, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% 95%, 96%, 97%, 98%, 99%, or 100% identical V H -CDR3, for sequence number 171, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%; 95%, 96%, 97%, 98%, 99%, or 100% identical V L -CDR1, for sequence number 222, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%; 95%, 96%, 97%, 98%, 99%, or 100% identical V L -CDR2; and for the sequence of sequence number 249, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%; 95%, 96%, 97%, 98%, 99%, or 100% identical V L -Contains CDR3. In some embodiments, the antibody is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% similar to the sequence of SEQ ID NO: 31. H -CDR1, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to the sequence of sequence 72. V is 95%, 96%, 97%, 98%, 99%, or 100% similar. H-CDR2, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to sequence 113. V is 95%, 96%, 97%, 98%, 99%, or 100% similar. H -CDR3, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to sequence 171. V is 95%, 96%, 97%, 98%, 99%, or 100% similar. L -CDR1, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to sequence 222. V is 95%, 96%, 97%, 98%, 99%, or 100% similar. L -CDR2; and the sequence of sequence number 249 are at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94% similar to V. 95%, 96%, 97%, 98%, 99%, or 100% similar. L -Includes CDR3.

[0234] In some embodiments, the antibody has a sequence having at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to the sequence of SEQ ID NO: 31. H -CDR1, V has a sequence that has at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to the sequence of sequence number 72. H -CDR2, V has a sequence that has at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to the sequence of sequence number 113. H -CDR3, V has a sequence that has at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to the sequence of sequence number 171. L -CDR1, V has a sequence that has at least 0, 1, 2, 3, 4, 5, or 6 substitutions compared to the sequence of sequence number 222. L V has a sequence ...

Claims

1. A composition comprising an anti-Gal3 antibody or a conjugated fragment thereof for use in reducing or inhibiting inflammation in subjects where it is needed, The anti-Gal3 antibody or its conjugated fragment is (1) V Ｌ -CDR1, V Ｌ - CDR2 and V Ｌ - Light chain including a light chain variable region including CDR3, and (2) V Ｈ -CDR1, V Ｈ -CDR2 and V Ｈ - Includes a heavy chain containing a heavy chain variable region including CDR3, The foregoing V Ｌ -CDR1 includes an amino acid sequence containing SEQ ID NO: 171, and the foregoing V Ｌ -CDR2 includes an amino acid sequence containing SEQ ID NO: 222, and the foregoing V Ｌ -CDR3 includes an amino acid sequence containing SEQ ID NO: 249, and the foregoing V Ｈ -CDR1 includes an amino acid sequence containing SEQ ID NO: 31, and the foregoing V Ｈ -CDR2 includes an amino acid sequence containing SEQ ID NO: 72, and the foregoing V Ｈ -CDR3 includes an amino acid sequence containing SEQ ID NO: 113; or The aforementioned V Ｌ -CDR1 contains an amino acid sequence including sequence number 195, and the V Ｌ -CDR2 contains an amino acid sequence including sequence number 247, and the V Ｌ -CDR3 contains an amino acid sequence including sequence number 292, and the V Ｈ -CDR1 contains an amino acid sequence including SEQ ID NO: 39, and the V Ｈ -CDR2 contains the amino acid sequence including SEQ ID NO: 103 and the V Ｈ - Does CDR3 contain the amino acid sequence including SEQ ID NO: 165? The aforementioned V Ｌ -CDR1 contains an amino acid sequence including sequence number 216, and the V Ｌ -CDR2 contains an amino acid sequence including sequence number 230, and the V Ｌ -CDR3 contains an amino acid sequence including sequence number 267, and the V Ｈ -CDR1 contains an amino acid sequence including SEQ ID NO: 67, and the V Ｈ -CDR2 contains the amino acid sequence including SEQ ID NO: 82, and the V Ｈ - Does CDR3 contain the amino acid sequence that includes SEQ ID NO: 166? The aforementioned V Ｌ -CDR1 contains an amino acid sequence including sequence number 192, and the V Ｌ -CDR2 contains an amino acid sequence including sequence number 236, and the V Ｌ -CDR3 contains an amino acid sequence including sequence number 270, and the V Ｈ -CDR1 contains an amino acid sequence including sequence number 68, and the V Ｈ -CDR2 contains the amino acid sequence including SEQ ID NO: 82, and the V Ｈ - Does CDR3 contain the amino acid sequence including SEQ ID NO: 167? The aforementioned V Ｌ -CDR1 contains an amino acid sequence including sequence number 217, and the V Ｌ -CDR2 contains an amino acid sequence including sequence number 229, and the V Ｌ -CDR3 contains an amino acid sequence including sequence number 293, and the V Ｈ -CDR1 contains an amino acid sequence including SEQ ID NO: 69, and the V Ｈ -CDR2 contains the amino acid sequence including SEQ ID NO: 109 and the V Ｈ - Does CDR3 contain the amino acid sequence including SEQ ID NO: 168? The aforementioned V Ｌ -CDR1 contains an amino acid sequence including sequence number 218, and the V Ｌ -CDR2 contains an amino acid sequence including sequence number 237, and the V Ｌ -CDR3 contains an amino acid sequence including sequence number 294, and the V Ｈ -CDR1 contains an amino acid sequence including SEQ ID NO: 69, and the V Ｈ -CDR2 contains the amino acid sequence including SEQ ID NO: 109 and the V Ｈ - Does CDR3 contain the amino acid sequence including SEQ ID NO: 168? The aforementioned V Ｌ -CDR1 contains an amino acid sequence including sequence number 219, and the V Ｌ -CDR2 contains an amino acid sequence including sequence number 225, and the V Ｌ -CDR3 contains an amino acid sequence including sequence number 295, and the V Ｈ -CDR1 contains an amino acid sequence including SEQ ID NO: 70, and the V Ｈ -CDR2 contains the amino acid sequence including sequence number 110, and the V Ｈ - CDR3 contains the amino acid sequence containing SEQ ID NO: 169; or The aforementioned V Ｌ -CDR1 contains an amino acid sequence including sequence number 220, and the V Ｌ -CDR2 contains an amino acid sequence including sequence number 227, and the V Ｌ -CDR3 contains an amino acid sequence including sequence number 296, and the V Ｈ -CDR1 contains an amino acid sequence including sequence number 43, and the V Ｈ -CDR2 contains the amino acid sequence including sequence number 111, and the V Ｈ -CDR3 contains the amino acid sequence including SEQ ID NO: 138, A composition wherein administration of the anti-Gal3 antibody or its conjugated fragment reduces or inhibits neutrophil activation and / or migration in the subject, reduces or inhibits the cleavage of CD62L expressed by neutrophils, reduces or inhibits IL-8 production in the subject, reduces the number of neutrophils in the subject, and / or modulates the expression of myeloperoxidase (MPO), proliferation-associated oncogene α (GROα) / keratinocyte-derived chemokine (KC), Ly6c1, INOS, IL-6, TNFα, IL-1B, Col1A1, aSMA, TGFβ, VEGFA, VEGFB, or any combination thereof in the subject.

2. a. The inflammation in the subject is associated with neutrophil activation and / or migration; b. Administration of an effective amount of the anti-Gal3 antibody or its conjugated fragment reduces or inhibits neutrophil activation and / or migration in the subject; c. Administration of an effective amount of the anti-Gal3 antibody or its conjugated fragment reduces or inhibits the cleavage of CD62L expressed by neutrophils in the subject, and / or reduces or inhibits IL-8 production; d. Administration of an effective amount of the anti-Gal3 antibody or its conjugated fragment reduces the number of neutrophils in the subject; e. Administration of an effective amount of the anti-Gal3 antibody or its conjugated fragment modulates the expression of Gal3, myeloperoxidase (MPO), proliferation-associated oncogene α (GROα) / keratinocyte-derived chemokine (KC), Ly6c1, INOS, IL-6, TNFα, IL-1B, Col1A1, aSMA, TGFβ, VEGFA, VEGFB, or any combination thereof in the subject; f. Administration of an effective amount of the anti-Gal3 antibody or its conjugated fragment reduces the production of autoantibodies in the subject; g. Administration of an effective amount of the anti-Gal3 antibody or its conjugated fragment reduces the production of anti-nucleic acid autoantibodies in the subject; h. The inflammation includes pneumonia; i. The inflammation includes COPD, pneumonitis, asthma, sarcoidosis, pulmonary fibrosis, histiocytosis, bronchiolitis obliterans, or any combination thereof; j. The inflammation includes autoimmune diseases; k. The inflammation includes autoimmune diseases such as systemic lupus erythematosus (SLE), Graves' disease, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, celiac disease, or any combination thereof; l. The light chain variable region comprises an amino acid sequence having at least 90% identity with a sequence selected from sequence numbers 395 or 441-447; m. The light chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 395 or 441-447; n. The heavy chain variable region comprises an amino acid sequence having at least 90% identity with a sequence selected from SEQ ID NOs: 298 or 368-373; o. The heavy chain variable region comprises an amino acid sequence selected from SEQ ID NOs. 298 or 368-373; p. The anti-Gal3 antibody or its conjugated fragment comprises a light chain encoded by a nucleic acid sequence having at least 90% identity with a sequence selected from SEQ ID NOs. 622 or 696-702; q. The anti-Gal3 antibody or its conjugated fragment comprises a light chain encoded by a nucleic acid sequence selected from SEQ ID NOs. 622 or 696-702; r. The anti-Gal3 antibody or its conjugated fragment comprises a heavy chain encoded by a nucleic acid sequence having at least 90% identity with a sequence selected from SEQ ID NOs. 540 or 614-620; or s. The composition according to claim 1, wherein the anti-Gal3 antibody or its conjugated fragment comprises a heavy chain encoded by a nucleic acid sequence selected from SEQ ID NOs. 540 or 614-620.

3. histidine; Methionine; NaCl; and It also contains polysorbate, The pH is between 5.3 and 6.

3. The composition according to claim 1.

4. a. Further containing sucrose or mannitol, or both; b. The antibody is present in units of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg; c. The histidine is L-histidine; d. The L-histidine is present at a concentration of 10 to 50 mM; e. The L-histidine is present at 20 mM; f. The methionine is present at a concentration of 2 to 10 mM; g. The methionine is present at 5 mM; h. The NaCl is present at a concentration of 50 to 150 mM; i. The NaCl is present at a concentration of 100 mM; j. The polysorbate comprises polysorbate-20, polysorbate-40, polysorbate-60, polysorbate-80, or any combination thereof; k. The polysorbate comprises polysorbate-80; l. The polysorbate 80 is present in an amount of 0.01 to 0.04%; m. The polysorbate 80 is present at a concentration of 0.02%; n. The pH is 5.8; o. The sucrose is present in an amount of 2% to 5%; p. The aforementioned mannitol is present in a concentration of 2% to 5%; q. The antibody is present in an amount of 1 to 50 mg as a unit dose; r. The antibody is present in one of the following amounts as a unit dose: 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg, or in any amount within the range defined by any two of the above amounts; s. The antibody is present at one of the following concentrations: 1 mg / mL, 5 mg / mL, 10 mg / mL, 20 mg / mL, 40 mg / mL, or 50 mg / mL, or at any concentration within the range defined by any two of the above concentrations; t. The L-histidine is present at 20 mM, and the methionine is present at 5 mM, The solution contains 100 mM NaCl, 0.02% polysorbate 80, 2-5% sucrose, 2-5% mannitol, a pH of 5.8, and the therapeutically effective dose of the antibody is any amount within the range defined by one of 1 mg, 5 mg, 10 mg, 20 mg, 40 mg, or 50 mg as a unit dose, or any two of the above amounts; u. The sucrose is present in an amount of 2% to 5%, and the mannitol is present in an amount of 2% to 5%; v. Consists of being administered parenterally; w. It is designed for subcutaneous administration; x. The composition configured for subcutaneous administration comprises sucrose, mannitol, or both; y. Consists of being administered intravenously; z. The composition configured for intravenous administration does not contain sucrose, mannitol, or both; aa. Prepared at antibody concentrations of 20 mg / mL or 50 mg / mL; and / or The composition according to claim 3, which remains 60% stable for three months at either 5°C or 25°C / 60% relative humidity (RH).

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