Motile sperm domain-containing protein 2 antibody and its method of use

Abstract

The present disclosure relates to antibodies or antigen-binding fragments thereof that specifically bind to motile sperm domain-containing protein 2 (MOSPD2) and methods of use thereof.

Description

Cross-reference of related applications

[0001] This application claims priority and benefit to U.S. Provisional Patent Application No. 63 / 076,697 filed September 10, 2020, and U.S. Provisional Patent Application No. 63 / 167,317 filed March 29, 2021. The entire contents of those applications are incorporated herein by reference. Reference to electronically submitted sequence listings

[0002] The contents of the electronically submitted sequence listing in the ASCII text file (name: 3182_096PC 03_Seqlisting_ST 25.txt; size: 40,794 bytes; creation date: September 7, 2021) submitted with this application are incorporated herein by reference in their entirety. [Technical Field]

[0003] This disclosure relates to an antibody that specifically binds to motile sperm domain-containing protein 2 (MOSPD2), its antigen-binding fragment, and a method of using the same. [Background technology]

[0004] White blood cells are immune system cells involved in the body's defense against infections and foreign substances. Monocytes are a type of white blood cell that play a crucial role in innate and adaptive immunity, immune surveillance, and particle capture. A subset of monocytes is "resident," recruited to tissues independently of inflammatory stimuli to monitor steady state, aid in wound healing, and resolve inflammation, while the majority of human circulating monocytes (80-90%) are classified as "inflammatory." Circulating monocytes can sense inflammatory stimuli and rapidly migrate to the periphery via blood vessels or lymphatic endothelium, where they can differentiate into macrophages and dendritic cells (DCs) and work with further cell subsets to promote inflammation. While monocytes play an essential role in host defense, they have also been identified as important mediators of inflammatory damage.

[0005] Chemokine receptors and adhesion molecules play a crucial role in regulating leukocyte transport. A complex array of chemokine receptors and G protein-coupled receptors (GPCRs), differentially expressed in leukocyte lineages and subsets, controls which cell types migrate to which tissues under different conditions. Chemokines, or chemotactic cytokines, are secreted proteins that regulate the migration and activation of leukocytes and stromal cells. Binding of chemokines to chemokine receptors activates signaling pathways such as the MAPK / ERK and PI3K / AKT pathways, leading to phosphorylation of ERK and AKT, respectively. In the case of inflammatory monocytes, their migration across the endothelial cell monolayer from the bone marrow (extravasation), into the circulatory system (invasion), and into inflammatory tissues depends on CC motif receptor 2 (CCR2) signaling in response to activation by chemokine CC motif ligand (CCL) 2 (also known as monocyte chemotactic protein-1, MCP-1) and CCL7 (MCP-3). On the other hand, the constitutive migration of commensal monocytes to non-inflammatory tissues is primarily dependent on CCL3 (macrophage inflammatory protein-1α, also known as MIP-1α) and the chemokine (C-X3-C motif) ligand 1 (CX3CL1).

[0006] Inhibiting the migration of inflammatory cells to the site of inflammation (e.g., leukocyte chemotaxis) is an attractive anti-inflammatory approach for treating chronic diseases. Suppressing the undesirable accumulation of monocytes and / or macrophages in chronically inflammatory tissues has therapeutic potential, and therefore, migration inhibitors have demonstrated beneficial therapeutic outcomes in animal models and clinical trials. Nevertheless, there have been failures in several phase II clinical trials of chemokines and chemokine receptor antagonists, possibly due to the redundancy of target receptors and the complexity of heterogeneous diseases such as multiple sclerosis and rheumatoid arthritis.

[0007] Fibrosis is the formation of excessive fibrous connective tissue in an organ or tissue. Fibrosis is analogous to the process of scarring, both involving stimulating cells (e.g., fibroblasts) that lay connective tissue containing collagen and glycosaminoglycans. Fibrosis is a dynamic process that occurs in four stages: i) initiation due to organ / tissue injury, ii) inflammation and activation of effector cells, iii) enhancement of extracellular matrix (ECM) synthesis, and iv) deposition of ECM, leading to progression to terminal organ failure.

[0008] Fibrosis can cause severe morbidity and adverse effects on patients' daily functioning, activities of daily living (ADL), and quality of life, potentially leading to a poor prognosis. For example, idiopathic pulmonary fibrosis (IPF) is a refractory chronic disease characterized by worsening shortness of breath and debilitation. IPF patients become oxygen-dependent, with a median mean survival time of 3 years after diagnosis and a 5-year survival rate of 20% to 40%. Therefore, the development of new treatments for fibrosis is needed.

[0009] Metastasis, or the spread of cancer cells from their tissue of origin to other organs, is the result of a multi-step process involving numerous molecules. Evidence suggests that chemokines and chemokine receptors play a crucial role in tumor metastasis.

[0010] MOSPD2 is a highly conserved protein with a length of 518 amino acids, exhibiting 90% homology between humans and mice. Bioinformatics analysis shows that MOSPD2 contains a CRAL-TRIO region, named after the cellular retinal aldehyde-binding protein (CRALBP) and the TRIO protein. MOSPD2 also contains a region structurally related to the major spermatogenic protein of the nematode and one transmembrane region.

[0011] MOSPD2 is expressed on the surface of monocytes infiltrating inflammatory tissue and in various tumor types (International Publication No. 2017 / 021857). It is associated with cancer cell metastasis and promotes monocyte migration (International Publication No. 2017 / 021857). Therefore, MOSPD2 (e.g., using anti-MOSPD2 antibodies) is described as a treatment for inflammatory diseases and disorders (International Publication No. 2017 / 021855) as well as for cancer and cancer metastasis (International Publication No. 2017 / 021857). [Prior art documents] [Patent Documents]

[0012] [Patent Document 1] International Publication No. 2017 / 021857 Brochure [Patent Document 2] International Publication No. 2017 / 021855 Brochure [Overview of the project]

[0013] This specification provides an antibody or antigen-binding fragment that specifically binds to motile sperm domain-containing protein 2 (MOSPD2), and comprises the following: A heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having 80% or more identity with SEQ ID NO: 1; Heavy chain CDR2 containing one amino acid sequence from sequence numbers 2-8, or a sequence having 80% or more identity with one of sequence numbers 2-8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing one amino acid sequence from sequence numbers 10-18, or a sequence having 80% or more identity with one of sequence numbers 10-18; Light chain CDR2 containing one amino acid sequence from sequence numbers 19-24, or a sequence having 80% or more identity with one of sequence numbers 19-24; and A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having at least 80% identity with SEQ ID NO: 25.

[0014] In some embodiments, the antibody or antigen-binding fragment thereof comprises: A heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 1 or a sequence having at least 90% identity with SEQ ID NO: 1; A heavy chain CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 2-8 or a sequence having at least 90% identity with any one of SEQ ID NOs: 2-8; A heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 9; A light chain CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 10-18 or a sequence having at least 90% identity with any one of SEQ ID NOs: 10-18; A light chain CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 19-24 or a sequence having at least 90% identity with any one of SEQ ID NOs: 19-24; and A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having at least 90% identity with SEQ ID NO: 25.

[0015] In some embodiments, the antibody or antigen-binding fragment thereof comprises: A heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 1 or a sequence having at least 95% identity with SEQ ID NO: 1; A heavy chain CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 2-8 or a sequence having at least 95% identity with any one of SEQ ID NOs: 2-8; A heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 9; A light chain CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 10-18 or a sequence having at least 95% identity with any one of SEQ ID NOs: 10-18; A light chain CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 19-24 or a sequence having at least 95% identity with any one of SEQ ID NOs: 19-24; and A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having at least 95% identity with SEQ ID NO: 25.

[0016] In some embodiments, the antibody or its antigen-binding fragment includes: Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; A heavy chain CDR2 containing one of the amino acid sequences from sequence numbers 2-8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing one of the amino acid sequences from sequence numbers 10-18; Light chain CDR2 containing any one amino acid sequence from sequence numbers 19-24; and A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0017] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0018] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0019] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0020] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0021] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0022] In some embodiments, the antibody or antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0023] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0024] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0025] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0026] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0027] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0028] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 6; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0029] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 6; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 14; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 23; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0030] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0031] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 8; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0032] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0033] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 16; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0034] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0035] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 18; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0036] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0037] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0038] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR7 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0039] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR7 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0040] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR7 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0041] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR7 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0042] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR7 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0043] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR7 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0044] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR7 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0045] In some embodiments, the antibody or its antigen-binding fragment comprises a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR7 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0046] This specification provides an antibody or antigen-binding fragment that specifically binds to MOSPD2, and comprises the following: A heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence having one or more conservative substitutions in SEQ ID NOs: 2-8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; Light chain CDR1 containing one amino acid sequence from sequence numbers 10-18, or a sequence having one or more conservative substitutions in one of sequence numbers 10-18; Light chain CDR2 containing any one amino acid sequence from SEQ ID NOs. 19-24, or a sequence having one or more conserved amino acid substitutions in any one of SEQ ID NOs. 19-24; and A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0047] In some embodiments, the antibody or its antigen-binding fragment is a polyclonal antibody, a monoclonal antibody, a mouse antibody, a human antibody, a humanized antibody, or a chimeric antibody.

[0048] In some embodiments, the antibody or its antigen-binding fragment is a Fab, Fab', F(ab')2, Fv, scFv, sdFv fragment, VH domain, VL domain, or a combination thereof.

[0049] In some embodiments, the antibody or its antigen-binding fragment is IgG1, IgG2, IgG3, IgG4, its variants, or a combination thereof.

[0050] In some embodiments, approximately 1 × 10 5 (1 / Ms) ~ approx. 7×10 6 The value of Ka (1 / Ms); approximately 1 × 10⁻⁶ -4 (1 / s) ~ a Kd value of approximately 0.4(1 / s); and / or approximately 2 × 10 -10 (M)~Approx. 6×10 -8 (M) is bound to MOSPD2 with the calculated KD.

[0051] In some embodiments, MOSPD2 is human MOSPD2. In some embodiments, MOSPD2 has one amino acid sequence of any one of sequence numbers 26-29. In some embodiments, MOSPD2 has an amino acid sequence encoded by one of sequence numbers 30-33.

[0052] Nucleic acids encoding antibodies or antigen-binding fragments thereof are provided herein.

[0053] A vector comprising nucleic acid encoding an antibody or an antigen-binding fragment thereof is provided herein.

[0054] Cells comprising a vector containing a nucleic acid encoding an antibody or an antigen-binding fragment thereof are provided herein.

[0055] A method for producing an antibody or antigen-binding fragment that specifically binds to MOSPD2 is provided herein, comprising culturing cells containing a vector comprising a nucleic acid encoding the antibody or antigen-binding fragment described herein under appropriate conditions, and isolating the antibody or antigen-binding fragment.

[0056] A composition comprising an antibody or antigen-binding fragment thereof as described herein, a nucleic acid encoding the antibody or antigen-binding fragment thereof as described herein, a vector comprising the nucleic acid encoding the antibody or antigen-binding fragment thereof as described herein, or a cell comprising the vector comprising the nucleic acid encoding the antibody or antigen-binding fragment thereof as described herein, and a carrier is provided herein.

[0057] This specification provides a kit comprising an antibody or its antigen-binding fragment as described herein, a nucleic acid encoding the antibody or its antigen-binding fragment as described herein, a vector containing the antibody or its antigen-binding fragment as described herein, or a vector containing the antibody or its antigen-binding fragment as described herein, and instructions for use.

[0058] A method for treating or preventing an inflammatory disease or disorder is provided herein, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof.

[0059] A method for inhibiting or preventing the migration of inflammatory cells is provided herein, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, the inflammatory cells are monocytes or neutrophils.

[0060] A method for treating or preventing non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) is provided herein, comprising administering a therapeutically effective amount of the antibody or antigen-binding fragment described herein to a subject in need thereof.

[0061] Methods for treating or preventing fibrosis are provided herein, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, the fibrosis is hepatic fibrosis.

[0062] Methods for treating or preventing arthritis are provided herein, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, the arthritis is rheumatoid arthritis or psoriatic arthritis. In some embodiments, the method further comprises administering a further therapeutic agent to the subject. In some embodiments, the further therapeutic agent is methotrexate, baricitinib, hydroxychloroquine, prednisone, etanercept, sulfasalazine, infliximab, adalimumab, ixekizumab, or a combination thereof.

[0063] Methods for treating or preventing multiple sclerosis are provided herein, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, multiple sclerosis is relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, or secondary progressive multiple sclerosis. In some embodiments, the method further comprises administering a further therapeutic agent to the subject. In some embodiments, the further therapeutic agent is teriflunomide, natalizumab, dimethyl fumarate, ocrelizumab, IFNβ-1a, cladribine, glatiramer acetate, or a combination thereof.

[0064] Methods for treating or preventing inflammatory bowel disease are provided herein, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, the inflammatory bowel disease is ulcerative colitis or Crohn's disease. In some embodiments, the method further comprises administering a further therapeutic agent to the subject. In some embodiments, the further therapeutic agent is infliximab, vedolizumab, azathioprine, adalimumab, masalazine, or a combination thereof.

[0065] A method for treating or preventing cancer metastasis is provided herein, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof.

[0066] A method for treating or preventing cancer is provided herein, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof.

[0067] In some aspects, cancer is breast cancer, cervical cancer, melanoma, bone marrow cancer, colon cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, thyroid cancer, or prostate cancer.

[0068] In some embodiments, the antibody or its antigen-binding fragment is administered intravenously or subcutaneously to the subject. In some cases, the subject is a human being. [Invention 1001] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having 80% or more identity with SEQ ID NO: 1; Heavy chain CDR2 containing one amino acid sequence from sequence numbers 2-8, or a sequence having 80% or more identity to one of sequence numbers 2-8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing one amino acid sequence from sequence numbers 10-18, or a sequence having 80% or more identity with one of sequence numbers 10-18; Light chain CDR2 containing one amino acid sequence from sequence numbers 19-24, or a sequence having 80% or more identity with one of sequence numbers 19-24; and An antibody or its antigen-binding fragment that specifically binds to motile sperm domain-containing protein 2 (MOSPD2), comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25 or a sequence having 80% or more identity with SEQ ID NO: 25. [Invention 1002] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having 90% or more identity with SEQ ID NO: 1; Heavy chain CDR2 containing one amino acid sequence from sequence numbers 2-8, or a sequence having 90% or more identity with one of sequence numbers 2-8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing one amino acid sequence from sequence numbers 10-18, or a sequence having 90% or more identity with one of sequence numbers 10-18; Light chain CDR2 containing one amino acid sequence from sequence numbers 19-24, or a sequence having 90% or more identity with one of sequence numbers 19-24; and An antibody according to the present invention 1001 or an antigen-binding fragment thereof, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25 or a sequence having 90% or more identity with SEQ ID NO: 25. [Invention 1003] A heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having 95% or more identity with SEQ ID NO: 1; Heavy chain CDR2 containing one amino acid sequence from sequence numbers 2-8, or a sequence having 95% or more identity with one of sequence numbers 2-8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing one amino acid sequence from sequence numbers 10-18, or a sequence having 95% or more identity with one of sequence numbers 10-18; Light chain CDR2 containing one amino acid sequence from sequence numbers 19-24, or a sequence having 95% or more identity with one of sequence numbers 19-24; and An antibody or antigen-binding fragment of the present invention 1001 or 1002, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25 or a sequence having 95% or more identity with SEQ ID NO: 25. [Invention 1004] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; A heavy chain CDR2 containing one of the amino acid sequences from sequence numbers 2-8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing one of the amino acid sequences from sequence numbers 10-18; Light chain CDR2 containing one of the amino acid sequences from sequence numbers 19-24; An antibody or antigen-binding fragment of any of the present invention 1001 to 1003, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1005] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1006] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1007] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1008] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1009] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1010] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1011] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1012] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1013] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1014] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1015] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1016] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 6; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1017] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 6; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 14; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 23; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1018] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1019] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1020] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1021] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 16; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1022] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1023] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 18; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1024] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1025] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1026] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1027] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1028] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1029] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1030] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1031] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1032] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1033] Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and An antibody or antigen-binding fragment of any of the present invention 1001 to 1004, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25. [Invention 1034] A heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence having one or more conservative substitutions in SEQ ID NOs: 2-8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; Light chain CDR1 containing one amino acid sequence from sequence numbers 10-18, or a sequence having one or more conservative substitutions in one of sequence numbers 10-18; Light chain CDR2 containing any one amino acid sequence from SEQ ID NOs. 19-24, or a sequence having one or more conserved amino acid substitutions in any one of SEQ ID NOs. 19-24; and An antibody or its antigen-binding fragment that specifically binds to MOSPD2, comprising a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25. [Invention 1035] An antibody or antigen-binding fragment thereof according to any of the present invention 1001 to 1034, wherein the antibody is a polyclonal antibody, a monoclonal antibody, a mouse antibody, a human antibody, a humanized antibody, or a chimeric antibody. [Invention 1036] An antibody or its antigen-binding fragment according to any of the Invention 1001 to 1035, wherein the antigen-binding fragment is Fab, Fab', F(ab')2, Fv, scFv, sdFv fragment, VH domain, VL domain, or a combination thereof. [Invention 1037] The antibody or antigen-binding fragment thereof according to any of the present invention 1001 to 1036, wherein the antibody is IgG1, IgG2, IgG3, IgG4, a variant thereof, or a combination thereof. [Invention 1038] Approximately 1×10 5 (1 / Ms) ~ approx. 7×10 6 The value of Ka (1 / Ms); approximately 1 × 10⁻⁶ -4 (1 / s) ~ a Kd value of approximately 0.4(1 / s); and / or approximately 2 × 10 -10 (M)~Approx. 6×10 -8 An antibody or antigen-binding fragment of any of the Invention 1001-1037 that binds to MOSPD2 with the calculated KD of (M). [Invention 1039] An antibody or antigen-binding fragment of any of the present invention 1001 to 1038, wherein the MOSPD2 is human MOSPD2. [Invention 1040] The MOSPD2 has one of the amino acid sequences from sequence numbers 26 to 29, wherein the antibody or antigen-binding fragment of any of the present invention 1001 to 1039 is wherein the MOSPD2 has one of the amino acid sequences from sequence numbers 26 to 29. [Invention 1041] The MOSPD2 has an amino acid sequence encoded by one of the nucleic acid sequences of sequence numbers 30 to 33, wherein the antibody or antigen-binding fragment of any of the present invention 1001 to 1040 is wherein the MOSPD2 has an amino acid sequence encoded by any one of the nucleic acid sequences of sequence numbers 30 to 33. [Invention 1042] A nucleic acid encoding any antibody or antigen-binding fragment thereof according to invention 1001 to 1041. [Invention 1043] A vector containing nucleic acid according to the present invention 1042. [Invention 1044] Cells containing the vector of the present invention 1043. [Invention 1045] A method for producing an antibody or antigen-binding fragment that specifically binds to MOSPD2, comprising culturing cells of the present invention 1044 under suitable conditions and isolating the antibody or antigen-binding fragment. [Invention 1046] A composition comprising an antibody or antigen-binding fragment of any of the present inventions 1001 to 1041, a nucleic acid of the present invention 1042, a vector of the present invention 1043, or a cell of the present invention 1044, and a carrier. [Invention 1047] A kit comprising an antibody or antigen-binding fragment of any of Invention 1001 to 1041, a nucleic acid of Invention 1042, a vector of Invention 1043, or cells of Invention 1044, and instructions for use. [Invention 1048] A method for treating or preventing an inflammatory disease or disorder, comprising administering a therapeutically effective amount of any antibody or antigen-binding fragment of the present invention 1001 to 1041 to a subject in need thereof. [Invention 1049] A method for inhibiting or preventing the migration of inflammatory cells, comprising administering a therapeutically effective amount of any antibody or antigen-binding fragment according to Invention 1001 to 1041 to a subject in need thereof. [Invention 1050] The method of the present invention 1049, wherein the inflammatory cells are monocytes or neutrophils. [Invention 1051] A method for treating or preventing non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), comprising administering a therapeutically effective amount of any antibody or antigen-binding fragment of the present invention 1001 to 1041 to a subject in need thereof. [Invention 1052] A method for treating or preventing fibrosis, comprising administering a therapeutically effective amount of any antibody or antigen-binding fragment of the present invention 1001 to 1041 to a subject in need thereof. [Invention 1053] The method of the present invention 1052, wherein the fibrosis is hepatic fibrosis. [Invention 1054] A method for treating or preventing arthritis, comprising administering a therapeutically effective amount of any antibody or antigen-binding fragment of the present invention 1001 to 1041 to a subject in need thereof. [Invention 1055] The method of the present invention 1054, wherein the arthritis is rheumatoid arthritis or psoriatic arthritis. [Invention 1056] The method of the present invention 1054 or 1055, further comprising administering a further therapeutic agent to the subject. [Invention 1057] The method of the present invention 1056, wherein the further therapeutic agent is methotrexate, baricitinib, hydroxychloroquine, prednisone, etanercept, sulfasalazine, infliximab, adalimumab, ixekizumab, or a combination thereof. [Invention 1058] A method for treating or preventing multiple sclerosis, comprising administering a therapeutically effective amount of any antibody or antigen-binding fragment according to items 1001 to 1041 of the present invention to a subject in need thereof. [Invention 1059] The method of the present invention 1058, wherein the multiple sclerosis is relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, or secondary progressive multiple sclerosis. [Invention 1060] The method of the present invention 1058 or 1059, further comprising administering a further therapeutic agent to the subject. [Invention 1061] The method of the present invention 1060, wherein the further therapeutic agent is teriflunomide, natalizumab, dimethyl fumarate, ocrelizumab, IFNβ-1a, cladribine, glatiramer acetate, or a combination thereof. [Invention 1062] A method for treating or preventing inflammatory bowel disease, comprising administering a therapeutically effective amount of any antibody or antigen-binding fragment of the present invention 1001 to 1041 to a subject in need thereof. [Invention 1063] The method of the present invention 1062, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [Invention 1064] The method of the present invention 1063, further comprising administering a further therapeutic agent to the subject. [Invention 1065] The method of the present invention 1064, wherein the further therapeutic agent is infliximab, vedolizumab, azathioprine, adalimumab, masalazine, or a combination thereof. [Invention 1066] A method for treating or preventing cancer metastasis, comprising administering a therapeutically effective amount of any antibody or antigen-binding fragment according to Invention 1001 to 1041 to a subject in need thereof. [Invention 1067] A method for treating or preventing cancer, comprising administering a therapeutically effective amount of any antibody or antigen-binding fragment according to Invention 1001 to 1041 to a subject in need thereof. [Invention 1068] The method of the present invention 1066 or 1067, wherein the cancer is breast cancer, cervical cancer, melanoma, bone marrow cancer, colon cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, thyroid cancer, or prostate cancer. [Invention 1069] A method of the present invention, comprising intravenously administering the antibody or its antigen-binding fragment to the subject. [Invention 1070] A method of the present invention, comprising subcutaneously administering the antibody or its antigen-binding fragment to the subject.

Brief Description of the Drawings

[0069] Some aspects of the present invention are described herein by way of example only with reference to the accompanying drawings. Referring particularly to the drawings in detail, it is emphasized that the details shown are by way of example and for purposes of illustrative description of aspects of the present invention only. [Figure 1] Flow cytometry analysis of the surface expression of MOSPD2 in human monocytes is shown. [Figure 2] Sensorgram plots of the binding of anti-MOSPD2 antibodies at 1-16 nM to human MOSPD2 are shown. [Figure 3A] Dose-response inhibition of monocyte migration by increasing doses of anti-MOSPD2 antibodies is shown. The results shown are the mean ± standard deviation of three experiments. *p<0.001 [Figure 3B] Calculation of EC50 based on the results of Example 4 is shown. [Figure 4A] Some anti-MOSPD2 antibody variants that significantly inhibit monocyte migration are shown. [Figure 4B] Some anti-MOSPD2 antibody variants that significantly inhibit monocyte migration are shown. [Figure 4C] Some anti-MOSPD2 antibody variants that significantly inhibit monocyte migration are shown. [Figure 4D] Some anti-MOSPD2 antibody variants that significantly inhibit monocyte migration are shown. [Figure 4E] Some anti-MOSPD2 antibody variants that significantly inhibit monocyte migration are shown. [Figure 4F] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4G] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4H] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4I] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4J] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4K] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4L] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4M] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4N] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4O] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4P] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4Q] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4R] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4S] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4T] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4U] This study shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4V]Shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4W] Shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4X] Shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4Y] Shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4Z] Shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4AA] Shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. [Figure 4BB] Shows several anti-MOSPD2 antibody variants that significantly inhibit monocyte migration. The results shown are the mean ± standard deviation of three experiments. *p<0.05, **p<0.01, ***p<0.001. [Figure 5] Shows liver histology and the development of fibrosis after induction of NASH by HFHC diet and after treatment with control antibody (control Ab) or anti-MOSPD2 antibody. Results of two staining protocols, H&E and Masson trichrome, are shown, representing 10 - 11 animals tested. [Figure 6A] Shows staining of CD68+ cells in liver samples of mice fed control diet (CHOW diet) or HFHC diet after treatment with control antibody (isotype control) or anti-MOSPD2 antibody. [Figure 6B] Shows staining of CD68+ cells in liver samples of mice fed control diet (CHOW diet) or HFHC diet after treatment with control antibody (isotype control) or anti-MOSPD2 antibody. [Figure 6C] Shows staining of CD68+ cells in liver samples of mice fed control diet (CHOW diet) or HFHC diet after treatment with control antibody (isotype control) or anti-MOSPD2 antibody. [Figure 6D]The quantification of the fibrotic regions in these samples is shown. *p<0.05, **p<0.01. [Figure 7] This study demonstrates the effect of anti-MOSPD2 antibody treatment on disease activity in a mouse model of trinitrobenzenesulfonic acid (TNBS)-induced colitis. *p<0.05, **p≦0.005, ***p≦0.001. The results shown are from 15 animals. [Figure 8A] This study demonstrates the effects of anti-MOSPD2 antibody treatment on IL-6, MCP-1, and IL-12p40 levels in a mouse model of TNBS-induced colitis. [Figure 8B] This study demonstrates the effects of anti-MOSPD2 antibody treatment on IL-6, MCP-1, and IL-12p40 levels in a mouse model of TNBS-induced colitis. [Figure 8C] This study demonstrates the effects of anti-MOSPD2 antibody treatment on IL-6, MCP-1, and IL-12p40 levels in a mouse model of TNBS-induced colitis. *p<0.05. [Figure 9] This study demonstrates that treatment with an anti-MOSPD2 antibody significantly inhibits monocyte migration from patients with relapsing-remitting multiple sclerosis (RRMS). The results are from 7 out of 25 patients with different activation therapies and disease severities. **p<0.01, ***p<0.001. [Figure 10] Treatment with anti-MOSPD2 antibodies significantly inhibits monocyte migration from patients with primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS). The results are from 7 out of 25 patients with different activation therapies and disease severities. *p<0.05, **p<0.01, ***p<0.001. [Figure 11] Treatment with anti-MOSPD2 antibodies significantly inhibits monocyte migration from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). *p<0.05, **p<0.01, ***p<0.001. [Figure 12]This study demonstrates that treatment with anti-MOSPD2 antibodies significantly inhibits monocyte migration from patients with Crohn's disease and ulcerative colitis. *p<0.05, **p<0.01, ***p<0.001. [Figure 13A] This paper presents flow cytometry analysis of MOSPD2 surface expression in different human cancer cell lines. [Figure 13B] This paper presents flow cytometry analysis of MOSPD2 surface expression in different human cancer cell lines. [Figure 13C] This paper presents flow cytometry analysis of MOSPD2 surface expression in different human cancer cell lines. [Figure 13D] This paper presents flow cytometry analysis of MOSPD2 surface expression in different human cancer cell lines. [Modes for carrying out the invention]

[0070] To make this disclosure more easily understandable, certain terms are defined first. Where used in this Application, each of the following terms shall have the meanings set forth below, unless otherwise expressly presented herein. Further definitions are provided throughout this Application. definition

[0071] Various terms relating to the nature of disclosure are used throughout this specification and the claims. Unless otherwise indicated, such terms should be given their ordinary meanings in the art. Other specifically defined terms should be interpreted in a manner consistent with the definitions presented herein.

[0072] The term “antibody” means an immunoglobulin molecule that recognizes and specifically binds to a target such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or a combination of the aforementioned via at least one antigen recognition site within the variable region of the immunoglobulin molecule. As used herein, the term “antibody” encompasses intact polyclonal antibodies, intact monoclonal antibodies, chimeric antibodies, humanized antibodies, human antibodies, antibody-containing fusion proteins, and any other modified immunoglobulin molecule insofar as the antibody exhibits the desired biological activity. Antibodies may be one of the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or their subclasses (isotypes) (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), based on the identity of their heavy chain constant domains, which are called alpha, delta, epsilon, gamma, and mu, respectively. Different classes of immunoglobulins have different known subunit structures and three-dimensional configurations. Antibodies may be in their plain form or conjugated with other molecules such as toxins or radioisotopes.

[0073] Unless otherwise explicitly stated, and unless the context indicates otherwise, the term “antibody” includes monospecific, bispecific, or multispecific antibodies, as well as single-chain antibodies.

[0074] An "antigen-binding fragment" refers to a portion of an intact antibody that binds to an antigen. An antigen-binding fragment may include the antigen-recognition site of the intact antibody (e.g., a complementarity-determining region (CDR) sufficient to specifically bind to the antigen). Examples of antibody antigen-binding fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments, linear antibodies, and single-chain antibodies. Antibody antigen-binding fragments may originate from any animal species, such as rodents (e.g., mice, rats, or hamsters) and humans, or they may be artificially produced.

[0075] A “monoclonal” antibody or its antigen-binding fragment refers to a homogeneous population of antibodies or antigen-binding fragments involved in highly specific binding to a single antigenic determinant or epitope. This is in contrast to polyclonal antibodies, which typically contain different antibodies directed toward different antigenic determinants. The term “monoclonal” antibody or its antigen-binding fragment encompasses both intact and full-length monoclonal antibodies, as well as antibody fragments (e.g., Fab, Fab', F(ab')2, Fv), single-chain (scFv) variants, fusion proteins containing antibody moieties, and any other modified immunoglobulin molecules containing antigen recognition sites. Furthermore, “monoclonal” antibodies or their antigen-binding fragments refer to such antibodies and their antigen-binding fragments produced by any number of methods, including but not limited to hybridomas, phage selection, recombinant expression, and transgenic animals.

[0076] The term “humanized” antibody or antigen-binding fragment refers to a form of non-human (e.g., mouse) antibody or antigen-binding fragment that is a specific immunoglobulin chain, chimeric immunoglobulin, or fragment thereof containing the smallest non-human (e.g., mouse) sequence. Typically, a humanized antibody or antigen-binding fragment is a human immunoglobulin in which residues from the complementarity-determining region (CDR) are replaced with residues from the CDR of a non-human species (e.g., mouse, rat, rabbit, hamster) that has the desired specificity, affinity, and capability ("CDR grafting") (Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239:1534-1536 (1988)). In some cases, residues in specific Fv framework regions (FRs) of human immunoglobulins are replaced with corresponding residues of non-human species-derived antibodies or fragments that have the desired specificity, affinity, and capability. Humanized antibodies or their antigen-binding fragments can be further modified by substitution of additional residues in the Fv framework region and / or non-human CDR residues to improve and optimize the specificity, affinity, and / or capability of the antibody or its antigen-binding fragment. Generally, humanized antibodies or their antigen-binding fragments contain a variable domain that includes all or substantially all of the CDR region corresponding to the non-human immunoglobulin, and all or substantially all of the FR region is from the human immunoglobulin consensus sequence. Humanized antibodies or their antigen-binding fragments may also contain at least some immunoglobulin constant regions or domains (Fc), typically those of human immunoglobulin. Examples of methods used to produce humanized antibodies are described in U.S. Patent No. 5,225,539; Roguska et al., Proc. Natl. Acad. Sci., USA, 91(3):969-73 (1994), and Roguska et al., Protein Eng. 9(10):895-904 (1996).

[0077] The term "human" antibody or antigen-binding fragment means an antibody or antigen-binding fragment having an amino acid sequence derived from a human immunoglobulin locus, and such antibody or antigen-binding fragment is prepared using any technique known in the art. This definition of human antibody or antigen-binding fragment includes intact or full-length antibodies and their fragments.

[0078] As used herein, the term “treating” includes inhibiting, blocking, slowing or reversing the progression of a condition, substantially improving the clinical or aesthetic symptoms of a condition, or substantially preventing the appearance of clinical or aesthetic symptoms of a condition.

[0079] As used herein, terms such as “administer,” “give delivery,” and “dosage” refer to methods that can be used to enable the delivery of an antibody or its antigen-binding fragment to a desired site of action (e.g., intravenous administration). Dosage techniques that can be used with the agents and methods described herein can be found, for example, in Goodman and Gilman, The Pharmacological Basis of Therapeutics, current edition, Pergamon; and Remington's, Pharmaceutical Sciences, current edition, Mack Publishing Co., Easton, Pa. and Matucci, A. et al., Respiratory Research, 19(1):154 (2018).

[0080] The terms “subject” and “patient” are used interchangeably and include any animal. Mammals, including pets (e.g., cats, dogs) and domesticated mammals (e.g., pigs, horses, cattle), as well as rodents, including mice, rabbits, and rats, guinea pigs, and other rodents, are preferred. Non-human primates are more preferred, and humans are highly preferred.

[0081] As used herein, “MOSPD2” refers to any polypeptide classified as motile sperm domain-containing protein 2. Examples of MOSPD2 include, but are not limited to, the polypeptides of SEQ ID NOs. 26–29 or any variant thereof (e.g., having a sequence at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to any one of SEQ ID NOs. 26–29). Other examples of MOSPD2 include, but are not limited to, polypeptides encoded by any one of SEQ ID NOs. 30–33, or any variant thereof (e.g., polynucleotides at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to any one of SEQ ID NOs. 30–33). The polynucleotide sequences encoding MOSPD2 can be codon-optimized for expression in specific organisms by methods known in the art. Other examples of MOSPD2 can be identified by searching public databases well known to those skilled in the art (e.g., BLAST).

[0082] The "constant region" of an antibody refers to the constant region of either the antibody light chain or the antibody heavy chain, either alone or in combination.

[0083] The term “Fc region” is used to define the C-terminal region of an immunoglobulin heavy chain. The “Fc region” can be a native sequence Fc region or a mutant 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 the amino acid residue at position Cys226 or Pro230 to its carboxyl terminus. The numbering of residues in the Fc region is based on EU index numbering, such as that used by Kabat et al. (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed., Public Health Service, National Institutes of Health, Bethesda, Md., 1991). The Fc region of an immunoglobulin generally contains two constant domains, CH2 and CH3.

[0084] "Specifically binding" generally means that an antibody, or a fragment, variant, or derivative of an antibody, binds to an epitope via its antigen-binding domain, and that the binding involves some complementarity between the antigen-binding domain and the epitope. According to this definition, an antibody, or a fragment, variant, or derivative of an antibody, is said to "specifically bind" to an epitope when it binds to that epitope via its antigen-binding domain more easily than it would bind to a random, unrelated epitope.

[0085] The term "inflammatory cells" includes, but is not limited to, leukocytes, granulocytes, neutrophils, basophils, eosinophils, monocytes, macrophages, lymphocytes, mast cells, and dendritic cells.

[0086] The term “identity percentage” known in the art is the relationship between two or more polypeptide sequences or two or more polynucleotide sequences, determined by comparing sequences. In the art, “identity” and “sequence identity” also mean the degree of sequence relevance between polypeptide or polynucleotide sequences, which may be determined by matching strings of such sequences. "Identity" and "similarity" can be readily calculated using publicly known methods and publicly available resources, including but not limited to those described in (1) Computational Molecular Biology (Lesk, AM, Ed.) Oxford University: NY (1988); (2) Biocomputing: Informatics and Genome Projects (Smith, DW, Ed.) Academic: NY (1993); (3) Computer Analysis of Sequence Data, Part I (Griffin, AM, and Griffin, HG, Eds.) Humania: NJ (1994); (4) Sequence Analysis in Molecular Biology (von Heinje, G., Ed.) Academic (1987); and (5) Sequence Analysis Primer (Gribskov, M. and Devereux, J., Eds.) Stockton: NY (1991).

[0087] As used in this disclosure and the attached claims, the singular forms "a," "an," and "the" refer to multiple subjects unless the context clearly indicates otherwise.

[0088] Whenever an aspect of this disclosure is described herein in the phrase "including," it is understood that other similar aspects described with respect to "consisting of" and / or "essentially consisting of" are also presented.

[0089] Where used herein, the term “or” is understood to be inclusive unless otherwise specifically stated or evident from the context. Where “and / or” is used herein in phrases such as “A and / or B,” it is intended to include both “A and B,” “A or B,” and “A,” and “B.” Similarly, where “and / or” is used in phrases such as “A, B, and / or C,” it is intended to include each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0090] Where used herein, the terms “about” and “approximately” indicate that, when used to modify a number or range of numbers, a deviation of ±10% of the value or range remains within the intended meaning of the listed value or range. As will be understood by those skilled in the art, any reference to a value or range “about” herein includes (and describes) the value or range itself. For example, a statement indicating “about X” includes a statement indicating “X.”

[0091] Any composition or method provided herein may be combined with one or more other compositions and methods provided herein.

[0092] Throughout this application, various aspects of the invention may be presented in range form. It should be understood that range form descriptions are merely for convenience and brevity and should not be interpreted as inflexible limitations on the scope of the invention. Therefore, range descriptions should be considered to specifically disclose all possible subranges and the individual numbers within those ranges. For example, a range description such as 1-6 should be considered to specifically disclose subranges such as 1-3, 1-4, 1-5, 2-4, 2-6, 3-6, and the individual numbers within those ranges, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of the width of the range. Anti-MOSPD2 antibody and its antigen-binding fragment

[0093] In some embodiments, the disclosure provides an antibody or antigen-binding fragment thereof that specifically binds to MOSPD2. In some embodiments, the disclosure provides an antibody or antigen-binding fragment thereof that specifically binds to MOSPD2, comprising, or essentially comprising: (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having approximately 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing an amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) A light chain CDR1 containing an amino acid sequence of any one of SEQ ID NOs. 10-18, or a sequence having approximately 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having approximately 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0094] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0095] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising: a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0096] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0097] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0098] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0099] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0100] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0101] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0102] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0103] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0104] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0105] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 6; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0106] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 6; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 14; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 23; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0107] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0108] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 8; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0109] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0110] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 16; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0111] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0112] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 18; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0113] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0114] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0115] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0116] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0117] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0118] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0119] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0120] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0121] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0122] In some embodiments, the present disclosure provides an antibody or an antigen-binding fragment thereof comprising a heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; a heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; a light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; a light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and a light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25.

[0123] In other embodiments, the antibody or its antigen-binding fragment includes a constant region. In some embodiments, the constant region of the light chain includes the amino acid sequence of the human kappa light chain constant region or the human lambda light chain constant region. In some embodiments, the constant region of the heavy chain includes the amino acid sequence of the human gamma heavy chain constant region. Non-limiting examples of human constant region sequences are described; see, for example, U.S. Patent No. 5,693,780 and Kabat, EA et al., (1991).

[0124] In some embodiments, the disclosure provides an antibody or antigen-binding fragment thereof that specifically binds to MOSPD2, comprising, or essentially comprising, the following: (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1 (e.g., about 1 to about 20 conservative substitutions, or any value within that range); (ii) Heavy chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 2-8, or a sequence having one or more conserved substitutions in SEQ ID NOs. 2-8 (e.g., about 1 to about 20 conserved substitutions, or any value within that range); (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9 (e.g., about 1 to about 20 conservative substitutions, or any value within that range); (iv) Light chain CDR1 containing any one amino acid sequence of sequence numbers 10-18, or a sequence having one or more conservative substitutions in any one of sequence numbers 10-18 (e.g., about 1 to about 20 conservative substitutions, or any value within that range); (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conserved substitutions in any one of SEQ ID NOs. 19-24 (e.g., about 1 to about 20 conserved substitutions, or any value within that range); and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25 (e.g., about 1 to about 20 conservative substitutions, or any value within that range).

[0125] In some embodiments, a conservative substitution is the substitution of an amino acid with a different amino acid having similar charge, hydrophobicity, and / or size. In some embodiments, a conservative substitution is the substitution of one or more amino acids from Table 1 with another amino acid of the same class. JPEG0007879612000001.jpg2862

[0126] Methods for making substitutions in amino acid sequences are known in the art, for example, as described in Yampolsky et al., "The Exchangeability of Amino Acids in Proteins," Genetics. 170(4):1459-1472;2005.

[0127] The antibody or its antigen-binding fragment is preferably monoclonal, and more preferably a full-length antibody comprising two heavy chains and two light chains. In some embodiments, the antibody or its antigen-binding fragment comprises a derivative, fragment, or part of an antibody that retains the antigen-binding specificity of a full-length recombinant antibody, and preferably retains most or all of its affinity. For example, a derivative may include at least one variable region (either a heavy chain variable region or a light chain variable region). Other suitable antibody derivatives and fragments include, but are not limited to, antibodies with polyepitope specificity, bispecific antibodies, multispecific antibodies, diabodies, single-chain molecules, and FAb, F(Ab')2, Fd, Fabc, and Fv molecules, single-chain (Sc) antibodies, single-chain Fv antibodies (scFv), individual antibody light chains, individual antibody heavy chains, fusions between antibody chains and other molecules, heavy chain monomers or dimers, light chain monomers or dimers, dimers consisting of one heavy chain and one light chain, and other polymers. Single-chain Fv antibodies may be polyvalent. Antibody derivatives, fragments, and moieties can be produced using all antibody isotypes. These antibody derivatives, fragments, and / or moieties can be recombinantly produced and expressed by any cell type, prokaryotes, or eukaryotes.

[0128] In full-length antibodies, each heavy chain consists of a heavy chain variable region and a heavy chain constant region. The heavy chain constant region consists of three domains: CH1, CH2, and CH3. Each light chain consists of a light chain variable region (hereinafter abbreviated as LCVR or VL) and a light chain constant region. The light chain constant region consists of one domain, CL. The VH and VL regions can be further subdivided into hypervariable regions called complementarity-determining regions (CDRs), which are interspersed with more conserved regions called framework regions (FRs). Each VH and VL consists of three CDRs and four FRs arranged from the amino terminus to the carboxyl terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. Typically, the antigen-binding properties of an antibody are less likely to be interfered with by changes in the FR sequence than by changes in the CDR sequence. Immunoglobulin molecules can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), a class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or a subclass.

[0129] In some embodiments, an antibody or its antigen-binding fragment is entirely human. A fully human antibody is one in which the entire molecule is human or of other human origin, or contains the same amino acid sequence as the human form of the antibody. Fully human antibodies include, for example, those obtained from a human V gene library in which the human gene encoding the variable region of the antibody is recombinantly expressed. Fully human antibodies may be expressed in cells of other organisms (e.g., mice and xenomouse technology) or cells of other organisms transformed with the gene encoding the human antibody. Nevertheless, fully human antibodies may contain amino acid residues not encoded by the human sequence, such as mutations introduced by random or site-directed mutations.

[0130] In some embodiments, the antibody or its antigen-binding fragment comprises a protein framework derived from non-immunoglobulins. For example, Ku & Schutz, Proc. Natl. Acad. Sci. USA, 92:6552-6 (1995) describes a quadrihelix bundle protein cytochrome b562 having two randomized loops to produce a CDR selected for antigen binding.

[0131] In some embodiments, the recombinant or antigen-binding fragment includes post-translational modifications or moieties that may affect the activity or stability of the antibody. These modifications or moieties include, but are not limited to, methylation, acetylation, glycosylation, sulfation, phosphorylation, carboxylation, and amidation moieties, as well as other moieties well known in the art. The moieties include any chemical group or combination of groups commonly found in natural immunoglobulin molecules or added to antibodies by recombinant expression systems, including prokaryotic and eukaryotic expression systems.

[0132] Examples of side-chain modifications intended by this disclosure include: reaction with aldehydes followed by reduction alkylation with NaBH4; amidation with methyl acetimidate; acylation with acetic anhydride; carbamoylation of the amino group with cyanate; trinitrobenzylation of the amino group with 2,4,6-trinitrobenzenesulfonic acid (TNBS); acylation of the amino group with succinic anhydride and tetrahydrophthalic anhydride; and modification of the amino group by pyridoxylation of lysine with pyridoxal-5-phosphate followed by reduction with NaBH4.

[0133] In some embodiments, the antibody or its antigen-binding fragment includes one or more modifications that modulate the serum half-life and in vivo distribution, including, but not limited to, modifications that modulate the antibody's interaction with neonatal Fc receptor (FcRn), a receptor that plays a crucial role in protecting IgG from catabolism and maintaining high serum antibody concentrations.

[0134] Antibodies or their antigen-binding fragments can be labeled, conjugated, or conjugated to any chemical or biomolecular portion. Labeled antibodies can find use in therapeutic, diagnostic, or basic research applications. Such labels / conjugates can be detectable and may include fluorescent dyes, electrochemiluminescent probes, quantum dots, radiolabels, enzymes, fluorescent proteins, luminescent proteins, and biotin. Labels / conjugates may also be chemotherapeutic agents, toxins, isotopes, and other drugs used to treat conditions such as cancer cell death. The chemotherapeutic agent may be any suitable for the purpose in which the antibody is being used.

[0135] In some embodiments, an antibody or its antigen-binding fragment may be derivatized with a known protective / inhibitory group to prevent proteolytic cleavage or to enhance activity or stability.

[0136] In some embodiments, the antibody or its antigen-binding fragment is a polyclonal antibody, a monoclonal antibody, a mouse antibody, a human antibody, a humanized antibody, or a chimeric antibody.

[0137] In some embodiments, the antibody or its antigen-binding fragment is a Fab, Fab', F(ab')2, Fv, scFv, sdFv fragment, VH domain, VL domain, or a combination thereof.

[0138] In some embodiments, the antibody or its antigen-binding fragment is IgG, IgM, IgE, IgA, IgD, its variants, or a combination thereof. In some embodiments, the antibody or its antigen-binding fragment is IgG1, IgG2, IgG3, IgG4, its variants, or a combination thereof.

[0139] In some embodiments, approximately 1 × 10 5 (1 / Ms) ~ approx. 7×10 6 The value of Ka (1 / Ms); approximately 1 × 10⁻⁶ -4 (1 / s) ~ a Kd value of approximately 0.4(1 / s); and / or approximately 2 × 10 -10 (M)~Approx. 6×10-8 (M) is bound to MOSPD2 with the calculated KD.

[0140] In some embodiments, the Disclosure provides antibodies or antigen-binding fragments that specifically bind to MOSPD2, where MOSPD2 is human MOSPD2.

[0141] In some embodiments, the disclosure provides antibodies or antigen-binding fragments that specifically bind to MOSPD2 having an amino acid sequence of any one of SEQ ID NOs. 26-29, or an amino acid sequence having approximately 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity with any one of SEQ ID NOs. 26-29.

[0142] In some embodiments, the Disclosure provides antibodies or antigen-binding fragments that specifically bind to MOSPD2 having an amino acid sequence encoded by any one of the nucleic acid sequences of SEQ ID NOs. 30-33, or an amino acid sequence having approximately 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity with any one of SEQ ID NOs. 30-33.

[0143] In some embodiments, this disclosure provides antibodies or antigen-binding fragments that compete for binding to MOSPD2 with the antibodies or antigen-binding fragments described herein. Binding competition can be determined using assays known to those skilled in the art, including but not limited to ELISA competition assays, surface plasmon resonance, and scatchard analysis.

[0144] In some embodiments, the Disclosure provides nucleic acids encoding antibodies or antigen-binding fragments thereof that specifically bind to MOSPD2. In some embodiments, the Disclosure provides vectors comprising nucleic acids encoding antibodies or antigen-binding fragments thereof that specifically bind to MOSPD2. In some embodiments, the Disclosure provides vectors comprising nucleic acids encoding antibodies or antigen-binding fragments thereof that specifically bind to MOSPD2, or cells comprising nucleic acids encoding antibodies or antigen-binding fragments thereof that specifically bind to MOSPD2.

[0145] In some embodiments, the Disclosure provides a method for producing an antibody or antigen-binding fragment that specifically binds to MOSPD2, comprising culturing cells comprising a vector comprising a nucleic acid encoding the antibody or antigen-binding fragment described herein that specifically binds to MOSPD2 under appropriate conditions, and isolating the antibody or antigen-binding fragment. Compositions and kits

[0146] In some embodiments, the Disclosure provides compositions comprising the antibody or antigen-binding fragment described herein. In some embodiments, the Disclosure provides compositions comprising the antibody or antigen-binding fragment comprising: (i) the amino acid sequence of SEQ ID NO: 1, or a heavy chain CDR1 comprising a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) Light chain CDR1 containing an amino acid sequence of any one of sequence numbers 10-18, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of sequence numbers 10-18; (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0147] In some embodiments, the Disclosure provides compositions comprising an antibody or antigen-binding fragment thereof that specifically binds to MOSPD2, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence in SEQ ID NOs: 2-8 having one or more conservative substitutions; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; (iv) A light chain CDR1 containing any one amino acid sequence from sequence numbers 10 to 18, or a sequence in any one of sequence numbers 10 to 18 having one or more conservative substitutions; (v) Light chain CDR2 comprising any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conservative substitutions in any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0148] In some embodiments, the composition comprises an antibody or antigen-binding fragment as described herein, and a carrier. In some embodiments, the carrier is a diluent, adjuvant, excipient, or vehicle administered together with the compound. Examples of carriers include, but are not limited to, liquids such as water and oil. Water, aqueous saline solutions, and aqueous solutions of dextrose and glycerol can also be used as carriers, particularly for injectable solutions.

[0149] In some embodiments, the composition is formulated for administration by injection or infusion. Routes of administration by injection or infusion include intravenous, intraperitoneal, intramuscular, intrathecal, and subcutaneous.

[0150] In some embodiments, the disclosure provides a nucleic acid encoding an antibody or antigen-binding fragment thereof as described herein, a vector comprising such nucleic acid, or a composition comprising a cell comprising such nucleic acid or vector. In some embodiments, the composition further comprises a carrier.

[0151] In some embodiments, the Disclosure provides (i) an antibody or antigen-binding fragment as described herein, a nucleic acid encoding the antibody or antigen-binding fragment as described herein, a vector comprising such nucleic acid, or a cell comprising such nucleic acid or vector, and (ii) a kit comprising instructions for use.

[0152] In some embodiments, the present disclosure provides compositions comprising the antibody or antigen-binding fragment described herein and one or more additional activators. Usage

[0153] In some embodiments, the Disclosure provides a method for treating or preventing an inflammatory disease or disorder, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, the Disclosure provides a method for treating or preventing an inflammatory disease or disorder, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment comprising the following to a subject in need thereof: (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) Light chain CDR1 containing an amino acid sequence of any one of sequence numbers 10-18, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of sequence numbers 10-18; (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0154] In some embodiments, the present disclosure provides a method for treating or preventing an inflammatory disease or disorder, comprising administering to a subject in need an antibody or antigen-binding fragment that specifically binds to MOSPD2 in a therapeutically effective amount, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence in SEQ ID NOs: 2-8 having one or more conservative substitutions; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; (iv) A light chain CDR1 containing any one amino acid sequence from sequence numbers 10 to 18, or a sequence in any one of sequence numbers 10 to 18 having one or more conservative substitutions; (v) Light chain CDR2 comprising any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conservative substitutions in any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0155] In some aspects, inflammatory diseases or disorders include idiopathic inflammatory diseases or disorders, chronic inflammatory diseases or disorders, acute inflammatory diseases or disorders, autoimmune diseases or disorders, infectious diseases or disorders, inflammatory malignant diseases or disorders, inflammatory transplant-related diseases or disorders, inflammatory degenerative diseases or disorders, hypersensitivity-related diseases or disorders, inflammatory cardiovascular diseases or disorders, inflammatory cerebrovascular diseases or disorders, peripheral vascular diseases or disorders, inflammatory gonadal diseases or disorders, inflammatory gastrointestinal diseases or disorders, inflammatory skin diseases or disorders, inflammatory liver diseases or disorders, inflammatory neurological diseases or disorders, inflammatory musculoskeletal diseases or disorders, inflammatory kidney diseases or disorders, inflammatory reproductive diseases or disorders, inflammatory systemic diseases or disorders, inflammatory connective tissue diseases or disorders, necrosis, inflammatory implant-related diseases or disorders, inflammatory aging processes, immunodeficiency diseases or disorders, or inflammatory lung diseases or disorders.

[0156] In some embodiments, hypersensitivity is type I hypersensitivity, type II hypersensitivity, type III hypersensitivity, type IV hypersensitivity, immediate-type hypersensitivity, antibody-mediated hypersensitivity, immune complex-mediated hypersensitivity, T lymphocyte-mediated hypersensitivity, delayed-type hypersensitivity, helper T lymphocyte-mediated hypersensitivity, cytotoxic T lymphocyte-mediated hypersensitivity, TH1 lymphocyte-mediated hypersensitivity, or TH2 lymphocyte-mediated hypersensitivity.

[0157] In some aspects, inflammatory cardiovascular disease or disorder is obstructive disease or disorder, atherosclerosis, valvular heart disease, stenosis, restenosis, in-stent stenosis, myocardial infarction, coronary artery disease, acute coronary syndrome, congestive heart failure, angina pectoris, myocardial ischemia, thrombosis, Wegener's granulomatosis, Takayasu's arteritis, Kawasaki syndrome, anti-factor VIII autoimmune disease or disorder, necrotizing small vessel vasculitis, microscopic polyangiitis, Churg-Strauss syndrome, minority immune focal segmental necrotizing glomerulonephritis, crescent glomerulonephritis, antiphospholipid syndrome, antibody-induced heart failure, thrombocytopenic purpura, autoimmune hemolytic anemia, cardiac autoimmunity, Chagas disease or disorder, or anti-helper T lymphocyte autoimmunity.

[0158] In some embodiments, inflammatory cerebrovascular disease or disorder is a stroke, cerebral vasculitis, cerebral hemorrhage, or vertebral artery insufficiency.

[0159] In some aspects, peripheral vascular disease or disorder may include gangrene, diabetic vascular disease, thrombosis, diabetic retinopathy, or diabetic nephropathy.

[0160] In some aspects, autoimmune diseases or disorders include systemic lupus erythematosus, scleroderma, mixed connective tissue disease, polyarteritis nodosa, polymyositis / dermatomyositis, Sjögren's syndrome, Behçet's disease, autoimmune diabetes, Hashimoto's disease, psoriasis, primary myxedema, pernicious anemia, myasthenia gravis, chronic active hepatitis, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, uveitis, vasculitis, or heparin-induced thrombocytopenia.

[0161] In some aspects, inflammatory gonadal disease or disorder is a pancreatic disease or disorder, type 1 diabetes, thyroid disease or disorder, Graves' disease or disorder, thyroiditis, spontaneous autoimmune thyroiditis, Hashimoto's thyroiditis, idiopathic myxedema, ovarian autoimmunity, autoimmune antispermia, autoimmune prostatitis, or type 1 autoimmune polyglandular syndrome.

[0162] In some embodiments, inflammatory skin diseases or disorders include acne, autoimmune bullous skin diseases or disorders, pemphigus vulgaris, bullous pemphigoid, pemphigus foliaceus, contact dermatitis, or drug eruption.

[0163] In some embodiments, inflammatory liver disease or disorder is autoimmune hepatitis, cirrhosis, or biliary cirrhosis.

[0164] In some embodiments, inflammatory neurological diseases or disorders include Alzheimer's disease, Parkinson's disease, myasthenia gravis, motor neuropathy, Guillain-Barré syndrome, autoimmune neuropathy, Lambert-Eaton myasthenic syndrome, paraneoplastic neurological diseases or disorders, paraneoplastic cerebellar atrophy, non-neoplastic Stiffman syndrome, progressive cerebellar atrophy, Rasmussen encephalitis, amyotrophic lateral sclerosis, Sideham's chorea, Gilles de la Tourette syndrome, autoimmune polyglandular endocrine insufficiency, disimmune neuropathy, acquired neuromuscular dystrophy, polyarthritis, Huntington's disease, AIDS-related dementia, amyotrophic lateral sclerosis, stroke, inflammatory retinal diseases or disorders, inflammatory eye diseases or disorders, optic neuritis, cavernous encephalopathy, migraine, headache, cluster headache, or rigidity syndrome.

[0165] In some embodiments, inflammatory connective tissue diseases or disorders include Duchenne muscular dystrophy (DMD), autoimmune myositis, primary Sjögren's syndrome, smooth muscle autoimmune diseases or disorders, myositis, tendinitis, ligamentitis, chondritis, arthritis, synovitis, carpal tunnel syndrome, ankylosing spondylitis, skeletal inflammation, autoimmune ear diseases or disorders, or autoimmune diseases or disorders of the inner ear.

[0166] In some aspects, inflammatory kidney disease or disorder is autoimmune interstitial nephritis.

[0167] In some embodiments, inflammatory reproductive disorders or conditions include recurrent fetal loss, ovarian cysts, or menstrual disorders or conditions.

[0168] In some embodiments, inflammatory systemic diseases or disorders include systemic lupus erythematosus, systemic sclerosis, septic shock, toxic shock syndrome, or cachexia.

[0169] In some embodiments, infectious diseases or disorders include chronic infectious diseases or disorders, subacute infectious diseases or disorders, acute infectious diseases or disorders, viral diseases or disorders, bacterial diseases or disorders, protozoal diseases or disorders, parasitic diseases or disorders, fungal diseases or disorders, mycoplasma diseases or disorders, gangrene, sepsis, prion diseases or disorders, influenza, tuberculosis, malaria, acquired immunodeficiency syndrome, or severe acute respiratory syndrome.

[0170] In some embodiments, inflammatory graft-related diseases or disorders include graft rejection, chronic graft rejection, subacute graft rejection, acute graft rejection, hyperacute graft rejection, or graft-versus-host diseases or disorders.

[0171] In some embodiments, the implant is an orthotic implant, breast implant, silicone implant, dental implant, penile implant, cardiac implant, artificial joint, fracture repair device, bone replacement implant, drug delivery implant, catheter, pacemaker, artificial heart, artificial heart valve, drug delivery implant, electrode, or ventilator tube.

[0172] In some aspects, inflammatory lung diseases or disorders include asthma, allergic asthma, emphysema, chronic obstructive pulmonary disease or disorder, sarcoidosis, or bronchitis.

[0173] In some embodiments, inflammatory disease or disorder is vasculitis in a subject suffering from a chronic autoimmune disease or chronic inflammatory disease. In some embodiments, the chronic autoimmune disease or inflammatory disease is psoriasis. In some embodiments, vasculitis is associated with cardiovascular disease, peripheral vascular disease, coronary artery disease, cerebrovascular disease, renal artery stenosis, ischemic disease, or aortic aneurysm. In some embodiments, vasculitis is associated with ischemic heart disease, atherosclerosis, acute coronary syndrome, unstable angina, stable angina, or stroke. In other embodiments, vasculitis is inflammation of the carotid arteries. In other embodiments, vasculitis is inflammation of the aorta.

[0174] In some embodiments, the inflammatory disease or disorder is inflammation associated with the implant. In some embodiments, the inflammation associated with the implant is local inflammation or a systemic inflammatory response. In some embodiments, the implant is a silicone, saline, metal, plastic, or polymer implant. In some embodiments, the implant is a cosmetic implant, artificial implant, subcutaneous implant, percutaneous implant, bone replacement implant, or fracture repair device. In some embodiments, the implant is a drug delivery implant or drug release implant. In other embodiments, the implant is a joint prosthesis, artificial heart, artificial heart valve, testicular prosthesis, breast implant, dental implant, ocular implant, cochlear implant, penile implant, cardiac implant, catheter, implantable urinary incontinence device, pacemaker, electrode, hernia support device, or ventilator tube.

[0175] In some embodiments, the Disclosure provides a method for inhibiting or preventing the migration of inflammatory cells (e.g., monocytes or neutrophils), comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject requiring such inhibition. (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) Light chain CDR1 containing an amino acid sequence of any one of sequence numbers 10-18, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of sequence numbers 10-18; (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0176] In some embodiments, the present disclosure provides a method for inhibiting or preventing the migration of inflammatory cells (e.g., monocytes or neutrophils) comprising administering to a subject in need of such inhibition or prevention an antibody or antigen-binding fragment that specifically binds to MOSPD2 in a therapeutically effective amount, i.e. (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence in SEQ ID NOs: 2-8 having one or more conservative substitutions; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; (iv) A light chain CDR1 containing any one amino acid sequence from sequence numbers 10 to 18, or a sequence in any one of sequence numbers 10 to 18 having one or more conservative substitutions; (v) Light chain CDR2 comprising any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conservative substitutions in any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0177] In some embodiments, the Disclosure provides a method for treating or preventing non-alcoholic fatty liver disease (NAFLD), steatohepatitis, or non-alcoholic steatohepatitis (NASH), comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need. In some embodiments, the Disclosure provides a method for treating or preventing non-alcoholic fatty liver disease (NAFLD), steatohepatitis, or non-alcoholic steatohepatitis (NASH), comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment comprising the following to a subject in need: (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) Light chain CDR1 containing an amino acid sequence of any one of sequence numbers 10-18, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of sequence numbers 10-18; (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0178] In some embodiments, the Disclosure provides a method for treating or preventing non-alcoholic fatty liver disease (NAFLD), steatohepatitis, or non-alcoholic steatohepatitis (NASH), comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment specifically bound to MOSPD2, including the following, to a subject in need: (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence in SEQ ID NOs: 2-8 having one or more conservative substitutions; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; (iv) A light chain CDR1 containing any one amino acid sequence from sequence numbers 10 to 18, or a sequence in any one of sequence numbers 10 to 18 having one or more conservative substitutions; (v) Light chain CDR2 comprising any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conservative substitutions in any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0179] In some embodiments, the Disclosure provides a method for treating or preventing fibrosis, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, the Disclosure provides a method for treating or preventing fibrosis, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment comprising the following to a subject in need thereof, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) Light chain CDR1 containing an amino acid sequence of any one of sequence numbers 10-18, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of sequence numbers 10-18; (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0180] In some embodiments, the present disclosure provides a method for treating or preventing fibrosis, comprising administering to a subject in need thereof an antibody or antigen-binding fragment that specifically binds to MOSPD2 in a therapeutically effective amount, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence in SEQ ID NOs: 2-8 having one or more conservative substitutions; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; (iv) A light chain CDR1 containing any one amino acid sequence from sequence numbers 10 to 18, or a sequence in any one of sequence numbers 10 to 18 having one or more conservative substitutions; (v) Light chain CDR2 comprising any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conservative substitutions in any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0181] In some embodiments, fibrosis is hepatic fibrosis, renal fibrosis, pulmonary fibrosis, cutaneous fibrosis, idiopathic pulmonary fibrosis (IPF), cystic fibrosis, progressive giant fibrosis, cirrhosis, endocardial myocardial fibrosis, myelofibrosis, myelofibrosis, retroperitoneal fibrosis, nephrogenic systemic fibrosis, or articular fibrosis. In some embodiments, renal fibrosis is focal segmental glomerulosclerosis (FSGS) or glomerulosclerosis.

[0182] In some embodiments, the Disclosure provides a method for treating or preventing arthritis (e.g., rheumatoid arthritis or psoriatic arthritis) comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, the Disclosure provides a method for treating or preventing arthritis (e.g., rheumatoid arthritis or psoriatic arthritis) comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment comprising the following to a subject in need thereof, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) Light chain CDR1 containing an amino acid sequence of any one of sequence numbers 10-18, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of sequence numbers 10-18; (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0183] In some embodiments, the present disclosure provides a method for treating or preventing arthritis (e.g., rheumatoid arthritis or psoriatic arthritis) comprising administering to a subject in need of such treatment an effective amount of an antibody or antigen-binding fragment specifically conjugated to MOSPD2, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence in SEQ ID NOs: 2-8 having one or more conservative substitutions; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; (iv) A light chain CDR1 containing any one amino acid sequence from sequence numbers 10 to 18, or a sequence in any one of sequence numbers 10 to 18 having one or more conservative substitutions; (v) Light chain CDR2 comprising any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conservative substitutions in any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0184] In some aspects, arthritis is rheumatoid arthritis, osteoarthritis, juvenile arthritis, or psoriatic arthritis. In some aspects, rheumatoid arthritis is chronic rheumatoid arthritis or juvenile rheumatoid arthritis.

[0185] In some embodiments, the Disclosure provides a method for treating or preventing multiple sclerosis, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, the Disclosure provides a method for treating or preventing multiple sclerosis, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment comprising the following to a subject in need thereof, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) Light chain CDR1 containing an amino acid sequence of any one of sequence numbers 10-18, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of sequence numbers 10-18; (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0186] In some embodiments, the present disclosure provides a method for treating or preventing multiple sclerosis, comprising administering to a subject in need of such treatment an effective amount of an antibody or antigen-binding fragment specifically conjugated to MOSPD2, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence in SEQ ID NOs: 2-8 having one or more conservative substitutions; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; (iv) A light chain CDR1 containing any one amino acid sequence from sequence numbers 10 to 18, or a sequence in any one of sequence numbers 10 to 18 having one or more conservative substitutions; (v) Light chain CDR2 comprising any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conservative substitutions in any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0187] In some embodiments, multiple sclerosis is remittent multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS), or secondary progressive multiple sclerosis (SPMS). In some embodiments, the method further comprises administering a further therapeutic agent. In some embodiments, the method comprises the further therapeutic agent being teriflunomide, natalizumab, dimethyl fumarate, ocrelizumab, IFNβ-1a, cladribine, glatiramer acetate, or a combination thereof.

[0188] In some embodiments, the Disclosure provides a method for treating or preventing colitis or inflammatory bowel disease, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need. In some embodiments, the Disclosure provides a method for treating or preventing colitis or inflammatory bowel disease, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment comprising the following to a subject in need: (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) Light chain CDR1 containing an amino acid sequence of any one of sequence numbers 10-18, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of sequence numbers 10-18; (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0189] In some embodiments, the present disclosure provides a method for treating or preventing colitis or inflammatory bowel disease, comprising administering to a subject in need thereof an antibody or antigen-binding fragment that specifically binds to MOSPD2, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence in SEQ ID NOs: 2-8 having one or more conservative substitutions; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; (iv) A light chain CDR1 containing any one amino acid sequence from sequence numbers 10 to 18, or a sequence in any one of sequence numbers 10 to 18 having one or more conservative substitutions; (v) Light chain CDR2 comprising any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conservative substitutions in any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0190] In some embodiments, the inflammatory bowel disease is ulcerative colitis or Crohn's disease. In some embodiments, the method further includes administering a further therapeutic agent. In some embodiments, the further therapeutic agent is infliximab, vedolizumab, azathioprine, adalimumab, masalazine, or a combination thereof.

[0191] In some embodiments, the Disclosure provides a method for treating or preventing cancer or cancer metastasis, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment described herein to a subject in need thereof. In some embodiments, the Disclosure provides a method for treating or preventing cancer or cancer metastasis, comprising administering a therapeutically effective amount of an antibody or antigen-binding fragment comprising the following to a subject in need thereof, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence of any one of SEQ ID NOs: 2-8, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with one of SEQ ID NOs: 2-8; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 9; (iv) Light chain CDR1 containing an amino acid sequence of any one of sequence numbers 10-18, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of sequence numbers 10-18; (v) Light chain CDR2 containing any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having approximately 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25, or a sequence having 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more identity with SEQ ID NO: 25.

[0192] In some embodiments, the present disclosure provides a method for treating or preventing cancer or cancer metastasis, comprising administering to a subject in need of such treatment an effective amount of an antibody or antigen-binding fragment specifically bound to MOSPD2, namely, (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1 or a sequence having one or more conservative substitutions in SEQ ID NO: 1; (ii) Heavy chain CDR2 containing one amino acid sequence from SEQ ID NOs: 2-8, or a sequence in SEQ ID NOs: 2-8 having one or more conservative substitutions; (iii) Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9 or a sequence having one or more conservative substitutions in SEQ ID NO: 9; (iv) A light chain CDR1 containing any one amino acid sequence from sequence numbers 10 to 18, or a sequence in any one of sequence numbers 10 to 18 having one or more conservative substitutions; (v) Light chain CDR2 comprising any one amino acid sequence of SEQ ID NOs. 19-24, or a sequence having one or more conservative substitutions in any one of SEQ ID NOs. 19-24; and (vi) A light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 25 or a sequence having one or more conservative substitutions in SEQ ID NO: 25.

[0193] In some aspects, cancer is bladder cancer, breast cancer, colon cancer, ovarian cancer, rectal cancer, kidney cancer, liver cancer, lung cancer, esophageal cancer, gallbladder cancer, ovarian cancer, pancreatic cancer, stomach cancer, cervical cancer, thyroid cancer, prostate cancer, skin cancer, hematopoietic cancer, mesenchymal cancer, central or peripheral nervous system cancer, endometrial cancer, head and neck cancer, glioblastoma, malignant ascites, neuroendocrine cancer, gastrointestinal cancer, or recurrent or primary cancer.

[0194] In some aspects, lung cancer is either small cell lung cancer or non-small cell lung cancer.

[0195] In some aspects, skin cancer is squamous cell carcinoma, basal cell carcinoma, melanoma, dermatofibrosarcoma protuberance, Merkel cell carcinoma, Kaposi's sarcoma, keratoacanthoma, spindle cell tumor, sebaceous carcinoma, microcystic adnexal carcinoma, Paget's disease of the breast, atypical fibroxanthoma, leiomyosarcoma, or angiosarcoma.

[0196] In some aspects, hematopoietic carcinoma is a lymphatic hematopoietic carcinoma. In some aspects, lymphatic hematopoietic carcinoma is leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, hairy cell lymphoma, or Burkitt lymphoma.

[0197] In some embodiments, hematopoietic carcinomas are myeloid hematopoietic carcinomas. In some embodiments, myeloid hematopoietic carcinomas include acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndromes, and promyelocytic leukemias.

[0198] In some aspects, cancers of mesenchymal origin are fibrosarcoma, rhabdomyosarcoma, soft tissue sarcoma, or osteosarcoma.

[0199] In some aspects, cancers of the central or peripheral nervous system are astrocytoma, neuroblastoma, glioma, schwann cell tumor, or glioblastoma.

[0200] In some embodiments, cancer is anal cancer, bone cancer, gastrointestinal stoma cancer, gestational trophoblastic disease, Hodgkin lymphoma, Kaposi's sarcoma, keratoacanthoma, malignant mesothelioma, multicentric Castleman disease, multiple myeloma and other plasma cell neoplasms, myeloproliferative neoplasms, neuroblastoma, non-Hodgkin lymphoma, osteosarcoma, ovarian cancer, fallopian tube cancer or primary peritoneal cancer, penile cancer, retinoblastoma, rhabdomyosarcoma, seminoma, soft tissue sarcoma, stomach (gastric) cancer, testicular cancer, teratoma, follicular thyroid cancer, vaginal cancer, vulvar cancer, Wilms' tumor and other pediatric kidney cancers, or xeroderma pigmentosum.

[0201] In some embodiments, the method further comprises administering a further therapeutic agent to the target. In some embodiments, the further therapeutic agent is an anticancer agent. In some embodiments, the anticancer agent is abiraterone acetate, abitrexate (methotrexate), Abraxane (paclitaxel albumin-stabilized nanoparticle formulation), ABVD, ABVE, ABVE-PC, AC, AC-T, Adcetris (brentuximab vedotin), ADE, Ado-trastuzumab emtansine, Adriamycin (doxorubicin hydrochloride), Adolsil (fluorouracil), afatinib dimaleate, Afinitor (everolimus), Aquinzeo (netpitant and paro Nosetron hydrochloride), Aldara (imiquimod), Aldesleukin, Alemtuzumab, Alimta (pemetrexed disodium), Aloxi (palonosetron hydrochloride), Ambochorin (chlorambucil), Ambochorin (chlorambucil), Aminolevulinic acid, Anastrozole, Aprepitant, Aredia (pamidronate disodium), Arimidex (anastrozole), Aromasin (exemestane), Alanone (nelarabine), Arsenic trioxide, Alzera (ofatumumab), Erwinia Chrysanthemi-derived asparaginase, Avastin (bevacizumab), axitinib, azacitidine, BEACOPP, Besenam (carmustine), Belenodac (bellinostat), bellinostat, bendamustine hydrochloride, BEP, bevacizumab, bexarotene, Vexar (tositumomab and iodine (I131) tositumomab), bicalutamide, BiCNU (carmustine), bleomycin, blinatumomab, Brincyt (blinatumomab), bortezomib, Boslif (bosutinib), Bos Tinib, brentuximab vedotin, busulfan, busulfex (busulfan), cabazitaxel, cabozantinib-S-malate, CAF, Campas (alemtuzumab), camptosar (irinotecan hydrochloride), capecitabine, CAPOX, carboplatin, carboplatin-taxol, carfilzomib, carmbris (carmustine), carmustine, carmustine implant, Casodex (bicalutamide), CeeNU (lomustine), ceritinib, selvidine (daunorubicin hydrochloride),Cervarix (recombinant HPV bivalent vaccine), cetuximab, chlorambucil, chlorambucil-prednisone, CHOP, cisplatin, Clafen (cyclophosphamide), clofarabine, CMF, Cometrix (cabozantinib-S-malate), COPP, COPP-ABV, Cosmegen (dactinomycin), crizotinib, CVP, cyclophosphamide, Cyfos (ifosfamide), Cyramza (ramucirumab), cytarabine, cytarabine, liposome, Cytosar-U (cytarabine), Cy Toxan (cyclophosphamide), dabrafenib, dacarbazine, Dacogen (decitabine), dactinomycin, dasatinib, daunorubicin hydrochloride, decitabine, degarelix, denileukin diffitox, denosumab, Deposite (liposomal cytarabine), Depoform (liposomal cytarabine), dexrazoxane hydrochloride, dinutuximab, docetaxel, Doxil (doxorubicin hydrochloride liposome), doxorubicin hydrochloride, doxorubicin hydrochloride liposome, Dox-SL (doxorubicin hydrochloride Liposomes), DTIC-Dome (dacarbazine), Efudex (fluorouracil), Elitek (rasburicase), Ellence (epirubicin hydrochloride), Eloxatin (oxaliplatin), Eltrombopagolamine, Emend (aprepitant), Enzalutamide, Epirubicin hydrochloride, EPOCH, Erbitux (cetuximab), Eribulin mesylate, Elvege (bismodegib), Erlotinib hydrochloride, Elwinase (asparaginase erwinia chrysanthemis), Etopophos (etopophos phosphate) D), etoposide, etoposide phosphate, Evaset (doxorubicin hydrochloride liposome), everolimus, Evista (raloxifene hydrochloride), exemestane, Fareston (toremifene), Farydak (panobinostat), Faslodex (fulvestrant), FEC, Femara (letrozole), Filgrastim, Fludara (fludarabine phosphate), fludarabine phosphate, fluoroplex (fluorouracil), fluorouracil, Forex (methotrexate), Forex PFS (methotrexate), FOLFIRI, FOLFIRI-bevacizumab, FOLFIRI-cetuximab,FOLFIRINOX, FOLFROX, Forotin (pralatrexate), FU-LV, fulvestrant, Gardasil (recombinant HPV quadrivalent vaccine), Gardasil 9 (recombinant HPV non-valent vaccine), Gazyva (obinutuzumab), gefitinib, gemcitabine hydrochloride, gemcitabine-cisplatin, gemcitabine-oxaliplatin, gemtuzumab ozogamicin, gemzar (gemcitabine hydrochloride), zirotrif (afatinib dimarate), gleevec (imatinib mesylate), gliadel (carmustine implant), gliadel wafer (carmustine implant), glucarpidase, goserelin acetate, halaben (eribulin mesylate), Herceptin (Trastuzumab), HPV bivalent vaccine, recombinant, HPV nonavalent vaccine, recombinant, HPV tetravalent vaccine, recombinant, Hycamtin (topotecan hydrochloride), Hyper-CVAD, Ibrance (palbociclib), ibritumomab tiuxetan, ibrutinib, ICE, Iclusig (ponatinib hydrochloride), Idamycin (idarubicin hydrochloride), idarubicin hydrochloride, idelalisib, Ifex (ifosfamide), ifosfamide, ifosfamidedam (ifosfamide), imatinib mesylate, imbrubi Ca (ibrutinib), imiquimod, Inlyta (axitinib), Intron A (recombinant interferon alpha-2b), iodine-131 tositumomab and tositumomab, ipilimumab, Iressa (gefitinib), irinotecan hydrochloride, Istodax (romidepsin), ixabepirone, Ixempra (ixabepirone), Jakafi (ruxolitinib phosphate), Jevtana (cabazitaxel), Kadcyla (adtrastuzumab emtansine), Keoxifen (raloxifene hydrochloride), Kepivans (Palifermin), Keytruda (pembrolizumab), Cyprolis (carfilzomib), lanreotide acetate, lapatinib distosylate, lenalidomide, lenvatinib mesylate, Lenvima (lenvatinib mesylate), letrozole, leucovorin calcium, Leukeran (chlorambucil), leuprolide acetate, Leblanc (aminolevulinic acid), lymphoridine (chlorambucil), Lipodox (doxorubicin hydrochloride liposome), liposomal cytarabine, lomustine, Lupron (leuprolide acetate),Lupron Depot (leuprolide acetate), Lupron Depot-Ped (leuprolide acetate), Lupron Depot-3Month (leuprolide acetate), Lupron Depot-4Month (leuprolide acetate), Lynparza (olaparib), Marqibo (vincristine liposome sulfate), Matulane (procarbazine hydrochloride), mechloretamine hydrochloride, Megace (megestrol acetate), megestrol acetate, Mekinist (trametinib), mercaptopurine, Mesna, Mesnex (mesna), Mesazolastone (temozolomide), methotrexate, methotrexate LPF (methotrexate), Mexate (methotrexate) Trexate, Mexate-AQ (methotrexate), Mitomycin C, Mitoxantrone hydrochloride, Mitozytrex (mitomycin C), MOPP, Mozovir (plelixafor), Mastergen (mechloretamine hydrochloride), Mutamycin (mitomycin C), Myrelan (busulfan), Myrosal (azacitidine), Mylotarg (gemtuzumab ozogamicin), Nanoparticle paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation), Navelbine (vinorelbine tartrate), Nelarbine, Neosar (cyclophosphamide), Netupitant, and Palonosetron Hydrochloride, Neupogen (filgrastim), Nexavar (sorafenib tosylate), Nilotinib, Nivolumab, Nolvadex (tamoxifen citrate), Nplate (Romiplostim), Obinutuzumab, OEPA, Ofatumumab, OFF, Olaparib, Omasetaxin mepesuccinate, Oncaspar (pegaspar gauze), Ontac (denileukin diffitox), Opdivo (nivolumab), OPPA, O Xaliplatin, paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation, PAD, palbociclib, parifermin, palonosetron hydrochloride, pamidronate disodium, panitumumab, panobinostat, paraplatin (carboplatin), paraplatin (carboplatin), pazopanib hydrochloride, pegaspargase, pegylated interferon alfa-2b, PEG-intron (pegylated interferon alfa-2b), pembrolizumab, pemetrexed disodium,Perjeta (pertuzumab), pertuzumab, Platinol (cisplatin), Platinol-AQ (cisplatin), prelixafor, pomalidomide, Pomalist (pomalidomide), ponatinib hydrochloride, pralatrexate, prednisone, procarbazine hydrochloride, proleukin (aldesleukin), Prolia (denosumab), Promacta (eltrombopagolamine), Provenge (ciproisel-T), Prinetol (mercaptopurine), Prixan (mercaptopurine), radium-223 dichloride, raloxifene hydrochloride, ramucirumab, Rasburicase, R-CHOP, R-CVP, Recombinant Human Papillomavirus (HPV) Bivalent Vaccine, Recombinant Human Papillomavirus (HPV) Monovalent Vaccine, Recombinant Human Papillomavirus (HPV) Quadravalent Vaccine, Recombinant Interferon Alpha-2b, Regorafenib, R-EPOCH, Revlimid (Lenalidomide), Rheumatoid Arthritis (Methotrexate), Rituxan (Rituximab), Rituximab, Romidepsin, Romiplostim, Rubidomycin (Daunorubicin Hydrochloride), Ruxolitinib Phosphate, Intrapleural Sclerosol Aerosol (Tal) ), siltuximab, ciproisel-T, somatuline depot (lanreotide acetate), sorafenib tosylate, sprycel (dasatinib), stanford V, sterile talc powder (talc), steritalc (talc), stivarga (regorafenib), sunitinib malate, suten (sunitinib malate), cilatron (pegylated interferon alfa-2b), silvant (siltuximab), cinobir (thalidomide), cinribo (omepe succinate omacetaxine), TAC, tafinlar (dabrafenib), talc, tamoxifenib citrate Yen, Tarabine PFS (cytarabine), Tarceva (erlotinib hydrochloride), Targretin (bexarotene), Tasigna (nilotinib), Taxol (paclitaxel), Taxotere (docetaxel), Temodal (temozolomide), temozolomide, temsirolimus, thalidomide, salomide (thalidomide), thiotepa, toposal (etoposide), topotecan hydrochloride, toremifene, Tricel (temsirolimus), tositumomab and I131 iodine tositumomab, Totect (dexrazoxane hydrochloride), TPF, trametinib, trastuzumab,Treanda (bendamustine hydrochloride), Trisenox (arsenic trioxide), Tykerb (lapatinib ditosylate), Unituxin (dinutuximab), Vandetanib, VAMP, Vectibix (panitumumab), VeIP, Velban (vinblastine sulfate), Velcade (bortezomib), Velsar (vinblastine sulfate), Vemurafenib, VePesid (etoposide), Viadur (leuprolide acetate), Vidaza (azacitidine), vinblastine sulfate, Vincasar PFS (vincristine sulfate), vincristine sulfate, vincristine sulfate liposomes, vinorelbine tartrate, VIP, bismodegib, Boraxase (glucarpidase), vorinostat, Botrient (pazopanib hydrochloride), Welcovorin (leucovorin calcium), Xalkori (crizotinib), Xeloda (capesita) These include Bin), Jellyli, Xerox, Zegeba (denosumab), Zofigo (radium-223 chloride), Xtandi (enzalutamide), Yervoy (ipilimumab), Zaltrap (ziv-aflibercept), Zelboraf (vemurafenib), Zevalin (ibritumomab tiuxetan), Zincard (dexrazoxane hydrochloride), ziv-aflibercept, Zoladex (goserelin acetate), zoledronic acid, Zolinza (vorinostat), Zometa (Zoledronic Acid), Zydelig (idelalisib), Zykadia (ceritinib), or Zytiga (abiraterone acetate).

[0202] In some embodiments of any of the methods described herein, the subject is human. In some embodiments, the subject is mammal. In some embodiments, the subject is veterinary animals (e.g., dogs, cats, birds, mice, horses, sheep, cattle, goats, etc.). [Examples]

[0203] Herein, refer to the following examples which non-limitingly illustrate some aspects of the present disclosure, in conjunction with the above description. Example 1 Anti-MOSPD2 antibody

[0204] Anti-MOSPD2 monoclonal antibodies were prepared according to the following method. For each antibody, heavy-chain and light-chain endotoxin-free DNA preparations were introduced into a pTXs1 expression construct. The plasmids were then transiently transfected into proprietary XtenCHO cells (80 ml culture) using a proprietary Xten transfection protocol. When viability decreased to less than 50% (14 days after transfection), samples of the culture medium were collected, and the antibodies were then purified in Protein G resin by the following standard method: (i) clarification by 0.22 μm filtration, (ii) equilibration, binding, and washing with phosphate-buffered saline (PBS) pH 7.5, (iii) elution by pH shift with Tris-glycine pH 2.7, (iv) neutralization with Tris-HCl pH 8.5, and (v) pooling of the fraction of interest and exchange of buffer with PBS pH 7.5. Yields were estimated using an Octet RED95 instrument. Purity was determined based on unreduced sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The generated antibodies are listed in Table 2. JPEG0007879612000002.jpg10582

[0205] The KD of the anti-MOSPD2 antibody was determined using a Biacore T200. Antigen (10 μg / ml) was immobilized on a CM5 sensor chip. Solutions containing the antibody at twice the concentration (1–32 nM) were flowed onto the CM5 chip. Responses captured over time indicated the progression of interaction and association / dissociation cycles. Dynamic parameters and affinity were calculated using BIAevaluation software. The obtained values ​​are listed in Table 3. JPEG0007879612000003.jpg7973 Example 2 Binding of anti-MOSPD2 antibodies to surface-expressed human MOSPD2

[0206] A study was conducted to evaluate the binding of an anti-MOSPD2 antibody (i.e., antibody S11(#8) in Table 2 of Example 1) to its undenatured form of MOSPD2 in human monocytes. For this purpose, erythrocytes were lysed from 250 μl of human peripheral blood. After staining leukocytes with an isotype control antibody or 2 μg of anti-MOSPD2 antibody, they were incubated with FITC-conjugated anti-CD14 antibody (1 μg) and secondary APC-conjugated anti-human Fcγ antibody (1:200) for gating on monocytes. Analysis was performed by flow cytometry. The results in Figure 1, gated with CD14-positive cells, show that the anti-MOSPD2 antibody binds to surface-expressed MOSPD2 on human monocytes. Example 3 Binding affinity of anti-MOSPD2 antibody

[0207] A study was conducted to determine the binding affinity profile of the anti-MOSPD2 antibody (i.e., antibody S11(#8) in Table 2 of Example 1). For this purpose, human MOSPD2 (10 μg / ml) was immobilized on a CM5 sensor chip. 1 nM, 2 nM, 4 nM, 8 nM, and 16 nM anti-MOSPD2 antibodies were contacted on the CM5 chip, and the response was captured over time to show the progression of interaction and association / dissociation cycles. Regeneration between different antibody concentrations was performed to remove all remaining bound antibodies from the chip. Dynamic parameters and affinity were calculated using BIAevaluation software.

[0208] The results showed that the anti-MOSPD2 antibody was 9.51 × 10⁶ 5 The Ka value is 1.32 × 10⁻⁶. -3 The Kd value and 1.39 × 10 -9 The calculated KD of M indicates binding to MOSPD2. Furthermore, the sensorgram showed a smooth and consistent dose-response relationship (Figure 2). Example 4 In vitro dose-range efficacy and EC50 of anti-MOSPD2 antibodies

[0209] The efficacy of the dose range was demonstrated, with the anti-MOSPD2 antibody accounting for half of the maximum response, i.e., EC 50Experiments were conducted to determine the concentration that affects monocyte migration. SDF-1 and MCP-1 (100 ng / ml) were placed in the lower chamber of a QCM 24-well migration assay plate. Human primary monocytes (3 × 10⁶) 5 Monocytes were pre-incubated for 30 minutes with 0.01, 0.1, 0.5, 1, 5, or 10 μg / ml of anti-MOSPD2 antibody or 10 μg / ml of IgG1 control antibody. The monocytes were then seeded in the upper chamber for 3 hours, and the number of cells that migrated to the lower compartment was determined by fluorescence-activated cell sorting (FACS). The data in Figures 3A-3B demonstrate that significant inhibition of migration could be achieved at a low dose of 0.5 μg / ml. Furthermore, the EC of the antibody... 50 It was in the low nM range. Example 5 In vitro efficacy study using variants of anti-MOSPD2 antibodies

[0210] Experiments were conducted to demonstrate the effects of various anti-MOSPD2 antibodies on monocyte migration. Interstitial cell-derived factor 1 (SDF-1) and monocyte chemotactic protein-1 (MCP-1) (100 ng / ml) were placed in the lower chamber of a QCM 24-well migration assay plate. Human primary monocytes (3 × 10⁶) 5 Monocytes were pre-incubated for 30 minutes with either 10 μg / ml anti-MOSPD2 antibody or 10 μg / ml IgG1 control antibody. The monocytes were then seeded in the upper chamber for 3 hours, and the number of cells that migrated to the lower compartment was determined by FACS. The data in Figures 4A–4BB demonstrate that all tested anti-MOSPD2 antibodies significantly inhibited monocyte migration. The antibody numbering in Figures 4A–4BB corresponds to the antibody numbering in Table 2. Example 6 Anti-MOSPD2 antibodies reduce inflammation and fibrosis in HFHC NASH mouse models.

[0211] Mice were fed a high-fat, high-carbohydrate (HFHC) diet combined with water concentrated with fructose and sucrose to induce non-alcoholic steatohepatitis (NASH) for 18 weeks, or a control diet (CHOW diet). From week 10, mice were treated intraperitoneally with 500 μg of anti-MOSPD2 antibody or control antibody (control Ab) once a week for 9 weeks. After treatment, livers were collected from the mice, and samples were stained with hemotoxin and eosin (H&E) or Masson's trichomes, and histologically evaluated for the presence of fatty liver, inflammation, and fibrosis. As shown in Figure 5, treatment with anti-MOSPD2 antibody reduced inflammation and fibrosis in NASH. Example 7 Anti-MOSPD2 antibodies reduce monocyte accumulation and fibrosis in HFHC NASH mouse models.

[0212] Mice were fed a high-fat, high-carbohydrate (HFHC) diet combined with water concentrated with fructose and sucrose to induce non-alcoholic steatohepatitis (NASH) for 18 weeks, or a control diet (CHOW diet). From week 10, mice were treated intraperitoneally with 500 μg of anti-MOSPD2 antibody or control antibody (isotype control) once a week for 9 weeks. After treatment, livers were harvested from the mice and immunohistochemical staining was performed on 4 μm sections. The sections were dewaxed, pretreated with an epitope recovery solution at pH=6 for 10 minutes, and incubated with anti-CD68 antibody (1:400) for 30 minutes. The Leica Refine-HRP kit was used for detection. Histological evaluation was performed using an Olympus BX60 microscope.

[0213] The staining results are shown in Figures 6A-6C, and the percentage of fibrotic area is shown in Figure 6D. Figures 6A-6D show that anti-MOSPD2 antibodies reduced the accumulation of CD68+ cells (i.e., monocytes) and fibrosis. Example 8 Treatment with anti-MOSPD2 antibodies significantly improves disease activity in a mouse model of TNBS-induced colitis.

[0214] Colitis was induced in mice using trinitrobenzenesulfonic acid (TNBS). After 24 hours of fasting, 100 μl of a 50% ethanol solution containing 1.4% TNBS was administered rectally via a 21G diameter polyurethane catheter inserted 4 cm into the colon (day 0). The mice were then inverted for 3-4 minutes by pinching their anus and holding their tails. On days 2, 0, and 3, the mice were treated intraperitoneally with 500 μg of anti-MOSPD2 antibody or control antibody (isotype control). The disease activity index (DAI) was calculated based on the scoring method shown in Table 4. Example 9 Treatment with anti-MOSPD2 antibodies significantly improves disease activity in a mouse model of TNBS-induced colitis.

[0215] Colitis was induced in mice using trinitrobenzenesulfonic acid (TNBS). After 24 hours of fasting, 100 μl of a 50% ethanol solution containing 1.4% TNBS was administered rectally via a 21G diameter polyurethane catheter inserted 4 cm into the colon (day 0). The mice were then inverted for 3-4 minutes by pinching their anus and holding their tails. On days 2, 0, and 3, the mice were treated intraperitoneally with 500 μg of anti-MOSPD2 antibody or control antibody (isotype control). The disease activity index (DAI) was calculated based on the scoring method shown in Table 4. JPEG0007879612000004.jpg2175

[0216] At the end of the experiment, the colon 1 cm above the anus was washed and placed in a 24-well plate containing 1 ml of culture medium. The supernatant was collected and tested for cytokines by enzyme-linked immunosorbent assay (ELISA).

[0217] As shown in Figures 7 and 8A-8C, anti-MOSPD2 antibodies significantly improve colitis disease activity and reduce inflammatory mediators IL-6, MCP-1, and IL-12p40. Example 10 Anti-MOSPD2 antibodies significantly inhibit the migration of monocytes derived from RRMS patients.

[0218] SDF-1 and MCP-1 (100 ng / ml) were placed in the lower chamber of a QCM 24-well migration assay plate. Human primary monocytes (3 × 10⁶) derived from patients with relapsing-remitting multiple sclerosis (RRMS) were then added. 5 The monocytes were pre-incubated for 30 minutes with either 10 μg / ml anti-MOSPD2 monoclonal antibody (mAb) or 10 μg / ml IgG1 control antibody. The monocytes were then seeded in the upper chamber for 3 hours, and the number of cells that migrated to the lower compartment was determined by FACS.

[0219] As shown in Figure 9, anti-MOSPD2 antibodies significantly inhibit monocyte migration from RRMS patients with different activation therapies and disease severity. Example 11 Anti-MOSPD2 antibodies significantly inhibit the migration of monocytes derived from PPMS and SPMS patients.

[0220] SDF-1 and MCP-1 (100 ng / ml) were placed in the lower chamber of a QCM 24-well migration assay plate. Human primary monocytes (3 × 10⁶) derived from patients with primary progressive or secondary progressive multiple sclerosis (PPMS or SPMS, respectively) were used. 5 Monocytes were pre-incubated for 30 minutes with either 10 μg / ml anti-MOSPD2 mAb or 10 μg / ml IgG1 control antibody. The monocytes were then seeded in the upper chamber for 3 hours, and the number of cells that migrated to the lower compartment was determined by FACS. As shown in Figure 10, the anti-MOSPD2 antibody significantly inhibited monocyte migration from PPMS and SPMS patients. Example 12 Anti-MOSPD2 antibodies significantly inhibit the migration of monocytes derived from RA and PsA patients.

[0221] SDF-1 and MCP-1 (100 ng / ml) were placed in the lower chamber of a QCM 24-well migration assay plate. Human primary monocytes (3 × 10⁶) derived from patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) were used. 5 Monocytes were pre-incubated for 30 minutes with either a 10 μg / ml anti-MOSPD2 mAb or a 10 μg / ml IgG1 control antibody. The monocytes were then seeded in the upper chamber for 3 hours, and the number of cells that migrated to the lower compartment was determined by FACS. As shown in Figure 11, the anti-MOSPD2 antibody significantly inhibited monocyte migration from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Example 13 Anti-MOSPD2 antibodies significantly inhibit monocyte migration from patients with Crohn's disease and ulcerative colitis.

[0222] SDF-1 and MCP-1 (100 ng / ml) were placed in the lower chamber of a QCM 24-well migration assay plate. Human primary monocytes (3 × 10⁶) derived from patients with ulcerative colitis or Crohn's disease were then used. 5 Monocytes were pre-incubated for 30 minutes with either 10 μg / ml anti-MOSPD2 mAb or 10 μg / ml IgG1 control antibody. The monocytes were then seeded in the upper chamber for 3 hours, and the number of cells that migrated to the lower compartment was determined by FACS. As shown in Figure 12, the anti-MOSPD2 antibody significantly inhibited monocyte migration from patients with Crohn's disease and ulcerative colitis. Example 14 Binding of anti-MOSPD2 antibodies to MOSPD2 in human cancer cell lines

[0223] We conducted a study to evaluate the binding of anti-MOSPD2 antibodies to MOSPD2 expressed in human cancer cells. For this purpose, we used cervical cancer (Hela), triple-negative (TN) breast cancer (MDA-231), melanoma (A2058), and myeloid (U937) cell lines (1 × 10⁶). 6The cells were stained with an isotype control antibody or humanized anti-MOSPD2 antibody (2 μg), followed by incubation with a secondary APC conjugate anti-human Fcγ antibody (1:200). Analysis was performed by flow cytometry. The results in Figures 13A-13D show that the anti-MOSPD2 antibody binds to surface-expressed MOSPD2 in different cancer cell lines.

[0224] The following sequences in Table 5 are part of this disclosure. JPEG0007879612000005.jpg11877 JPEG0007879612000006.jpg11777JPEG0007879612000007.jpg11577JPEG0007879612000008. jpg11577JPEG0007879612000009.jpg11377JPEG0007879612000010.jpg11377JPEG0007879612 000011.jpg11577JPEG0007879612000012.jpg11577JPEG0007879612000013.jpg11577JPEG000 7879612000014.jpg11377JPEG0007879612000015.jpg11577JPEG0007879612000016.jpg10877

[0225] All publications, patents, and patent applications referenced herein are incorporated herein by reference in the same manner as each individual publication, patent, or patent application is specifically and individually indicated as being incorporated herein by reference. Furthermore, any citation or specification of references herein should not be construed as an acknowledgment that such references are available as prior art of the present invention. Section headings, insofar as they are used, should not necessarily be construed as restrictive.

Claims

1. An antibody or antigen-binding fragment thereof that specifically binds to motile sperm domain-containing protein 2 (MOSPD2), comprising the following: (i) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (ii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (iii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (iv) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 3; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (v) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (vi) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 4; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (vii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (viiii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 11; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 20; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (ix) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 5; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 12; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 21; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (x) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 6; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xi) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 6; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 14; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 23; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xi) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xiiii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 8; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xiv) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xv) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 16; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xvi) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xvii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 18; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 19; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xviiii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xix) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 2; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xx) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xxi) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 10; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xxii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xxiii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 15; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xxiv) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xxv) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 17; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; (xxvi) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 24; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO: 25; or (xxvii) Heavy chain CDR1 containing the amino acid sequence of SEQ ID NO: 1; Heavy chain CDR2 containing the amino acid sequence of SEQ ID NO: 7; Heavy chain CDR3 containing the amino acid sequence of SEQ ID NO: 9; Light chain CDR1 containing the amino acid sequence of SEQ ID NO: 13; Light chain CDR2 containing the amino acid sequence of SEQ ID NO: 22; and Light chain CDR3 containing the amino acid sequence of SEQ ID NO:

25.

2. The antibody or its antigen-binding fragment according to claim 1, wherein the antibody is a polyclonal antibody, a monoclonal antibody, or a chimeric antibody.

3. The antibody or antigen-binding fragment according to claim 1 or 2, wherein the antigen-binding fragment is Fab, Fab', F(ab')2, Fv, scFv, or a combination thereof.

4. The antibody or antigen-binding fragment according to any one of claims 1 to 3, wherein the antibody is IgG1, IgG2, IgG3, IgG4, a variant thereof, or a combination thereof.

5. Approximately 1×10 ５ (1 / Ms) ~ approx. 7×10 ６ The value of Ka (1 / Ms) is approximately 1 × 10⁻⁶. －４ Kd values ​​of (1 / s) to approximately 0.4(1 / s); and / or approximately 2 × 10⁻⁶ －１０ (M) ~ approx. 6 x 10 －８ An antibody or antigen-binding fragment according to any one of claims 1 to 4, which binds to MOSPD2 with a calculated KD of (M).

6. The antibody or antigen-binding fragment according to any one of claims 1 to 5, wherein the MOSPD2 is human MOSPD2.

7. The antibody or antigen-binding fragment according to any one of claims 1 to 6, wherein the MOSPD2 has one amino acid sequence from sequence numbers 26 to 29.

8. The antibody or antigen-binding fragment according to any one of claims 1 to 7, wherein the MOSPD2 has an amino acid sequence encoded by any one nucleic acid sequence of sequence numbers 30 to 33.

9. A nucleic acid encoding an antibody or an antigen-binding fragment thereof, as described in any one of claims 1 to 8.

10. A vector comprising the nucleic acid described in claim 9.

11. A cell containing the vector according to claim 10.

12. A method for producing an antibody or antigen-binding fragment that specifically binds to MOSPD2, comprising culturing the cells described in claim 11 under suitable conditions, and isolating the antibody or antigen-binding fragment.

13. A composition comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 8, a nucleic acid according to claim 9, a vector according to claim 10, or a cell according to claim 11, and a carrier.

14. A kit comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8, a nucleic acid according to claim 9, a vector according to claim 10, or cells according to claim 11, and instructions for use.

15. A pharmaceutical composition for treating or preventing an inflammatory disease or disorder, comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8.

16. A pharmaceutical composition for inhibiting or preventing the migration of inflammatory cells, comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8.

17. The pharmaceutical composition according to claim 16, wherein the inflammatory cells are monocytes or neutrophils.

18. A pharmaceutical composition for treating or preventing non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8.

19. A pharmaceutical composition for treating or preventing fibrosis, comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8.

20. The pharmaceutical composition according to claim 19, wherein the fibrosis is hepatic fibrosis.

21. A pharmaceutical composition for treating or preventing arthritis, comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8.

22. The pharmaceutical composition according to claim 21, wherein the arthritis is rheumatoid arthritis or psoriatic arthritis.

23. A pharmaceutical composition according to claim 21 or 22, to be used in combination with further therapeutic agents.

24. The pharmaceutical composition according to claim 23, wherein the further therapeutic agent is methotrexate, baricitinib, hydroxychloroquine, prednisone, etanercept, sulfasalazine, infliximab, adalimumab, ixekizumab, or a combination thereof.

25. A pharmaceutical composition for treating or preventing multiple sclerosis, comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8.

26. The pharmaceutical composition according to claim 25, wherein the multiple sclerosis is relapsing-remitting multiple sclerosis, primary progressive multiple sclerosis, or secondary progressive multiple sclerosis.

27. A pharmaceutical composition according to claim 25 or 26, to be used in combination with further therapeutic agents.

28. The pharmaceutical composition according to claim 27, wherein the further therapeutic agent is teriflunomide, natalizumab, dimethyl fumarate, ocrelizumab, IFNβ-1a, cladribine, glatiramer acetate, or a combination thereof.

29. A pharmaceutical composition for treating or preventing inflammatory bowel disease, comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8.

30. The pharmaceutical composition according to claim 29, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.

31. The pharmaceutical composition according to claim 30, to be used in combination with further therapeutic agents.

32. The pharmaceutical composition according to claim 31, wherein the further therapeutic agent is infliximab, vedolizumab, azathioprine, adalimumab, masalazine, or a combination thereof.

33. A pharmaceutical composition for treating or preventing cancer metastasis, comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8.

34. A pharmaceutical composition for treating or preventing cancer, comprising an antibody or antigen-binding fragment according to any one of claims 1 to 8.

35. The pharmaceutical composition according to claim 33 or 34, wherein the cancer is breast cancer, cervical cancer, melanoma, bone marrow cancer, colon cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer, thyroid cancer, or prostate cancer.

36. A pharmaceutical composition according to any one of claims 15 to 35, which is administered intravenously to a target.

37. A pharmaceutical composition according to any one of claims 15 to 35, which is administered subcutaneously to a target.

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