Invented by Kate MONROE, Helen Lam, Arnon Rosenthal, Seung-Joo Lee, Francesca AVOGADRI-CONNORS, William MONTEITH, Alector LLC

The Market for Anti-Siglec-7 Antibodies and Their Use Antibodies are an essential tool in biomedical research and have revolutionized the field of medicine. They are widely used in diagnostics, therapeutics, and research applications. One such antibody gaining attention in recent years is the anti-Siglec-7 antibody. Siglec-7, short for sialic acid-binding immunoglobulin-like lectin 7, is a protein found on the surface of certain immune cells. The market for anti-Siglec-7 antibodies is rapidly growing, driven by their potential in cancer immunotherapy and autoimmune disease research. Siglec-7 is primarily expressed on natural killer (NK) cells, a type of white blood cell that plays a crucial role in the immune system’s defense against cancer and viral infections. It acts as an inhibitory receptor, regulating NK cell activity and preventing excessive immune responses. However, in certain diseases, such as cancer and autoimmune disorders, Siglec-7 can be overexpressed, leading to immune dysfunction. This has sparked interest in developing anti-Siglec-7 antibodies as a therapeutic approach. In cancer immunotherapy, anti-Siglec-7 antibodies have shown promise in enhancing the activity of NK cells against tumor cells. By blocking the inhibitory signal from Siglec-7, these antibodies can unleash the full potential of NK cells, leading to improved tumor cell killing. Several preclinical studies have demonstrated the efficacy of anti-Siglec-7 antibodies in various cancer models, including breast cancer, leukemia, and melanoma. These findings have paved the way for clinical trials to evaluate the safety and efficacy of these antibodies in cancer patients. Furthermore, anti-Siglec-7 antibodies have also found utility in autoimmune disease research. In conditions like rheumatoid arthritis and multiple sclerosis, aberrant immune responses contribute to tissue damage and inflammation. By targeting Siglec-7, researchers aim to modulate the activity of NK cells and restore immune balance. Early studies have shown promising results, suggesting that anti-Siglec-7 antibodies could be a potential therapeutic option for these diseases. The market for anti-Siglec-7 antibodies is witnessing significant growth due to the increasing demand for innovative immunotherapies and the rising prevalence of cancer and autoimmune disorders. Pharmaceutical companies and biotechnology firms are actively investing in research and development to develop novel anti-Siglec-7 antibodies. The market is highly competitive, with several players striving to develop antibodies with improved efficacy, specificity, and safety profiles. In addition to therapeutic applications, anti-Siglec-7 antibodies are also valuable research tools. They enable scientists to study the role of Siglec-7 in immune regulation, investigate its interactions with other molecules, and explore its potential as a biomarker for disease diagnosis and prognosis. The availability of high-quality anti-Siglec-7 antibodies is crucial for advancing our understanding of immune responses and developing targeted therapies. In conclusion, the market for anti-Siglec-7 antibodies is expanding rapidly, driven by their potential in cancer immunotherapy and autoimmune disease research. These antibodies hold promise in enhancing the activity of NK cells against tumors and modulating immune responses in autoimmune disorders. As research progresses and clinical trials unfold, anti-Siglec-7 antibodies may emerge as a valuable addition to the arsenal of immunotherapies, improving patient outcomes and transforming the treatment landscape for cancer and autoimmune diseases.

The Alector LLC invention works as follows

The present disclosure is directed towards compositions containing antibodies (e.g. monoclonal antibodies, chimeric antibodies, humanized antibodies etc.) that bind to or more epitopes on a Siglec-7 proteins, such as human Siglec-7 and mammalian Siglec-7. It also includes the use of these compositions for preventing, treating or reducing risks.

Background for Anti-Siglec-7 antibodies, and their use.

Sialic Acid-binding Iglike Lectin-7 (Siglec-7)” is a type 1 immunoglobulin like transmembrane expressed on immune and hemopoietic cell types, including immature or mature myeloid, such as neutrophils and mast cells. It also appears in lymphoid, such natural killer cells and T-cell subsets (Crocker and al. (2007) Nat Rev Immunol. Angata and Varki (2000, Glycobiology 10, 4: 431-438) 7:255-266 Nicoll et al (1999) JBC 274:48: 34089-34095; Falco et al. (1999) J. Exp. Med. 190: 793-802). Siglec-7 belongs to the Siglec family, a group of lectins which binds sialic acids in glycoproteins and lipids. Siglec proteins can bind to gangliosides, which are glycolipids consisting of a ceramide and a sialylated Glycan. The majority of gangliosides have a lacto-ceramide central core, and may contain one or more residues of sialic acids. The diversity in Siglec ligands can be generated by adding other neutral sugars, sialic acids in different linkages and modifications of sialic Acid itself.

The sialic-binding region is located on the V-set Ig-like domain, which contains two aromatic residues and one arginine motif highly conserved in all Siglecs (Crocker et al. The sialic-acid-binding site is found on the V set Ig-like region, which contains two aromatic residues as well as one arginine motif that are highly conserved among all Siglecs. (2007) Nat Rev Immunol. McMillan & Crocker (2008) Carbohydr Res. 343:2050-2056; Von Gunten and Bochner (2008) Ann NY Acad Sci. 1143:61-82; May et al. Mol Cell. 1:719-728; Crocker et al. (1999) Biochem J. Crocker and Varki, Trends Immunol. 2:337-342). Crystal structures of ligands with and without sialylation have been used to map the binding sites. Chem. 278:5: 3372-3377; Attrill et al., (2006) J. Biol. Chem. Chem. 1R-27R). Siglecs bind ligands in both trans and cis, depending on whether the cell membrane is rich in sialic acid. This affects their functional properties. Each Siglec prefers to bind the different types of sialylated glycocans found on the surfaces of mammalian cell (Crocker and al. (2007) Nat Rev Immunol. 7:255-266; and Crocker et al. (2007) Nat Rev Immunol. 7:255-266). The majority of Siglec proteins including Siglec-7 contain immunoreceptor-based inhibitory motif sequences (ITIMs) in their cytoplasmic ends, which allows them to be inhibitory receptors as well as negative regulators of immunity through recruitment of tyrosine and phosphatase SHP1 andSHP2 (Crocker and al.). (2007) Nat Rev Immunol. McMillan & Crocker (2008) Carbohydr Res. McMillan and Crocker (2008) Carbohydr Res. 1143:61-82). The Siglec protein family is associated with multiple human diseases including autoimmunity, susceptibility to infection, multiple types of cancer, including lymphoma, leukemia and acute myeloid leukemia, systemic lupus erythematosus, rheumatoid arthritis, neurodegenerative disorders, asthma, allergy, sepsis, chronic bronchitis, graft-versus-host disease, eosinophilia, and osteo “The Siglec family of proteins is linked to a variety of human diseases, including autoimmunity and susceptibility for infection. They are also associated with cancers such as lymphoma and leukemia (including acute myeloid), rheumatoid and neurodegenerative diseases, as well as asthma, allergy, sepsis and chronic obstructive lung disease.

Siglec-7 has been cloned since 1999 (Falco and others) (1999) J. Exp. Med. Med. (1999) J. Exp. Med. 190: 793-802).

Siglec-7 contains an extracellular N-terminal Ig-like (immunoglobulin-like) V-type domain, two Ig-like C2-set domains as well as one consensus ITIM motif and a non-conforming membrane-distal ITIM-like motif in its cytoplasmic domain. Siglec-7 binds red blood cells with a sialic-dependent manner, as shown by the loss of binding after sialidase treatment. Angata & Varki (2000) Glycobiology, 10:4:431-438) suggest that the binding is mediated by sialic acid?2-3 and?2-6 linkages. Siglec-7 binds to?2-8 dialyls with a 10 nM affinity. It also shows a higher affinity towards branched 2-6 sialyls than terminal 2-3 or sialic acid linkages (Yamaji, J. Biol. Chem. 277:8 6324-6332). In vivo, Siglec-7 ligands can be expressed on b series gangliosides, such as GD2, GD3, GT1b and GD3b. These b-series gangliosides are found in cells of the central nerve system, melanoma and T cell subsets (Urmacher et. al. (1989) Am. J. Dermatopathol. 11: 577-581, Kniep et al. (1993) Blood, 82:1776-1786. The high resolution crystal structure of Siglec-7’s N-terminal V set Ig-like region suggests that the ligand-binding specificity of Siglec members is located in the variable C? (Alphey et. al. (2003) J. Biol. Chem 278 (3372-3377).

Siglec-7 undergoes the phosphorylation Tyr-437 and Tyr-460, by tyrosine Kinases likely c-Src, or Lck” (Avril, et. al., J. Imm. 173: 6841-6849). After phosphorylation on Tyr-437 of the ITIM domains (mostly proximal, but also distal Tyr-460), Siglec-7 binds to SHP-2/PTPN11 and PTPN6. 173: 6841-6849). Phosphatase is linked to decreased intracellular calcium mobilisation and decreased tyrosine-phosphorylation of multiple proteins. (Ulyanova T. et. al. (1999) Eur J Immunol 29: 3440-34449; Paul S. P. et. al. (2000). Blood 96, 483, 490), as well as blockade of immune response and signal transduction, in part through dephosphorylation on adjacent activating molecules, including those containing ITAM motifs.

Some, but not all Siglec-ligands cause receptor downregulation” (Macauley, S. M. et. al., 2014 Nature Reviews Immunology, 14, 653-666). There have been reports of receptor degradation caused by ligands for tyrosine kinase (Monsonego Oran et. al. (2002) Febs Letters 528, 83 – 89; and Fasen et. al. (2008) Cell & Molecular Biology 9). 251-266), as well as steroid receptors (Callige et al., (2005) Mol. Cell. Biol. 25. 164, 49-59). 164, 49-59). It has been demonstrated that Suppressor Of Cytokine Signaling 3 (SOCS3) competes with SHP-12 and binds Siglec-7 in the presence Siglec-7 Crosslinking upon ITIM Phosphorylation (Orr et. al. (2007) J. Biol. Chem. 282: 3418-3422). The SOCS3-ECS E3 ligase binding leads to the targeting of Siglec-7 by ECS E3 for proteasome degradation (Williams and Palmer, 2012 Biochem. Soc. Trans. 40: 215-218; Orr et al. (2007) J. Biol. Chem. 282: 3418-3422).

Activation Siglec-7 Signaling is also associated with an increased production of proinflammatory cytokines IL-6, IL-1alpha, MIP-1beta, IL-8, and TNFalpha as well as selective upregulation of adhesion molecule ICAM-1 and CD49e in human monoocytes” (Varchetta et.al. (2012) PLOS One 7: 9: e45821). These activities of Siglec-7 seem to be mediated by the phosphorylation ERK (Varchetta et. al. (2012) PLOS One 7: 9: e45821). “It has been suggested that the association between ITIM containing Siglec and activating receptors could be mediated through extracellular ligands which bind and bridge receptors. (Macauley, S. M. and al. (2014) Nature Reviews Immunology 14: 653-666).

Multiple studies suggest that Siglec-7 plays an inhibitory role in the function of natural killers, in T-cell receptor signaling and in attenuating signaling by DCs” (Crocker, et. al. (2012) Ann. N Y Acad. Sci. 1253, 102-111; Pillai et al., (2012) Annu. Rev. Immunol. 30, 357-392; von Gunten and Bochner (2008) Ann. N Y Acad. Sci. 1143, 61-82; Ikehara et al. (2004) J. Biol. Chem. 279:41 43117-43125; Nicoll et al. (2003) Eur. J. Imm. 33:6:1642-1648; Hudak et al. (2013) Nat. Chem. Biol. ; Bax et al. (2007) J. Imm 179: 12: 8216-8224; Lock et al. (2004) Immunobiology 209. 1-2:199 – 207. Functional studies on natural killer cells showed that tumor cells expressing Siglec-7-binding sialic acids inhibited NK cell activation, and the killing of tumor cells. Sialic acid-binding ligands are upregulated in many human tumors. This allows immune evasion, and can lead to cancer progression. (2014) J. Clinic. Invest. 124:4: 1810-1820). Moreover, Hudak et al. Using glycocalyx, Hudak et al. showed that cells coated in synthetic sialoside polymers were protected against NK cytotoxicity. The upregulation of sialic acids in tumors is thought to facilitate a state called “super self”. This inhibits the immune surveillance of natural killer cells (Macauley & Paulson, 2014 Nat. Chem. Biol. 10:1: 7-8).

The closest Siglec is mouse Siglec E, which is 53% identical to Siglec-7. Genetic inactivation does not cause obvious behavioral, developmental or histological abnormalities in mice. Siglec-E-deficient animals also breed normally. This suggests that Siglec-E may not be an essential gene, and its function is likely to be limited to the innate immune system (McMillan and colleagues). (2013) Blood 121:11 : 2084-2094. After aerosol LPS was sprayed on mice deficient in Siglec E, an increased recruitment of neutrophils to the lung could be seen. This recruitment could be reversed with the blockade the?2-integrin CD11b. Siglec E deficient neutrophils showed increased phosphorylation in a CD11b dependent manner of Syk, p38 MAPK and Syk. These data suggest that Siglec E functions to suppress neutrophil recruiting in a lung inflammation model (McMillan and al. “(2013 Blood 121:11 : 2084-2094).

Crosslinking Siglec-7 was shown to inhibit cellular proliferation in oncology (Vitale and al.). (1999) PNAS 96: 15091-15096; Vitale et al. (2001) PNAS: 10: 5764-5769). Siglec-7 inhibits cytokine-induced cell proliferation (Orr and al. (2007) J. Biol. Chem. 282: 3418-3422).

Antibodies against Siglec-7 are described, for instance, in WO2011038301 by Jandus and co-workers. (2014) J. Clinical Invest. 124:4: 1810-1820, Varchetta et al. (2012) PLOS One 7: 9: e45821 et al. (2012). Falco et al. (1999) J. Exp. Med. 190: 793-802, Nicoll et al (1999) JBC 274:48: 34089-34095, Nicoll et al. (2003) Eur. J. Imm. 33: 1642-1648. These antibodies, however, do not have the functional properties required to be a therapeutic antigen.

Accordingly, there is an urgent need for therapeutic antibodies which bind Siglec-7 specifically and reduce Siglec-7’s expression on the surface of cells, reduce interactions between Siglec-7 with one or several Siglec-7-ligands and/or reduce Siglec-7’s activities to treat diseases, disorders and conditions that are associated with unwanted Siglec-7 activity.

All references, including publications, patents and patent applications, are hereby included by reference.

The ” This The

Certain aspects of the disclosure are based at least in part on the identification anti-Siglec-7 antibody that is capable of reducing cell surface levels Siglec-7 of human primary immune cell and Siglec-7 expression cell lines, and/or inhibiting the binding Siglec-7 Ligands to Siglec-7. (See, for example, Examples 3-5).

Accordingly, certain aspects relate to an isolated monoclonal anti -Siglec-7 antibodies, wherein said anti-Siglec-7 antibodies decrease cellular levels Siglec-7. In certain embodiments, anti-Siglec-7 antibodies decrease cellular levels without inhibiting the interaction between Siglec-7 with one or more Siglec-7 Ligands. In some embodiments the antibody inhibits further interaction between Siglec-7 with one or more Siglec-7 Ligands.

The present disclosure also includes an isolated monoclonal anti -Siglec-7 antibody, which decreases the cellular level of Siglec-7 while inhibiting the interaction between Siglec-7 with one or more Siglec-7 Ligands.

In In In Anti The The The Repeat The TREM2, Sirp beta, FcgR, DAP10, and DAP12; (bb) inhibition of signaling by one or more pattern recognition receptors (PRRs), optionally wherein the one or more PRRs are selected from receptors that identify pathogen-associated molecular patterns (PAMPs), receptors that identify damage-associated molecular patterns (DAMPs), and any combination thereof; (cc) inhibition of one or more receptors comprising the motif D/Ex0-2 YxxL/IX6-8 YxxL/I (SEQ ID NO: 537); (dd) inhibition of signaling by one or more Toll-like receptors; (ee) inhibition of the JAK-STAT signaling pathway; (ff) inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF?B); (gg) de-phosphorylation of an ITAM motif containing receptor; (hh) modulated expression of one or more inflammatory receptors, optionally wherein the one or more inflammatory receptors comprise CD86 and the one or more inflammatory receptors are expressed on one or more of microglia, macrophages, neutrophils, NK cells, dendritic cells, bone marrow-derived dendritic cells, neutrophils, T cells, T helper cells, or cytotoxic T cells; (ii) increasing expression of one or more Siglec-7-dependent genes; (jj) normalization of disrupted Siglec-7-dependent gene expression; (kk) decreasing expression of one or more ITAM-dependent genes, optionally wherein the one more ITAM-dependent genes are activated by nuclear factor of activated T cells (NFAT) transcription factors; (11) promoting differentiation of one or more of immunosuppressor dendritic cells, immunosuppressor macrophages, immunosuppressor neutrophils, immunosuppressor NK cells, myeloid derived suppressor cells, tumor-associated macrophages, tumor-associated neutrophils, tumor-associated NK cells, and regulatory T cells; (mm) promoting or rescuing functionality of one or more of immunosuppressor dendritic cells, immunosuppressor macrophages, immunosuppressor neutrophils, immunosuppressor NK cells, myeloid-derived suppressor cells, tumor-associated macrophages, tumor-associated neutrophils, tumor-associated NK cells, and regulatory T cells; (nn) increasing infiltration of one or more of immunosuppressor dendritic cells, immunosuppressor macrophages, immunosuppressor neutrophils, immunosuppressor NK cells, myeloid-derived suppressor cells, tumor-associated macrophages, tumor-associated neutrophils, tumor-associated NK cells, and regulatory T cells into tumors; (oo) increasing the number of tumor-promoting myeloid/granulocytic immune-suppressive cells in a tumor, in peripheral blood, or other lymphoid organ; (pp) enhancing tumor-promoting activity of myeloid-derived suppressor cells; (qq) increasing expression of tumor-promoting cytokines in a tumor or in peripheral blood, optionally wherein the tumor-promoting cytokines are TGF-beta or IL-10; (rr) increasing tumor infiltration of tumor-promoting FoxP3+ regulatory T lymphocytes; (ss) enhancing tumor-promoting activity of myeloid-derived suppressor cells (MDSC); (tt) decreasing activation of tumor-specific T lymphocytes with tumor killing potential; (uu) decreasing infiltration of tumor-specific NK cells with tumor killing potential; (vv) decreasing the tumor killing potential of NK cells; (ww) decreasing infiltration of tumor-specific B lymphocytes with potential to enhance immune response; (xx) decreasing infiltration of tumor-specific T lymphocytes with tumor killing potential; (yy) increasing tumor volume; (zz) increasing tumor growth rate; (aaa) increasing metastasis; (bbb) increasing rate of tumor recurrence; (ccc) decreasing efficacy of one or more immune-therapies that modulate anti-tumor T cell responses, optionally wherein the one or more immune-therapies are immune-therapies that target one or more target proteins selected from PD1/PDL1, CD40, OX40, ICOS, CD28, CD137/4-1BB, CD27, GITR, PD-L1, CTLA4, PD-L2, PD-1. Normal Some In S The In ( Si In In In In

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Other aspects of the present disclosure relate to an isolated monoclonal anti-Siglec-7 antibody, wherein the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 39-353, 39-149, 93-104, 95-105, 39-122, 123-149, 150-233, 240-336, 264-273, 295-306, 327-341, or 337-353 of SEQ ID NO: 1; or within amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 39-353, 39-149, 93-104, 95-105, 39-122, 123-149, 150-233, 240-336, 264-273, 295-306, 327-341, or 337-353 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues selected from the group consisting of: i. amino acid residues 60-69 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 60-69 of SEQ ID NO: 1; ii. amino acid residues 60-69 and 84-95 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 60-69 and 84-95 of SEQ ID NO: 1; iii. amino acid residues 60-69 and 117-127 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 60-69 and 117-127 of SEQ ID NO: 1; iv. amino acid residues 68-78 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 68-78 of SEQ ID NO: 1; v. amino acid residues 84-95 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 84-95 of SEQ ID NO: 1; vi. amino acid residues 111-122 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 111-122 of SEQ ID NO: 1; vii. amino acid residues 111-122 and 282-291 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 111-122 and 282-291 of SEQ ID NO: 1; viii. amino acid residues 113-123 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 113-123 of SEQ ID NO: 1; ix. amino acid residues 113-125 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 113-125 of SEQ ID NO: 1; x. amino acid residues 117-127 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 117-127 of SEQ ID NO: 1; and xi. amino acid residues 282-291 of SEQ ID NO: 1, or amino acid residues on a mammalian Siglec-7 protein corresponding to amino acid residues 282-291 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 60-69 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 60-69 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 60-69 and 84-95 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 60-69 and 84-95 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 60-69 and 117-127 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 60-69 and 117-127 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 68-78 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 68-78 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 84-95 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 84-95 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 111-122 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 111-122 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 111-122 and 282-291 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 111-122 and 282-291 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 113-123 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 113-123 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 113-125 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 113-125 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 117-127 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 117-127 of SEQ ID NO: 1. In some embodiments that may be combined with any of the preceding embodiments, the anti-Siglec-7 antibody binds to one or more amino acids within amino acid residues 282-291 of human Siglec-7 (SEQ ID NO: 1), or within amino acid residues on a Siglec-7 homolog or ortholog corresponding to amino acid residues 282-29 of SEQ ID NO: 1. Other aspects of the present disclosure relate to an isolated monoclonal anti-Siglec-7 antibody, wherein the anti-Siglec-7 antibody binds to one or more amino acid residues selected from the group consisting of M30, Q31, V44, R45, S47, F48, Y50, I72, W74, N81, T103, K104, T107, and R124 of SEQ ID NO: 1, or one or more amino acid residues on a mammalian Siglec-7 protein corresponding to an amino acid residue selected from the group consisting of M30, Q31, V44, R45, S47, F48, Y50, 172, W74, N81, T103, K104, T107, and R124 of SEQ ID NO: 1.

The present disclosure also relates to an isolated monoclonal anti Siglec-7 antibody, which comprises a light-chain variable domain and a heavier-chain variable domain. This anti-Siglec-7 antibody contains at least two, three or four HVRs, selected from the HVRs-L1, L2, HVRs-L3, and HVRs-H1, of a monoclonal antigen selected from the following: 1A12; 1E8; 2G1; 2G4

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