Anti-SIGLEC-7 antibodies and methods of use thereof

Abstract

The present invention relates to anti-SIGLEC-7 antibodies and methods of use thereof. The present disclosure relates generally to compositions comprising antibodies, such as monoclonal antibodies, chimeric antibodies, humanized antibodies, antibody fragments, and the like, that specifically bind to one or more epitopes within a Siglec-7 protein, such as human Siglec-7 or mammalian Siglec-7, and have improved and / or enhanced functional characteristics; and the use of such compositions for preventing, reducing the risk of, or treating a subject in need thereof.

Description

[0001] This application is a divisional application of the invention application with the application date of June 7, 2019, Chinese application number 201980050499.8, and invention name “Anti-SIGLEC-7 Antibodies and Methods of Use Thereof”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Application No. 62 / 682,439, filed June 8, 2018, which is hereby incorporated by reference in its entirety.

[0004] Submission of sequence listings as ASCII text files

[0005] The following submission in the form of an ASCII text file is incorporated herein by reference in its entirety: Computer Readable Form (CRF) of a Sequence Listing (File Name: 735022002340SEQLIST.TXT, Record Date: June 3, 2019, Size: 43KB). Technical Field

[0006] The present disclosure relates to anti-Siglec-7 antibodies and therapeutic uses of such antibodies. Background Art

[0007] Sialic acid-binding Ig-like lectin-7 (Siglec-7) is a type 1 immunoglobulin-like transmembrane protein expressed on immune and hematopoietic cells, including immature and mature myeloid cells such as monocytes, macrophages, dendritic cells, neutrophils, mast cells and microglia, as well as lymphocytes such as natural killer cells and T cell subsets (Crocker et al. (2007) Nat Rev Immunol. 7:255–266; Angata and Varki (2000) Glycobiology 10:4:431-438; Nicoll et al. (1999) JBC 274:48:34089-34095; Falco et al. (1999) J. Exp. Med. 190:793-802).

[0008] Siglec-7 contains an extracellular N-terminal Ig-like (immunoglobulin-like) V-type domain, two Ig-like C2-group domains, and a consensus ITIM motif and an inconsistent membrane distal ITIM-like motif (in its cytoplasmic domain). Due to the loss of binding after sialidase treatment, Siglec-7 was shown to bind to red blood cells in a sialic acid-dependent manner. The binding is thought to be mediated by α2-3 or α2-6 sialic acid linkages (Nicoll et al. (1999) JBC 274:48:34089-34095; Angata and Varki (2000) Glycobiology 10:4:431-438). Further studies revealed that Siglec-7 binds more efficiently to α2-8 disialyl residues (with an affinity of 10 nM) and exhibits a higher affinity for branched α2-6 sialic acid residues than for terminal α2-3 or α2-6 sialic acid residues (Yamaji (2002) J. Biol. Chem. 277:8 6324-6332). In vivo, Siglec-7 ligands are expressed on b-series gangliosides such as GD2, GD3, and GT1b, which can be found in central nervous system cells, melanoma cells, 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 the N-terminal V-group Ig-like domain of Siglec-7 revealed that the ligand-binding specificity of Siglec family members resides in the variable C-C' loop (Alphey et al. (2003) J. Biol. Chem 278:5 3372-3377).

[0009] Several studies have demonstrated an inhibitory role for Siglec-7 in natural killer cell function, regulation of T cell receptor signaling, and attenuation of signaling in DCs (Crocker et al. (2012) Ann. NY Acad. Sci. 1253, 102–111; Pillai et al. (2012) Annu. Rev. Immunol. 30, 357–392; von Gunten and Bochner (2008) Ann. NY 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 have demonstrated that tumor cells expressing Siglec-7 that bind sialic acid ligands inhibit NK cell activation and tumor cell killing. Many human tumors robustly upregulate sialic acid ligands, which enables immune evasion and cancer progression (Jandus et al. (2014) J. Clinic. Invest. 124:4:1810-1820). In addition, Hudak et al. performed glycocapsule engineering and showed that cells coated with synthetic sialoside sugar polymers protected from NK cell toxicity. It has been proposed that upregulation of sialic acid on tumors promotes a "super-self" state that strongly inhibits natural killer cell immune surveillance (Macauley and Paulson (2014) Nat. Chem. Biol. 10:1:7-8).

[0010] There is no obvious mouse homolog of Siglec-7; however, mouse Siglec-E is 53% similar and is therefore the most closely related Siglec. In mice, genetic inactivation of Siglec-E does not lead to obvious developmental, histological or behavioral abnormalities; and Siglec-E-deficient mice reproduce normally, indicating that Siglec-E is not an essential gene and its function may be limited to innate immunity (McMillan et al. (2013) Blood 121:11:2084-2094). After challenging Siglec-E-deficient mice with aerosol LPS, increased neutrophil recruitment in the lungs was demonstrated, which could be reversed by blocking the β2-integrin CD11b. Siglec-E-deficient neutrophils showed increased phosphorylation of Syk and p38 MAPK in a CD11b-dependent manner. These data suggest that Siglec-E suppresses neutrophil recruitment in a model of acute lung inflammation (McMillan et al. (2013) Blood 121:11:2084-2094).

[0011] In oncology, Siglec-7 has been considered a therapeutic target for chronic and acute myeloid leukemias because cross-linking Siglec-7 inhibits cell proliferation (Vitale et al. (1999) PNAS 96:15091-15096; Vitale et al. (2001) PNAS 98:10:5764-5769). Siglec-7 activity has also been shown to inhibit cytokine-induced cell proliferation (Orr et al. (2007) J. Biol. Chem. 282:3418-3422).

[0012] Antibodies against Siglec-7 have been described in, for example, WO2011038301; Jandus et al. (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. However, these antibodies do not exhibit the functional characteristics required for therapeutic antibodies.

[0013] Therefore, there is a need for therapeutic antibodies that specifically bind to Siglec-7 and reduce Siglec-7 expression on the cell surface, reduce the interaction between Siglec-7 and one or more Siglec-7 ligands, and / or reduce one or more Siglec-7 activities in order to treat one or more diseases, disorders, and conditions associated with undesirable Siglec-7 activity.

[0014] All references cited herein, including patents, patent applications, and publications, are hereby incorporated by reference in their entirety. Summary of the Invention

[0015] The present disclosure generally relates to compositions comprising antibodies, such as monoclonal antibodies, chimeric antibodies, humanized antibodies, antibody fragments, etc., that specifically bind to human Siglec-7; and methods of using such compositions.

[0016] Certain aspects of the present disclosure are based, at least in part, on the identification of anti-Siglec-7 antibodies with improved and / or enhanced functional characteristics (e.g., relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62). Certain aspects of the present disclosure are based, at least in part, on the identification of anti-Siglec-7 antibodies with improved and / or enhanced functional characteristics (improved and / or enhanced ability to reduce cell surface levels of Siglec-7 on human primary immune cells) and / or with improved and / or enhanced binding kinetics (e.g., relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a K for human Siglec-7 that is at least 100-fold lower than an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. D In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a K for human Siglec-7 that is at least 5.3 times lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. D .

[0017] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure are expressed in vitro with an EC of at least about 50% lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62. 50 Reducing cell surface levels of Siglec-7. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have an EC of at least about 10% lower in vitro than an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50, as measured by flow cytometry. 50 Reduce the cell surface level of Siglec-7. In some embodiments, as measured by flow cytometry, the antibody is at least 4.2 times more potent than an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62; or at least 1.4 times more potent than an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. Advantageously, the anti-Siglec-7 antibody is effective in vitro at a half-maximal effective concentration (EC) in the range of about 33.2 pM to about 25.4 nM. 50 ) reduces the cellular level of Siglec-7, binds to human cells (such as human primary dendritic cells), and has a dissociation constant (K) for human Siglec-7 in the range of about 124 nM to about 1 pM D ).

[0018] Thus, in one aspect, the present disclosure relates to an antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises: HVR-H1, wherein the HVR-H1 comprises the sequence according to Formula I: GYAFTX1X2WMN (SEQ ID NO: 6), wherein X1 is E, M, G or A, and X2 is T, A or Y; HVR-H2, wherein the HVR-H2 comprises the sequence according to Formula II: RIFPGX1GHTN (SEQ ID NO: 9), wherein X1 is L or Y; and HVR-H3, wherein the HVR-H3 comprises the sequence of DYSDYYFDY (SEQ ID NO: 10).

[0019] In another aspect, the present disclosure relates to an antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the light chain variable region comprises: HVR-L1 comprising a sequence according to Formula III: RX1SX2DX3NTYLN (SEQ ID NO: 15), wherein X1 is G or A, X2 is Q or E, and X3 is I, T, or A; HVR-L2 comprising a sequence according to Formula III: YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising a sequence according to Formula IV: QX1GX2X3X4PWT (SEQ ID NO: 24), wherein X1 is Q or G, X2 is N or G, X3 is L, T, V, or I, and X4 is L or K; and wherein the antibody is not an antibody comprising a light chain variable region comprising: an antibody comprising RASQDINTYLN (SEQ ID NO: 16). NO: 65), HVR-L1 comprising the sequence of YTSRLHS (SEQ ID NO: 16), and HVR-L3 comprising the sequence of QQGNTLPWT (SEQ ID NO: 20).

[0020] In another aspect, the present disclosure relates to an antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises: HVR-H1, wherein the HVR-H1 comprises a sequence according to Formula I: GYAFTX1X2WMN (SEQ ID NO: 6), wherein X1 is E, M, G, or A, and X2 is T, A, or Y; HVR-H2, wherein the HVR-H2 comprises a sequence according to Formula II: RIFPGX1GHTN (SEQ ID NO: 9), wherein X1 is L or Y; and HVR-H3, wherein the HVR-H3 comprises a sequence of DYSDYYFDY (SEQ ID NO: 10); and the light chain variable region comprises: HVR-L1, wherein the HVR-L1 comprises a sequence according to Formula III: RX1SX2DX3NTYLN (SEQ ID NO:15), wherein Xi is G or A, X2 is Q or E, and X3 is I, T or A; HVR-L2, said HVR-L2 comprising the sequence of YTSRLHS (SEQ ID NO:16); and HVR-L3, said HVR-L3 comprising the sequence according to Formula IV: QX1GX2X3X4PWT (SEQ ID NO:24), wherein Xi is Q or G, X2 is N or G, X3 is L, T, V or I, and X4 is L or K.

[0021] In another aspect, the present disclosure relates to an antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises: HVR-H1, wherein the HVR-H1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5; HVR-H2, wherein the HVR-H2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 7-8; and HVR-H3, wherein the HVR-H3 comprises an amino acid sequence of SEQ ID NO: 10; and the light chain variable region comprises: HVR-L1, wherein the HVR-L1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 11-14; HVR-L2, wherein the HVR-L2 comprises an amino acid sequence of SEQ ID NO: 16; and HVR-L3, wherein the HVR-L3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 17-23. In some embodiments, an anti-Siglec-7 antibody comprises HVR-H1 comprising the amino acid sequence GYAFTMAWMN (SEQ ID NO: 2); HVR-H2 comprising the amino acid sequence RIFPGYGHTN (SEQ ID NO: 8); HVR-H3 comprising the amino acid sequence DYSDYYFDY (SEQ ID NO: 10); HVR-L1 comprising the amino acid sequence RGSQDINTYLN (SEQ ID NO: 11); HVR-L2 comprising the amino acid sequence YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising the amino acid sequence QQGNLLPWT (SEQ ID NO: 17). In some embodiments, an anti-Siglec-7 antibody comprises HVR-H1 comprising the amino acid sequence GYAFTGYWMN (SEQ ID NO: 3); HVR-H2 comprising the amino acid sequence RIFPGLGHTN (SEQ ID NO: 7); HVR-H3 comprising the amino acid sequence DYSDYYFDY (SEQ ID NO: 10); HVR-L1 comprising the amino acid sequence RGSQDTNTYLN (SEQ ID NO: 12); HVR-L2 comprising the amino acid sequence YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising the amino acid sequence QQGNTLPWT (SEQ ID NO: 20).In some embodiments, an anti-Siglec-7 antibody comprises HVR-H1 comprising the amino acid sequence GYAFTGYWMN (SEQ ID NO: 3); HVR-H2 comprising the amino acid sequence RIFPGLGHTN (SEQ ID NO: 7); HVR-H3 comprising the amino acid sequence DYSDYYFDY (SEQ ID NO: 10); HVR-L1 comprising the amino acid sequence RGSQDINTYLN (SEQ ID NO: 11); HVR-L2 comprising the amino acid sequence YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising the amino acid sequence QQGNILPWT (SEQ ID NO: 23). In some embodiments, an anti-Siglec-7 antibody comprises HVR-H1 comprising the amino acid sequence GYAFTAAWMN (SEQ ID NO:4); HVR-H2 comprising the amino acid sequence RIFPGLGHTN (SEQ ID NO:7); HVR-H3 comprising the amino acid sequence DYSDYYFDY (SEQ ID NO:10); HVR-L1 comprising the amino acid sequence RGSQDINTYLN (SEQ ID NO:11); HVR-L2 comprising the amino acid sequence YTSRLHS (SEQ ID NO:16); and HVR-L3 comprising the amino acid sequence QQGNILPWT (SEQ ID NO:23).

[0022] Other aspects of the present disclosure relate to an antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a Kabat CDR; and / or the light chain variable region comprises a Kabat CDR. In some embodiments, the heavy chain variable region comprises CDR-H1, wherein the CDR-H1 comprises the sequence of GYAFTAAWMN (SEQ ID NO: 4); CDR-H2, wherein the CDR-H2 comprises the sequence of RIFPGLGHTN (SEQ ID NO: 7); and CDR-H3, wherein the CDR-H3 comprises the sequence of DYSDYYFDY (SEQ ID NO: 10). In some embodiments, the light chain variable region comprises a CDR-L1 comprising the sequence of RGSQDINTYLN (SEQ ID NO: 11); a CDR-L2 comprising the sequence of YTSRLHS (SEQ ID NO: 16); and a CDR-L3 comprising the sequence of QQGNILPWT (SEQ ID NO: 23). In some embodiments, the heavy chain variable region comprises CDR-H1 comprising the sequence of GYAFTAAWMN (SEQ ID NO:4); CDR-H2 comprising the sequence of RIFPGLGHTN (SEQ ID NO:7); and CDR-H3 comprising the sequence of DYSDYYFDY (SEQ ID NO:10); and the light chain variable region comprises CDR-L1 comprising the sequence of RGSQDINTYLN (SEQ ID NO:11); CDR-L2 comprising the sequence of YTSRLHS (SEQ ID NO:16); and CDR-L3 comprising the sequence of QQGNILPWT (SEQ ID NO:23).

[0023] In some embodiments that may be combined with any of the preceding embodiments, the heavy chain variable region comprises one, two, three, or four framework regions selected from VH FR1, VH FR2, VH FR3, and VH FR4, wherein: VH FR1 comprises the sequence QVQLVQSGAEVKKPGASVKVSCKAS (SEQ ID NO: 25); VH FR2 comprises the sequence according to Formula V: WVRQAX1GQX2LEWIG (SEQ ID NO: 29), wherein X1 is P or R, and X2 is G or R; VH FR3 comprises the sequence YAQKFQGRATLTEDTSTSTAYMELSSLRSEDTAVYYCAR (SEQ ID NO: 30); and VH FR4 comprises the sequence WGQGTLVTVSS (SEQ ID NO: 31); and / or the light chain comprises one, two, three, or four framework regions selected from VL FR1, VL FR2, VL FR3, and VL FR4, wherein: VL FR1 comprises the sequence of DIQMTQSPSSLSASVG DRVTITC (SEQ ID NO:32); VL FR2 comprises the sequence of WYQQKPGKAPKLLIY (SEQ ID NO:33); VL FR3 comprises the sequence of GVPSRFSGSGSGTDYTLTISSLQPEDFATYYC (SEQ ID NO:34); and VL FR4 comprises the sequence of FGQGTKLEIK (SEQ ID NO:35). In some embodiments that may be combined with any of the preceding embodiments, the heavy chain variable region comprises one, two, three, or four framework regions selected from VH FR1, VH FR2, VH FR3, and VH FR4, wherein: VH FR1 comprises the sequence of SEQ ID NO: 25; VH FR2 comprises a sequence selected from the group consisting of SEQ ID NOs: 26-28; VH FR3 comprises the sequence of SEQ ID NO: 30; and VH FR4 comprises the sequence of SEQ ID NO: 31; and / or the light chain comprises one, two, three, or four framework regions selected from VLFR1, VL FR2, VL FR3, and VL FR4, wherein: VL FR1 comprises the sequence of SEQ ID NO: 32; VL FR2 comprises the sequence of SEQ ID NO: 33; VL FR3 comprises the sequence of SEQ ID NO: 34; and VLFR4 comprises the sequence of SEQ ID NO: 35.

[0024] In some embodiments that may be combined with any of the preceding embodiments, the antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 36-48; and / or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 49-60. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 41 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 52; a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55; a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 60; or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 43 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 60.

[0025] In one aspect, the present disclosure relates to an antibody that binds to a Siglec-7 protein, wherein the antibody comprises: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 41 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 52. In one aspect, the present disclosure relates to an antibody that binds to a Siglec-7 protein, wherein the antibody comprises: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55. In one aspect, the present disclosure relates to an antibody that binds to a Siglec-7 protein, wherein the antibody comprises: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 60. In one aspect, the present disclosure relates to an antibody that binds to a Siglec-7 protein, wherein the antibody comprises: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 43 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 60.

[0026] In some embodiments that may be combined with any of the preceding embodiments, the antibody is of IgG class, IgM class, or IgA class. In some embodiments, the antibody is of IgG class and has an IgG1, IgG2, IgG3, or IgG4 isotype.

[0027] In some embodiments, the Fc region comprises an amino acid substitution at position P331S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region comprises an amino acid substitution at position L234A, L235A, and P331S, wherein the numbering of the residue positions is according to EU numbering; the Fc region comprises an amino acid substitution at position N297A, wherein the numbering of the residue positions is according to EU numbering; or the Fc region comprises an amino acid substitution at position S267E and L328F, wherein the numbering of the residue positions is according to EU numbering.

[0028] In some embodiments that may be combined with any of the preceding embodiments, the Siglec-7 protein is a non-human primate Siglec-7 protein or a human protein. In some embodiments, the Siglec-7 is a wild-type protein. In some embodiments, the Siglec-7 protein is a naturally occurring variant. In some embodiments that may be combined with any of the preceding embodiments, the Siglec-7 protein is expressed on one or more cells selected from the group consisting of: human dendritic cells, human macrophages, human monocytes, human osteoclasts, human neutrophils, human natural killer (NK) cells, human T cells, human T helper cells, human cytotoxic T cells, human granulocytes, and human microglial cells.

[0029] In some embodiments that can be combined with any of the preceding embodiments, the antibody specifically binds to a human Siglec-7 protein. In some embodiments, the antibody binds to a human Siglec-7 protein and does not cross-react with a Siglec-7 ortholog or homolog from another species. In some embodiments that can be combined with any of the preceding embodiments, the antibody is an antibody fragment that binds to an epitope comprising amino acid residues on a non-human primate Siglec-7 protein or a human Siglec-7 protein. In some embodiments that can be combined with any of the preceding embodiments, the antibody is an antibody fragment that binds to one or more human proteins selected from the group consisting of: human Siglec-7, naturally occurring variants of human Siglec-7, and disease variants of human Siglec-7. In some embodiments, the antibody fragment is cross-linked with a second antibody fragment that binds to one or more human proteins selected from the group consisting of: human Siglec-7, naturally occurring variants of human Siglec-7, and disease variants of human Siglec-7. In some embodiments, the fragment is a Fab, Fab', Fab'-SH, F(ab')2, Fv, or scFv fragment.

[0030] In some embodiments that may be combined with any of the foregoing embodiments, the antibody is a humanized antibody, a bispecific antibody, a monoclonal antibody, a multivalent antibody, a conjugated antibody, or a chimeric antibody. In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is a bispecific antibody that recognizes a first antigen and a second antigen. In some embodiments, the first antigen is Siglec-7 and the second antigen is: an antigen that promotes transport across the blood-brain barrier; an antigen that promotes transport across the blood-brain barrier selected from the group consisting of: transferrin receptor (TR), insulin receptor (HIR), insulin-like growth factor receptor (IGFR), low-density lipoprotein receptor-related proteins 1 and 2 (LPR-1 and 2), diphtheria toxin receptor, CRM197, llama single domain antibody, TMEM 30(A), protein transduction domain, TAT, Syn-B, membrane-penetrating peptide, polyarginine peptide, vascular peptide and ANG1005; a pathogenic factor selected from the group consisting of pathogenic peptides or proteins and pathogenic nucleic acids, wherein the pathogenic peptide or protein is selected from the group consisting of amyloid beta, oligomeric amyloid beta, amyloid beta plaques, amyloid precursor protein or fragments thereof, Tau, IAPP, α-synuclein, TDP-43, FUS protein, C9orf72 (chromosome 9 open reading frame 72), c9RAN protein, prion protein, PrPSc, huntingtin protein, calcitonin, superoxide dismutase, ataxin, ataxin 1, ataxin 2, ataxin 3, ataxin 7, ataxin 8, ataxin 10, pathway Easy body, atrial natriuretic factor, islet amyloid polypeptide, insulin, apolipoprotein AI, serum amyloid A, superoxide dismutase (SOD), interleukin, prolactin, transthyretin, lysozyme, β2 microglobulin, gelsolin, corneal epithelial protein, cystatin, immunoglobulin light chain AL, S-IBM protein, repeat sequence associated non-ATG (RAN) translation product, dipeptide repeat sequence (DPR) peptide, glycine-alanine (GA) repeat sequence peptide, glycine-proline (GP) repeat sequence peptide, glycine-arginine (GR) repeat sequence peptide, proline-alanine (PA) repeat sequence peptide, ubiquitin and proline-arginine (PR) repeat sequence peptide, and the pathogenic nucleic acid is antisense GGCCCC (G2C4) repeat sequence-expansion RNA;A ligand and / or protein expressed on an immune cell, wherein the ligand and / or protein is selected from the group consisting of: CD33, CD40, OX40, ICOS, CD28, CD137 / 4-1BB, CD27, GITR, PD-L1, CTLA4, PD-L2, PD-1, B7-H3, B7-H4, HVEM, LIGHT, BTLA, CD38, TIGIT, VISTA, KIR, GAL9, TIM1, TIM3, TIM4, A2AR, LAG3, DR5, CD39, CD70, CD73, TREM1, TREM2, Siglec-5, Siglec-9, Siglec-11, SirpA, CD47, CSF1 receptor, and phosphatidylserine; and a protein, lipid, polysaccharide, or glycolipid expressed on one or more tumor cells.

[0031] In some embodiments that may be combined with any of the preceding embodiments, the antibody is used in combination with one or more antibodies that specifically bind to a pathogenic factor selected from the group consisting of a pathogenic peptide, a pathogenic protein, amyloid beta, oligomeric amyloid beta, amyloid beta plaques, amyloid precursor protein or fragments thereof, Tau, IAPP, alpha-synuclein, TDP-43, FUS protein, C9orf72 (chromosome 9 open reading frame 72), prion protein, PrPSc, huntingtin protein, calcitonin, superoxide dismutase, ataxia protein, white, ataxin 1, ataxin 2, ataxin 3, ataxin 7, ataxin 8, ataxin 10, Lewy bodies, atrial natriuretic factor, islet amyloid polypeptide, insulin, apolipoprotein AI, serum amyloid A, interferon, prolactin, transthyretin, lysozyme, β2-microglobulin, gelsolin, corneal epithelial protein, cysteine ​​protease inhibitor, immunoglobulin light chain AL, superoxide dismutase (SOD), S-IBM protein, repeat-associated non-ATG (RAN) translation product, dipeptide repeat (DP) R) peptides, glycine-alanine (GA) repeat peptides, glycine-proline (GP) repeat peptides, glycine-arginine (GR) repeat peptides, proline-alanine (PA) repeat peptides, ubiquitin, and proline-arginine (PR) repeat peptides, and any combination thereof; or used in combination with one or more antibodies that bind to an immunomodulatory protein selected from the group consisting of CD33, CD40, OX40, ICOS, CD28, CD137 / 4-1BB, CD27, GITR, PD-L1, CTLA4, PD-L2, PD- 1. B7-H3, B7-H4, HVEM, LIGHT, BTLA, CD38, TIGIT, VISTA, KIR, GAL9, TIM1, TIM3, TIM4, A2AR3, DR5, CD39, CD70, CD73, LAG3, TREM1, TREM2, Siglec-5, Siglec-9, Siglec-11, SirpA, CD47, CSF1 receptor, phosphatidylserine, pathogenic nucleic acids, antisense GGCCCC (G2C4) repeat sequence expansion RNA, and any combination thereof.

[0032] In some embodiments that may be combined with any of the preceding embodiments, the antibody has a dissociation constant (K) for human Siglec-7 that is at least 4 times lower than that of an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62; or at least 1 times lower than that of an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. D ), wherein the K D In some embodiments that may be combined with any of the preceding embodiments, the antibody has a dissociation constant (K) for human Siglec-7 in the range of about 124 nM to about 1 pM or less than about 1 pM. D ), and wherein said K D It is determined by biolayer interferometry.

[0033] In some embodiments that may be combined with any of the preceding embodiments, the antibody reduces the cell surface level of Siglec-7. In some embodiments, the Siglec-7 is expressed on the surface of human dendritic cells. In some embodiments, the antibody reduces the cell surface level of Siglec-7 in vitro. In some embodiments, the antibody reduces the cell surface level of Siglec-7 in vitro at a half-maximal effective concentration (EC) of less than 150 pM as measured by flow cytometry. 50 ) reduces the cell surface level of Siglec-7. In some embodiments, the antibody has an EC of at least 50% lower in vitro than an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62; or at least 10% lower than an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50, as measured by flow cytometry. 50Reduce the cell surface level of Siglec-7. In some embodiments, the cell surface level of Siglec-7 is reduced to at least 20%. In some embodiments, the antibody is at least 4.2 times more potent than an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62, as measured by flow cytometry; or at least 1.4 times more potent than an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50.

[0034] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure compete for binding to Siglec-7 with an antibody comprising a heavy chain variable domain and a light chain variable domain of an antibody selected from the group consisting of S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8 .5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25 , S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.3 5. S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8. 45. S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB -H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.2 and any combination thereof.

[0035] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to substantially the same Siglec-7 epitope as an antibody comprising a heavy chain variable domain and a light chain variable domain of an antibody selected from the group consisting of S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H13, S7AB-H14, S7AB-H15, S7AB-H16, S7AB-H17, S7AB-H18 7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB -H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7A B-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S 7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8. 30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 and S7AB-H8.45.2.

[0036] In another aspect, the disclosure relates to an isolated nucleic acid comprising a nucleic acid sequence encoding any of the antibodies described herein.

[0037] In another aspect, the disclosure relates to a vector comprising any of the nucleic acids described herein. In some embodiments, the vector is an expression vector and / or a display vector.

[0038] In another aspect, the disclosure relates to an isolated host cell comprising any of the nucleic acids or vectors described herein.

[0039] In another aspect, the present disclosure relates to a method for producing an antibody that binds to Siglec-7, the method comprising culturing any host cell described herein to produce the antibody. In some embodiments, the method further comprises recovering the antibody produced by the cell.

[0040] In another aspect, the disclosure relates to an antibody produced by any of the methods described herein.

[0041] In another aspect, the present disclosure relates to a pharmaceutical composition comprising any of the antibodies described herein and a pharmaceutically acceptable carrier. In some embodiments, the present disclosure relates to the use of any of the antibodies described herein for the preparation of a medicament.

[0042] In another aspect, the present disclosure relates to a method for preventing a disease, disorder or injury, reducing the risk of a disease, disorder or injury, or treating a disease, disorder or injury, wherein the disease, disorder or injury is selected from the group consisting of: dementia, frontotemporal dementia, Alzheimer's disease, vascular dementia, mixed dementia, Tau protein disease, infection and cancer, the method comprising administering a therapeutically effective amount of any antibody described herein to an individual in need thereof. In some embodiments, the disease, disorder or injury is cancer. In some embodiments, the cancer is selected from the group consisting of: bladder cancer, brain cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, renal cell carcinoma, renal pelvis cancer, leukemia, lung cancer, melanoma, non-Hodgkin's lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, fibrosarcoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML) and multiple myeloma. In some embodiments, the present disclosure relates to the use of any of the antibodies described herein for the preparation of a medicament for preventing, reducing the risk of, or treating a disease, disorder, or injury selected from the group consisting of: dementia, frontotemporal dementia, Alzheimer's disease, vascular dementia, mixed dementia, Tauopathy, infection, and cancer. In some embodiments, the disease, disorder, or injury is cancer. In some embodiments, the cancer is selected from the group consisting of: bladder cancer, brain cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, renal cell carcinoma, renal pelvis cancer, leukemia, lung cancer, melanoma, non-Hodgkin's lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, fibrosarcoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and multiple myeloma. In some embodiments, the cancer expresses increased or high levels of Siglec-7 ligands. In some embodiments, the Siglec-7 ligand is one or more of α-2,3-linked sialic acid and α-2,6-linked sialic acid, disialylgalactosylerythroside, disialyllactotetraosylceramide, and / or disialylGalNAclactotetraosylceramide. In some embodiments, the cancer has increased or high levels of tumor-infiltrating NK cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 Depicted are results from a flow cytometric assay measuring binding of humanized Siglec-7 antibodies to primary human monocyte-derived dendritic cells.

[0044] Figure 2Depicts flow cytometry results measuring binding of affinity-matured humanized Siglec-7 antibodies to primary human monocyte-derived dendritic cells.

[0045] Figure 3 Depicted are results from a flow cytometric assay measuring Siglec-7 levels on the surface of primary human dendritic cells after treatment with an affinity-matured Siglec-7 antibody.

[0046] Figure 4 Depicted are results from a flow cytometric assay measuring Siglec-7 levels on the surface of primary human dendritic cells after treatment with varying concentrations of Siglec-7 antibodies containing different Fc regions.

[0047] Figure 5A Depicts flow cytometry results measuring human Siglec-7 levels on the surface of bone marrow cells in human Siglec-7 transgenic mice injected with Siglec-7 antibodies. Figure 5B Depicts flow cytometry results measuring human Siglec-7 levels on the surface of natural killer (NK) cells in human Siglec-7 transgenic mice injected with Siglec-7 antibodies.

[0048] Figure 6 Depicts measurement of circulating CD11b in human Siglec-7 transgenic mice injected with Siglec-7 antibodies + Gr1 + Flow cytometry results of human Siglec-7 levels on the cell surface.

[0049] Figure 7 Depicted are results from an assay measuring ADCC activity of Siglec-7 antibodies.

[0050] Figure 8 Depicted are results from a CDC assay in the presence of Siglec-7 antibodies. DETAILED DESCRIPTION

[0051] General techniques

[0052] The techniques and procedures described or referenced herein are generally well known to those skilled in the art and are routinely employed using conventional methodology, such as, for example, the widely used methods described in Sambrook et al., Molecular Cloning: A Laboratory Manual 3rd ed. (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Current Protocols in Molecular Biology (FM Ausubel, et al., eds., (2003)); the series Methods in Enzymology (Academic Press, Inc.): PCR 2: A Practical Approach (MJ MacPherson, BD Hames and GR Taylor, eds. (1995)), Harlow and Lane, eds. (1988) Antibodies, A Laboratory Manual, and Animal Cell Culture (RI Freshney, ed. (1987)); Oligonucleotide Synthesis (MJ Gait, ed., 1984); Methods in Molecular Biology, Humana Press; Cell Biology: A Laboratory Manual. Notebook (JECellis, editor, 1998) Academic Press; Animal Cell Culture (RI Freshney), editor, 1987); Introduction to Cell and Tissue Culture (JPMather and PERoberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Procedures (A.Doyle, JBGriffiths, and DG Newell, editor, 1993-8) J.Wiley and Sons; Handbook of Experimental Immunology (DMWeir and CC Blackwell, eds.); Gene Transfer Vectors for Mammalian Cells (JMMiller and MPCalos, eds., 1987); PCR: The Polymerase Chain Reaction, (Mullis et al., eds., 1994); Current Protocols in Immunology (JEColigan et al., eds., 1991); Short Protocols in Molecular Biology (Wiley and Sons, 1999); Immunobiology (CA Janeway and P. Travers, 1997); Antibodies (P. Finch, 1997); Antibodies: A Practical Approach (D. Catty., ed., IRL Press, 1988-1989); Monoclonal Antibodies: A Practical Approach (P. Shepherd and C. Dean, eds., Oxford University Press, 2000); Using Antibodies: A Laboratory Manual (E. Harlow and D. Lane (Cold Spring Harbor Laboratory Press, 1999); The Antibodies (M. Zanetti and JD Capra, eds., Harwood Academic Publishers, 1995); and Cancer: Principles and Practice of Oncology (VT DeVita et al., eds., JB Lippincott Company, 1993).

[0053] definition

[0054] As used herein, the term "preventing" includes providing for prevention of the occurrence or recurrence of a particular disease, disorder, or condition in an individual. An individual may be susceptible to, susceptible to, or at risk of developing a particular disease, disorder, or condition but has not yet been diagnosed with the disease, disorder, or condition.

[0055] As used herein, an individual who is "at risk" of developing a particular disease, condition, or disorder may or may not have had detectable disease or disease symptoms prior to the treatment methods described herein, and may or may not have displayed detectable disease or disease symptoms. "At risk" means that the individual has one or more risk factors, which are measurable parameters associated with the development of a particular disease, condition, or disorder as known in the art. An individual who has one or more of these risk factors has a higher likelihood of developing a particular disease, condition, or disorder than an individual who does not have one or more of these risk factors.

[0056] As used herein, the term "treatment" refers to a clinical intervention designed to alter the natural course of the treated individual during the course of clinical pathology. Desirable effects of treatment include reducing the rate of progression of a particular disease, condition, or disorder, ameliorating or alleviating the pathological state of a particular disease, condition, or disorder, and mitigating or improving the prognosis of a particular disease, condition, or disorder. For example, a subject is successfully "treated" when one or more symptoms associated with a particular disease, condition, or disorder are alleviated or eliminated.

[0057] "Effective amount" refers to an amount that, at the required dosage and for the required period, effectively achieves at least the desired therapeutic or preventive result. The effective amount can be provided in one or more administrations. The effective amount herein can vary according to a variety of factors, such as the individual's disease state, age, sex, and weight, and the ability of the treatment to elicit the desired response in the individual. An effective amount is also an amount in which the beneficial effects of the treatment outweigh any toxic or deleterious effects of the treatment. For preventive use, beneficial or desired results include results such as: eliminating or reducing risk, alleviating severity, or delaying the onset of a disease (including biochemical, histological, and / or behavioral symptoms of the disease, complications of the disease present during the disease progression, and intermediate pathological phenotypes). For therapeutic use, beneficial or desired results include clinical results such as: reducing one or more symptoms caused by the disease, improving the quality of life of patients with the disease, reducing the dosage of other drugs required to treat the disease, such as by enhancing the effect of another drug through targeting, delaying disease progression, and / or prolonging survival. The effective amount of a drug, compound, or pharmaceutical composition is an amount sufficient to directly or indirectly complete a preventive or therapeutic treatment. It is understood in a clinical context that an effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in combination with another drug, compound, or pharmaceutical composition. Thus, an "effective amount" can be considered in the context of administering one or more therapeutic agents, and a single agent can be considered to be administered in an effective amount if the desired result can be achieved or is achieved in combination with one or more other agents.

[0058] As used herein, administration "in conjunction" with another compound or composition includes simultaneous administration and / or administration at different times. Administration in conjunction also includes administration as a co-formulation or administration as separate compositions, including at different dosing frequencies or intervals and using the same route of administration or different routes of administration.

[0059] A "subject" for the purposes of treatment, prevention, or risk reduction refers to any animal classified as a mammal, including humans, domestic and farm animals, as well as zoo, sport, or pet animals, such as dogs, horses, rabbits, cows, pigs, hamsters, gerbils, mice, ferrets, rats, cats, etc. Preferably, the subject is a human.

[0060] The term "immunoglobulin" (Ig) is used interchangeably herein with "antibody." The term "antibody" herein is used in a broad sense and specifically encompasses monoclonal antibodies, polyclonal antibodies, multispecific antibodies formed from at least two intact antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired biological activity.

[0061] The basic 4-chain antibody unit is a heterotetrameric glycoprotein composed primarily of two identical light (L) chains and two identical heavy (H) chains. H and V L For the structure and properties of different classes of antibodies, see, e.g., Basic and Clinical Immunology, 8th edition, Daniel P. Stites, Abba I. Terr and Tristram G. Parslow (eds.), Appleton & Lange, Norwalk, CT, 1994, page 71 and chapter 6.

[0062] The L chains from any vertebrate species can be assigned to one of two clearly distinct types, called kappa ("κ") and lambda ("λ"), based on the amino acid sequence of their constant domains. Immunoglobulins can be assigned to different classes, or isotypes, depending on the amino acid sequence of the constant domain (CH) of their heavy chains. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, which have heavy chains designated alpha ("α"), delta ("δ"), epsilon ("ε"), gamma ("γ"), and muon ("μ"), respectively. Based on relatively small differences in CH sequence and function, the gamma and alpha classes are further divided into subclasses (isotypes); for example, humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known and generally described in, for example, Abbas et al., Cellular and Molecular Immunology, 4th ed. (WB Saunders Co., 2000).

[0063] "Native antibodies" are usually heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each light chain is linked to a heavy chain by a covalent disulfide bond, but the number of disulfide linkages varies among the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has a variable domain (V) at one end. H ), followed by multiple constant domains. Each light chain has a variable domain (V L ) and has a constant domain at the other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the variable domain of the light chain is aligned with the variable domain of the heavy chain. It is known that specific amino acid residues form the interface between the light chain variable domain and the heavy chain variable domain.

[0064] An "isolated" antibody (such as an anti-Siglec-7 antibody of the present disclosure) is an antibody that has been identified, separated and / or recovered from a component of its production environment (e.g., naturally or recombinantly). Preferably, the isolated polypeptide is free from association with all other contaminant components from its production environment. Contaminant components from its production environment (such as those produced by recombinantly transfected cells) are substances that would typically interfere with the research, diagnostic or therapeutic use of the antibody and may include enzymes, hormones, and other protein or non-protein solutes. In preferred embodiments, the polypeptide will: (1) be purified to greater than 95% by weight of the antibody as determined by, for example, the Lowry method and in some embodiments to greater than 99% by weight; (2) be purified to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence using a spinning cup sequenator; or (3) be purified to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain. Isolated antibody includes the antibody in situ within recombinant T cells since at least one component of the antibody's natural environment will not be present.Ordinarily, however, isolated polypeptide or antibody will be prepared by at least one purification step.

[0065] The "variable region" or "variable domain" of an antibody (such as the anti-Siglec-7 antibody of the present disclosure) refers to the amino terminal domain of the heavy chain or light chain of the antibody. The variable domains of the heavy chain and light chain can be referred to as "V H ” and “V L These domains are usually the most variable parts of an antibody (relative to other antibodies of the same class) and contain the antigen-binding site.

[0066] The term "variable" refers to the fact that certain segments of the variable domain differ widely in sequence between antibodies (such as the anti-Siglec-7 antibodies of the present disclosure). The V domain mediates antigen binding and defines the specificity of a particular antibody for its specific antigen. However, variability is not evenly distributed throughout the variable domain. Instead, in the light and heavy chain variable domains, variability is concentrated in three segments called hypervariable regions (HVRs). The more highly conserved parts of the variable domain are called framework regions (FRs). The variable domains of native heavy and light chains each contain four FR regions connected by three HVRs, and the four FRs essentially adopt a β-sheet configuration. The three HVRs form loops connecting the β-sheet structure and in some cases form part of the β-sheet structure. The HVRs in each chain are held close together by the FR region and contribute to the formation of the antigen-binding site of the antibody with the HVRs from the other chain (see Kabat et al., Sequences of Immunological Interest, 5th edition, National Institute of Health, Bethesda, MD (1991)). Although the constant domains are not directly involved in binding an antibody to an antigen, they exhibit various effector functions, such as participation of the antibody in antibody-dependent cellular toxicity.

[0067] As used herein, the term "monoclonal antibody" refers to an antibody (such as the anti-Siglec-7 antibody of the present disclosure) obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies constituting the population are identical, except for possible naturally occurring mutations and / or post-translational modifications (e.g., isomerization, amidation) that may be present in trace amounts. Monoclonal antibodies are highly specific, thereby being directed against one or more antigenic sites. In some embodiments, the monoclonal antibodies of the present disclosure may be bispecific antibodies. Unlike polyclonal antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on one or more antigenic sites. The modifier "monoclonal" indicates that the antibody is a property obtained from a substantially homogeneous antibody population and should not be interpreted as requiring the antibody to be produced by any particular method. For example, monoclonal antibodies to be used in accordance with the present disclosure can be prepared by various techniques, including, for example, phage display technology (see, e.g., Clackson et al., Nature, 352:624-628 (1991); Marks et al., J. Mol. Biol. 222:581-597 (1992); Sidhu et al., J. Mol. Biol. 338(2):299-310 (2004); Lee et al., J. Mol. Biol. 340(5):1073-1093 (2004); Fellouse, Proc. Nat'l Acad. Sci. USA 101(34):12467-472 (2004); and Lee et al., J. Immunol. Methods 284(1-2):119-132 (2004), the hybridoma method (e.g., Kohler and Milstein., Nature, 256:495-97 (1975); Hongo et al., Hybridoma, 14(3):253-260 (1995); Harlow et al., Antibodies: A Laboratory Manual, (Cold Spring Harbor Laboratory Press, 2nd ed. 1988); Hammerling et al., Monoclonal Antibodies and T-Cell Hybridomas 563-681 (Elsevier, NY, 1981)), recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567), and techniques for producing human or human-like antibodies in animals that have part or all of the human immunoglobulin loci or genes encoding human immunoglobulin sequences (see, e.g., WO 1998 / 24893; WO 1996 / 34096; WO 1997 / 11064). 1996 / 33735; WO 1991 / 10741; Jakobovits et al., Proc.Nat'l Acad. Sci. USA 90:2551 (1993); Jakobovits et al., Nature 362:255-258 (1993); Bruggemann et al., Year in Immunol. 7:33 (1993); U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; and 5,661,016; Marks et al., Bio / Technology 10:779-783 (1992); Lonberg et al., Nature 368:856-859 (1994); Morrison, Nature 368:812-813 (1994); Fishwild et al., Nature Biotechnol. 14:845-851 (1996); Neuberger, Nature Biotechnol. 14:826 (1996); and Lonberg and Huszar, Intern. Rev. Immunol. 13:65-93 (1995).

[0068] The terms "full-length antibody," "intact antibody," or "whole antibody" are used interchangeably to refer to an antibody in its substantially intact form, as opposed to an antibody fragment, such as the anti-Siglec-7 antibodies of the present disclosure. Specifically, whole antibodies include antibodies having heavy and light chains (including an Fc region). The constant domain may be a native sequence constant domain (e.g., a human native sequence constant domain) or an amino acid sequence variant thereof. In some cases, an intact antibody may have one or more effector functions.

[0069] "Antibody fragments" comprise a portion of an intact antibody, preferably the antigen-binding and / or variable regions of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies (see U.S. Patent 5,641,870, Example 2; Zapata et al., Protein Eng. 8(10):1057-1062 (1995)); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.

[0070] Papain digestion of antibodies (such as the anti-Siglec-7 antibodies of the present disclosure) produces two identical antigen-binding fragments called "Fab" fragments and a residual "Fc" fragment, a name that reflects the ability to crystallize readily. The Fab fragment consists of the entire L chain together with the variable region domain (V) of the H chain. H ) and the first constant domain of a heavy chain (C H1) Composition. Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of an antibody produces a single large F(ab')2 fragment that roughly corresponds to two disulfide-linked Fab fragments with different antigen-binding activities and still capable of cross-linking antigen. Fab' fragments differ from Fab fragments in that the C H The constant domains have additional residues at their carboxyl terminus, including one or more cysteines from the antibody hinge region. Fab'-SH is the designation herein for Fab' in which one or more cysteine ​​residues of the constant domains bear a free thiol group. F(ab')2 antibody fragments originally were produced as pairs of Fab' fragments with hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

[0071] The Fc fragment comprises the carboxyl-terminal portions of two H chains held together by disulfides.The effector functions of an antibody are determined by sequences in the Fc region, which is also recognized by Fc receptors (FcR) found on certain types of cells.

[0072] "Fv" is the smallest antibody fragment containing a complete antigen recognition and binding site. This fragment consists of a dimer of a heavy chain variable region domain and a light chain variable region domain in tight, non-covalent association. From the folding of these two domains, six hypervariable loops (3 loops each from the H and L chains) are emitted, which contribute amino acid residues for antigen binding and give the antibody antigen-binding specificity. However, even a single variable domain (or half an Fv comprising only three HVRs specific for an antigen) has the ability to recognize and bind to an antigen, although at a lower affinity than the entire binding site.

[0073] "Single-chain Fv", also abbreviated as "sFv" or "scFv", is an antibody fragment comprising the VH and VL antibody domains linked into a single polypeptide chain. Preferably, the sFv polypeptide also comprises a V H With V L A polypeptide linker between the domains that enables the sFv to form the structure required for antigen binding. For a review of sFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, Vol. 113, Rosenburg and Moore, eds., Springer-Verlag, New York, pp. 269-315 (1994).

[0074] A "functional fragment" of an antibody (such as an anti-Siglec-7 antibody of the present disclosure) comprises a portion of an intact antibody, generally including the antigen-binding region or variable region of the intact antibody or the F region of the antibody, wherein the F region retains or has altered FcR binding ability. Examples of antibody fragments include linear antibodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments.

[0075] The term "diabody" refers to a H With V L Small antibody fragments prepared by constructing sFv fragments (see previous paragraph) with short linkers (about 5-10 residues) between the domains to enable interchain rather than intrachain pairing of the V domains, thereby generating bivalent fragments, i.e., fragments with two antigen-binding sites. Bispecific diabodies are heterodimers of two "crossover" sFv fragments, in which the V domains of the two antibodies are H and V L The domains are present on different polypeptide chains. Diabodies are described in more detail in, for example, EP 404,097; WO 93 / 11161; Hollinger et al., Proc. Nat'l Acad. Sci. USA 90:6444-48 (1993).

[0076] As used herein, "chimeric antibody" refers to an antibody (immunoglobulin), such as the chimeric anti-Siglec-7 antibody of the present disclosure, in which a portion of the heavy chain and / or light chain is identical or homologous to the corresponding sequence in an antibody derived from a particular species or belonging to a particular antibody class or subclass, and the remainder of the chain is identical or homologous to the corresponding sequence in an antibody derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, as long as they exhibit the desired biological activity (U.S. Patent No. 4,816,567; Morrison et al., Proc. Nat'l Acad. Sci. USA, 81: 6851-55 (1984)). The chimeric antibodies of interest herein include An antibody, wherein the antigen binding region of the antibody is derived from an antibody produced by, for example, immunizing a macaque with the antigen of interest. As used herein, "humanized antibody" is used for a subset of "chimeric antibodies."

[0077] "Humanized" forms of non-human (e.g., murine) antibodies (such as the anti-Siglec-7 antibodies of the present disclosure) are chimeric antibodies containing minimal sequences derived from non-human immunoglobulins. In one embodiment, a humanized antibody is a human immunoglobulin (recipient antibody) in which residues from the recipient's HVR are replaced with residues having the desired specificity, affinity, and capacity from a non-human species (donor antibody) such as a mouse, rat, rabbit, or non-human primate. In some cases, the FR residues of the human immunoglobulin are replaced with corresponding non-human residues. In addition, humanized antibodies may contain residues that are not found in the recipient antibody or in the donor antibody. These modifications can be made to further refine antibody performance, such as binding affinity. Typically, a humanized antibody will comprise substantially all of at least one and usually two variable domains, wherein all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin sequence and all or substantially all of the FR regions are those of a human immunoglobulin sequence, but the FR regions may comprise one or more individual FR residue substitutions that improve antibody performance, such as binding affinity, isomerization, immunogenicity, and the like. The number of these amino acid substitutions in the FR is typically no more than 6 in the H chain and no more than 3 in the L chain. The humanized antibody may optionally also include at least a portion of an immunoglobulin constant region (Fc), typically a portion of a human immunoglobulin. For further details, see, for example, Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992). See also, eg, Vaswani and Hamilton, Ann. Allergy, Asthma & Immunol. 1: 105-115 (1998); Harris, Biochem. Soc. Transactions 23: 1035-1038 (1995); Hurle and Gross, Curr. Op. Biotech. 5: 428-433 (1994); and US Pat. Nos. 6,982,321 and 7,087,409.

[0078] A "human antibody" is an antibody having an amino acid sequence corresponding to the amino acid sequence of an antibody produced by a human (such as the anti-Siglec-7 antibody of the present disclosure) and / or has been made using any of the techniques for preparing human antibodies as disclosed herein. The definition of a human antibody specifically excludes humanized antibodies that include non-human antigen-binding residues. Human antibodies can be produced using various techniques known in the art, including phage display libraries. Hoogenboom and Winter, J. Mol. Biol., 227: 381 (1991); Marks et al., J. Mol. Biol., 222: 581 (1991). Methods that can also be used to prepare human monoclonal antibodies are those described in Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boerner et al., J. Immunol., 147 (1): 86-95 (1991). See also van Dijk and van de Winkel, Curr. Opin. Pharmacol. 5:368-74 (2001). Human antibodies can be prepared by administering an antigen to a transgenic animal that has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled, such as an immunized xenogeneic mouse (for XENOMOUSE TM For human antibodies generated via human B cell hybridoma technology, see, eg, US Pat. Nos. 6,075,181 and 6,150,584. For human antibodies generated via human B cell hybridoma technology, see also, eg, Li et al., Proc. Nat'l Acad. Sci. USA, 103:3557-3562 (2006).

[0079] As used herein, the term "hypervariable region," "HVR," or "HV" refers to regions of an antibody variable domain, such as the regions of the anti-Siglec-7 antibodies of the present disclosure, that are hypervariable in sequence and / or form structurally defined loops. In general, antibodies contain six HVRs; three in VH (H1, H2, H3) and three in VL (L1, L2, L3). In natural antibodies, H3 and L3 display the most diversity of the six HVRs, and H3 in particular is believed to play a unique role in conferring good specificity to antibodies. See, for example, Xu et al., Immunity 13:37-45 (2000); Johnson and Wu in Methods in Molecular Biology 248:1-25 (Lo, ed., Human Press, Totowa, NJ, 2003). In fact, naturally occurring camelid antibodies composed of heavy chains are functional and stable only in the absence of light chains. See, eg, Hamers-Casterman et al., Nature 363:446-448 (1993) and Sheriff et al., Nature Struct. Biol. 3:733-736 (1996).

[0080] Many HVR descriptions are in use, and are included in this article. In some embodiments, the HVR can be the Kabat complementary determining region (CDR) based on sequence variability and is the most commonly used (Kabat et al., supra). In some embodiments, the HVR can be a Clothia CDR. And Chothia refers to the position of the structural loop (Chothia and Lesk J. Mol. Biol. 196: 901-917 (1987)). In some embodiments, the HVR can be an AbM CDR. AbM HVR represents a compromise between Kabat CDR and Chothia structural loop, and is used by the AbM antibody modeling software of Oxford Molecular. In some embodiments, the HVR can be a "contact" CDR. "Contact" HVR is based on analyzing available complex crystal structure. The residues from each of these HVRs are described below.

[0081]

[0082] An HVR may comprise an "extended HVR" as follows: 24-36 or 24-34 (L1), 46-56 or 50-56 (L2), and 89-97 or 89-96 (L3) in VL, and 26-35 (H1), 50-65 or 49-65 (preferred embodiments) (H2), and 93-102, 94-102, or 95-102 (H3) in VH. For each of these extended HVR definitions, the variable domain residues are numbered according to EU or Kabat et al., supra.

[0083] "Framework" or "FR" residues are those variable domain residues other than the HVR residues as herein defined.

[0084] The phrase "variable domain residue numbering as in Kabat" or "amino acid position numbering as in Kabat" and variations thereof refer to the numbering system used for the heavy chain variable domain or light chain variable domain of the antibody compilations in Kabat et al., supra. Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a FR or HVR of the variable domain. For example, the heavy chain variable domain may include a single amino acid insertion after residue 52 of H2 (residue 52a according to Kabat) and inserted residues after heavy chain FR residue 82 (e.g., residues 82a, 82b, and 82c, etc. according to Kabat). The Kabat numbering of residues for a given antibody can be determined by alignment with the "standard" Kabat numbering sequence at homologous regions of the antibody sequence.

[0085] When referring to residues in the variable domain, the Kabat numbering system is generally used (approximately residues 1-107 of the light chain and residues 1-113 of the heavy chain) (e.g., Kabat et al., Sequences of Immunological Interest. 5th ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991)). The "EU numbering system" or "EU index" is generally used when referring to residues in the constant region of an immunoglobulin heavy chain (e.g., Kabat et al., EU index reported above). The "EU index as in Kabat" refers to the residue numbering of human IgG1 EU antibodies. Unless otherwise indicated herein, references to residue numbering in the variable domain of an antibody refer to residues numbered by the Kabat numbering system. Unless otherwise indicated herein, references to residue numbering in the constant domain of an antibody refer to residues numbered by the EU numbering system (e.g., see U.S. Patent Publication No. 2010-280227).

[0086] As used herein, an "acceptor human framework" is a framework comprising the amino acid sequence of a VL or VH framework derived from a human immunoglobulin framework or a human consensus framework. An acceptor human framework "derived from" a human immunoglobulin framework or a human consensus framework may comprise the same amino acid sequence thereof, or it may contain pre-existing amino acid sequence changes. In some embodiments, the number of pre-existing amino acid changes is 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3 or less, or 2 or less. When pre-existing amino acid changes are present in VH, it is preferred that those changes occur only at three, two, or one of positions 71H, 73H, and 78H; for example, the amino acid residues at those positions may be 71A, 73T, and / or 78A. In one embodiment, the VL acceptor human framework is identical in sequence to the VL human immunoglobulin framework sequence or the human consensus framework sequence.

[0087] A "human consensus framework" is a framework that represents the most commonly occurring amino acid residues in a selection of human immunoglobulin VL or VH framework sequences. In general, a human immunoglobulin VL or VH sequence is selected from a subset of variable domain sequences. In general, the sequence subset is a subgroup as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991). Examples include for VL, the subgroup may be subgroup κI, κII, κIII, or κIV as described in Kabat et al., supra. In addition, for VH, the subgroup may be subgroup I, subgroup II, or subgroup III as described in Kabat et al., supra.

[0088] For example, an "amino acid modification" at a specified position of an anti-Siglec-7 antibody disclosed herein refers to a substitution or deletion of the specified residue, or an insertion of at least one amino acid residue adjacent to the specified residue. An insertion "adjacent" to a specified residue refers to an insertion within one to two residues thereof. The insertion may be at the N-terminus or C-terminus of the specified residue. The preferred amino acid modification herein is a substitution.

[0089] "Affinity matured" antibodies (such as the anti-Siglec-7 antibodies of the present disclosure) are antibodies with one or more changes in one or more HVRs that result in an increase in the affinity of the antibody for the antigen compared to a parent antibody that does not have those changes. In one embodiment, the affinity matured antibody has nanomolar or even picomolar affinities for the target antigen. Affinity matured antibodies are produced by procedures known in the art. For example, Marks et al., Bio / Technology 10:779-783 (1992) describe affinity maturation by VH- and VL-domain shuffling. Random mutagenesis of HVR and / or framework residues is described, for example, by Barbas et al. Proc Nat. Acad. Sci. USA 91:3809-3813 (1994); Schier et al. Gene 169:147-155 (1995); Yelton et al. J. Immunol. 155:1994-2004 (1995); Jackson et al. J. Immunol. 154(7):3310-9 (1995); and Hawkins et al. J. Mol. Biol. 226:889-896 (1992).

[0090] As used herein, the term "specifically recognizes" or "specifically binds" refers to a measurable and reproducible interaction, such as an attraction or binding between a target and an antibody (such as an anti-Siglec-7 antibody of the present disclosure), which determines the presence of the target in the presence of a heterogeneous population of molecules including biological molecules. For example, an antibody (such as an anti-Siglec-7 antibody of the present disclosure) that specifically or preferentially binds to a target or epitope binds to the target or epitope with greater affinity, avidity, greater ease, and / or greater duration than it binds to other targets or other epitopes of the target. It should also be understood by reading this definition that, for example, an antibody (or portion) that specifically or preferentially binds to a first target may or may not specifically or preferentially bind to a second target. Thus, "specific binding" or "preferential binding" does not necessarily require (although it may include) exclusive binding. An antibody that specifically binds to a target may have a specific binding affinity of at least about 10 3 M -1 or 10 4 M -1 , sometimes about 10 5 M -1 or 10 6 M -1 , in other cases about 10 6 M -1 or 10 7 M -1 , about 10 8 M -1 to 109 M -1 or about 10 10 M -1 to 10 11 M -1 or higher association constant. A variety of immunoassay formats can be used to select antibodies that are specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select monoclonal antibodies that are specifically immunoreactive with a protein. For a description of immunoassay formats and conditions that can be used to determine specific immunoreactions, see, for example, Harlow and Lane (1988) Antibodies, A Laboratory Manual, Cold Spring Harbor Publications, New York.

[0091] As used herein, "interaction" between a Siglec-7 protein and a second protein includes, but is not limited to, protein-protein interactions, physical interactions, chemical interactions, binding, covalent binding, and ionic binding. As used herein, an antibody "inhibits an interaction between two proteins" when it disrupts, reduces, or completely eliminates the interaction between the two proteins. An antibody or fragment thereof of the present disclosure "inhibits an interaction between two proteins" when it binds to one of the two proteins.

[0092] An “agonist” antibody or “activating” antibody is an antibody that induces (e.g., increases) one or more activities or functions of an antigen after the antibody binds to the antigen, such as the agonist anti-Siglec-7 antibodies of the present disclosure.

[0093] "Blocking" antibodies, "antagonist" antibodies, or "inhibitory" antibodies are antibodies that inhibit or reduce (e.g., decrease) the binding of the antibody to one or more ligands after the antibody binds to the antigen and / or inhibit or reduce (e.g., decrease) one or more activities or functions of the antigen after the antibody binds to the antigen, such as the anti-Siglec-7 antibodies of the present disclosure. In some embodiments, the blocking antibody, antagonist antibody, or inhibitory antibody substantially or completely inhibits the binding of the antigen to one or more ligands of the antigen and / or one or more activities or functions of the antigen.

[0094] Antibody "effector functions" refer to those biological activities attributable to the Fc region (a native sequence Fc region or amino acid sequence variant Fc region) of an antibody, and vary with the antibody isotype.

[0095] The term "Fc region" herein is used to define the C-terminal region of an immunoglobulin heavy chain, including native sequence Fc regions and variant Fc regions. Although the boundaries of the Fc region of an immunoglobulin heavy chain may 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. For example, the C-terminal lysine (residue 447 according to EU or Kabat numbering system) in the Fc region can be, for example, during the production or purification of an antibody or by recombinant engineering of a nucleic acid encoding an antibody heavy chain. Therefore, the composition of a complete antibody can include an antibody population that removes all K447 residues, an antibody population that does not remove the K447 residue, and an antibody population with an antibody mixture having or without the K447 residue. Suitable native sequence Fc regions for antibodies of the present disclosure include human IgG1, IgG2, IgG3, and IgG4.

[0096] A "native sequence Fc region" comprises an amino acid sequence identical to the amino acid sequence of an Fc region found in nature. Native sequence human Fc regions include native sequence human IgG1 Fc regions (non-A and A allotypes); native sequence human IgG2 Fc regions; native sequence human IgG3 Fc regions; and native sequence human IgG4 Fc regions, as well as naturally occurring variants thereof.

[0097] A "variant Fc region" comprises an amino acid sequence that differs from the amino acid sequence of a native sequence Fc region by at least one amino acid modification, preferably one or more amino acid sequences. Preferably, the variant Fc region has at least one amino acid substitution compared to the native sequence Fc region or the Fc region of a parent polypeptide, for example, from about 1 to about 10 amino acid substitutions in the native sequence Fc region or in the Fc region of the parent polypeptide, and preferably from about 1 to about 5 amino acid substitutions. The variant Fc region herein will preferably have at least about 80% homology to the native sequence Fc region and / or to the Fc region of the parent polypeptide, and most preferably at least about 90% homology thereto, and more preferably at least about 95% homology thereto.

[0098] "Fc receptor" or "FcR" describes a receptor that binds to the Fc region of an antibody. A preferred FcR is a native sequence human FcR. In addition, a preferred FcR is one that binds to IgG antibodies (gamma receptors) and includes receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced ​​forms of these receptors, FcγRII receptors including FcγRIIA ("activating receptor") and FcγRIIB ("inhibiting receptor"), which have similar amino acid sequences that differ primarily in their cytoplasmic domains. The activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif ("ITAM") in its cytoplasmic domain. The inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif ("ITIM") in its cytoplasmic domain. (See, e.g., M. FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol. 9:457-92 (1991); Capel et al., Immunomethods 4:25-34 (1994); and deHaas et al., J. Lab. Clin. Med. 126:330-41 (1995). The term "FcR" herein encompasses other FcRs, including those to be identified in the future. FcRs may also increase the serum half-life of antibodies.

[0099] Binding to FcRn in vivo and the serum half-life of high-affinity human FcRn binding polypeptides can be determined, for example, in transgenic mice or transfected human cell lines expressing human FcRn, or in primates administered polypeptides having variant Fc regions. WO 2004 / 42072 (Presta) describes antibody variants with improved or reduced binding to FcRs. See also, for example, Shields et al., J. Biol. Chem. 9(2):6591-6604 (2001).

[0100] As used herein, "percent (%) amino acid sequence identity" and "homology" with respect to peptide, polypeptide or antibody sequences refer to the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in a particular peptide or polypeptide sequence, after aligning the sequences and introducing gaps (if necessary) to achieve the maximum percentage of sequence identity, without considering any conservative substitutions as part of the sequence identity. Alignment for the purpose of determining percent amino acid sequence identity can be achieved in a variety of ways that are within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN or MEGALIGN TM(DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms known in the art needed to achieve maximal alignment over the full length of the sequences being compared.

[0101] An "isolated" cell is a molecule or cell that has been identified and separated from at least one contaminating cell with which it is normally associated in the environment in which it was produced. In some embodiments, the isolated cell is free from all components associated with the production environment. The isolated cell is in a form or configuration that is different from that in which it exists in nature. The isolated cell is different from the cells naturally occurring in a tissue, organ, or individual. In some embodiments, the isolated cell is a host cell of the present disclosure.

[0102] An "isolated" nucleic acid molecule encoding an antibody (such as an anti-Siglec-7 antibody of the present disclosure) is a nucleic acid molecule that has been identified and separated from at least one contaminating nucleic acid molecule with which it is normally associated in the environment in which it is produced. Preferably, the isolated nucleic acid is not associated with all components associated with the production environment. The isolated nucleic acid molecule encoding the polypeptides and antibodies herein is in a form or configuration that is different from that in which it exists in nature. The isolated nucleic acid molecule is therefore different from the nucleic acid encoding the polypeptides and antibodies herein that is naturally present in a cell.

[0103] As used herein, the term "vector" means a nucleic acid molecule capable of transporting another nucleic acid to which it has been connected. One type of vector is a "plasmid", which refers to a circular double-stranded DNA to which an additional DNA segment can be connected. Another type of vector is a phage vector. Another type of vector is a viral vector, in which an additional DNA segment can be connected to a viral genome. Some vectors can replicate autonomously in the host cell into which they are introduced (for example, bacterial vectors and additional mammalian vectors with bacterial replication origins). Other vectors (for example, non-additional mammalian vectors) can be integrated into the genome of the host cell after being introduced into the host cell, and thus replicated together with the host genome. In addition, some vectors can instruct the expression of the gene to which they are operably connected. The vector is referred to as a "recombinant expression vector" or simply "expression vector" in this article. Generally speaking, the expression vector that can be used in recombinant DNA technology is often in the form of a plasmid. In this manual, "plasmid" and "vector" are used interchangeably because plasmid is the most commonly used form of vector.

[0104] "Polynucleotide" or "nucleic acid," as used interchangeably herein, refers to a polymer of nucleotides of any length, and includes DNA and RNA. The nucleotides may be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase or by a synthesis reaction. A polynucleotide may contain modified nucleotides, such as methylated nucleotides and their analogs. If present, modifications to the nucleotide structure may be imparted before or after polymer assembly. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may contain modifications performed post-synthesis, such as conjugation to a label. Other types of modifications include, for example, "capping," substitution of one or more naturally occurring nucleotides with an analog, internucleotide modifications such as, for example, those with uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoamidates, carbamates, etc.) and those with charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), those containing pendant moieties such as, for example, proteins (e.g., nucleases, toxins, antibodies, signal peptides, poly-L-lysine, etc.), those with intercalators (e.g., acridine, psoralen), those containing chelators (e.g., metals, radiometals, boron, oxidized metals, etc.), those containing alkylators, those with modified linkages (e.g., alpha anomeric nucleic acids, etc.), and one or more unmodified forms of the polynucleotide. In addition, any hydroxyl group that is usually present in carbohydrate can be replaced by (for example) phosphonate group, phosphate group, protected by standard protecting group or activated to provide other linkage with other nucleotide, or can be conjugated with solid or semisolid support.5' and 3' terminal OH can be phosphorylated or replaced by amine or organic capping group part with 1 to 20 carbon atoms.Other hydroxyl groups can also be derived into standard protecting group.Polynucleotide can also comprise similar forms of ribose or deoxyribose well known in the art, including, for example, 2'-O-methyl-, 2'-O-allyl, 2'-fluoro- or 2'-azido-ribose, carbocyclic sugar analogs, α-anomer sugar, epimerized sugar (such as arabinose, xylose or lyxose), pyranose sugar, furanose sugar, sedoheptulose, acyclic analogs and alkaline nucleoside analogs (such as methyl nucleoside).One or more phosphodiester linkages can be replaced by alternative linking groups.These alternative linking groups include, but are not limited to, embodiments in which the phosphate is replaced by P(O)S ("thioate"), P(S)S ("dithioate"), (O)NR2 ("amidate"), P(O)R, P(O)OR', CO, or CH2 ("formacetal"), wherein each R or R' is independently H or a substituted or unsubstituted alkyl (1-20 C), aryl, alkenyl, cycloalkyl, cycloalkenyl, or araldyl group optionally containing an ether (-O-) linkage. Not all linkages in a polynucleotide need be identical. The foregoing description applies to all polynucleotides referred to herein, including RNA and DNA.

[0105] "Host cell" includes an individual cell or cell culture that can be or has been a recipient of a vector for incorporating a polynucleotide insert. Host cells include the progeny of a single host cell, and the progeny may not necessarily be completely identical (in morphology or in genomic DNA complement) to the original parent cell due to natural, accidental, or deliberate mutation. Host cells include cells transfected in vivo with a polynucleotide of the present disclosure.

[0106] As used herein, "carrier" includes pharmaceutically acceptable carriers, excipients, or stabilizers that are non-toxic to cells or mammals exposed thereto at the dosages and concentrations employed. Typically, a physiologically acceptable carrier is a pH-buffered aqueous solution. Examples of physiologically acceptable carriers include buffers such as phosphates, citrates, and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or nonionic surfactants such as TWEEN®. TM , polyethylene glycol (PEG) and PLURONICS TM .

[0107] As used herein, the term "about" refers to the usual error range of the corresponding value that is readily known to those skilled in the art. References herein to "about" a value or parameter include (and describe) embodiments for the value or parameter itself.

[0108] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. For example, reference to an "antibody" is a reference to one to many antibodies (e.g., molar amounts) and includes equivalents thereof known to those skilled in the art, etc.

[0109] It should be understood that aspects and embodiments of the present disclosure described herein include "comprising," "consisting of," and / or "consisting essentially of" aspects and embodiments.

[0110] Overview

[0111] The present disclosure relates in part to anti-Siglec-7 antibodies that exhibit one or more improved and / or enhanced functional characteristics relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62, or relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 38 and a light chain variable region comprising the sequence of SEQ ID NO: 50. Non-limiting improved and / or enhanced functional properties include, for example, the ability of the antibody to bind Siglec-7 with higher affinity, reduce cell surface levels of Siglec-7, reduce the half-maximal effective concentration (EC) for downregulating cell surface levels of Siglec-7, 50 ), improving the maximum reduction of Siglec-7 cell surface levels, or any combination thereof. Also contemplated herein are anti-Siglec-7 antibodies with different Fc variants that exhibit one or more improved and / or enhanced functional characteristics, including reducing the half-maximal effective concentration (EC) for downregulating Siglec-7 cell surface levels. 50 ) and improved maximal reduction of Siglec-7 cell surface levels.

[0112] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have greater potency in reducing cell surface levels of Siglec-7 relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62, or relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 38 and a light chain variable region comprising the sequence of SEQ ID NO: 50.

[0113] The present disclosure further relates to methods of making and using the anti-Siglec-7 antibodies described herein; pharmaceutical compositions containing such antibodies; nucleic acids encoding such antibodies; and host cells containing nucleic acids encoding such antibodies.

[0114] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure may have one or more activities that are at least in part due to the ability of the antibody to reduce cellular expression (e.g., cell surface expression) of Siglec-7 by inducing degradation, downregulation, cleavage, receptor desensitization, and / or lysosomal targeting of Siglec-7. In some embodiments, the anti-Siglec-7 antibodies exhibit one or more of the following properties: a. having a lower dissociation constant (K) for human Siglec-7 than an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62. D ); b. bind to human cells, such as primary human dendritic cells; c. bind to human cells at a half-maximal effective concentration (EC) of an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62. 50 ) reduce the cell surface level of Siglec-7 (e.g., reduce the cell surface level of Siglec-7 on primary human dendritic cells in vitro); d. For example, when K is measured by surface plasmon resonance or biolayer interferometry D When , it has a dissociation constant (K ) for human Siglec-7 that can range from about 0.001 nM to about 124 nM. D ); and / or e. For example, when EC is determined in vitro by flow cytometry 50 When the half-maximal effective concentration (EC) can be in the range of about 33.2 pM to about 25.4 nM, 50 ) reduces the cell surface level of Siglec-7 (e.g., reduces the cell surface level of Siglec-7 on primary human dendritic cells in vitro). As disclosed herein, the half-maximal effective concentration (EC 50 ) refers to the concentration at which the anti-Siglec-7 antibody of the present disclosure reduces the cellular level of Siglec-7 on or in a cell to half the cellular level of Siglec-7 in untreated cells, or the concentration at which the antibody achieves half-maximal binding to Siglec-7 on a cell.

[0115] Advantageously, the anti-Siglec-7 antibodies of the present disclosure are more effective (e.g., with a lower EC ) than a control anti-Siglec-7 antibody (e.g., a control anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62). 50 ) reduces cell surface expression of Siglec-7 (e.g., by about 30.8-fold) (see, e.g., Example 3). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure are more effective (e.g., with a lower EC) than a control anti-Siglec-7 antibody (e.g., a control anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 38 and a light chain variable region comprising the sequence of SEQ ID NO: 50). 50 ) reduces the cell surface expression of Siglec-7 (e.g., by about 10.2-fold) (see, e.g., Example 3). In addition, advantageously, the anti-Siglec-7 antibodies of the present disclosure have a higher affinity for Siglec-7 (e.g., up to about 1,240-fold higher affinity) (e.g., as measured by biolayer interferometry) than a control anti-Siglec-7 antibody (e.g., a control anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62) (e.g., a lower K value as measured by biolayer interferometry). D values) (see, e.g., Examples 1 and 3). Surprisingly, higher affinity for Siglec-7 does not necessarily correlate with increased ability to reduce cell surface expression of Siglec-7 or efficacy (see, e.g., Examples 2 and 5).

[0116] Siglec-7 protein

[0117] In one aspect, the present disclosure provides antibodies, such as isolated (e.g., monoclonal) antibodies, that interact with or otherwise bind to a region (e.g., an epitope) within a Siglec-7 protein of the present disclosure. In some embodiments, the antibody interacts with or otherwise binds to a region (e.g., an epitope) within a Siglec-7 protein of the present disclosure with improved / enhanced kinetics (e.g., relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising a sequence of SEQ ID NO: 61 and a light chain variable region comprising a sequence of SEQ ID NO: 62). In some embodiments, the antibody interacts with or otherwise binds to a region (e.g., an epitope) within a Siglec-7 protein of the present disclosure at a lower half-maximal effective concentration (EC) than a control antibody (e.g., relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising a sequence of SEQ ID NO: 61 and a light chain variable region comprising a sequence of SEQ ID NO: 62). 50) interacts with or otherwise binds to a region (e.g., an epitope) within a Siglec-7 protein on a human cell (e.g., a dendritic cell). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to a Siglec-7 protein and, after binding to the Siglec-7 protein, modulate one or more Siglec-7 activities, e.g., an activity associated with Siglec-7 expression on a cell. The Siglec-7 proteins of the present disclosure include, but are not limited to, mammalian Siglec-7 proteins, non-human primate Siglec-7 proteins, and human Siglec-7 proteins.

[0118] Siglec-7 is variously referred to as Siglec-7 molecule, sialic acid-binding Ig-like lectin 7, AIRM1, CD328, CDw328, D-Siglec, QA79, SIGLEC19P, SIGLECP2, p75, and p75 / AIRM1.

[0119] Siglec-7 is an immunoglobulin-like receptor expressed primarily on immune and hematopoietic cells, including but not limited to monocytes, macrophages, dendritic cells, neutrophils, mast cells, microglia, lymphocytes, natural killer cells, and T-cell subsets.

[0120] The amino acid sequence of human Siglec-7 is listed below as SEQ ID NO: 63:

[0121]

[0122] In some embodiments, the Siglec-7 is a preprotein comprising a signal sequence. In some embodiments, the Siglec-7 is a mature protein. In some embodiments, the mature Siglec-7 protein does not comprise a signal sequence. In some embodiments, the mature Siglec-7 protein is expressed on a cell. In some embodiments, the mature Siglec-7 protein is expressed on a cell, such as a cell surface, and the cells include but are not limited to human dendritic cells, human macrophages, human monocytes, human osteoclasts, human neutrophils, human NK cells, human T cells, human helper T cells, human cytotoxic T cells, human granulocytes and human microglial cells. The anti-Siglec-7 antibodies of the present disclosure can bind to any Siglec-7 protein of the present disclosure expressed on any cell disclosed herein.

[0123] The Siglec-7 proteins of the present disclosure (such as human Siglec-7) contain several domains, including but not limited to a signal sequence located at amino acid residues 1-18 of SEQ ID NO: 63, an extracellular immunoglobulin-like variable (IgV) domain located at amino acid residues 39-122 of SEQ ID NO: 63, two Ig-like C2-type domains located at amino acid residues 150-233 and 240-336 of SEQ ID NO: 63, a transmembrane domain located at amino acid residues 354-376 of SEQ ID NO: 63, an ITIM motif 1 located at amino acid residues 435-440 of SEQ ID NO: 63, and an ITIM motif 2 located at amino acid residues 459-463 of SEQ ID NO: 63. As will be appreciated by those skilled in the art, the start and end residues of the domains of the present disclosure may vary depending on the computer modeling program used or the method used to determine the domains.

[0124] Certain aspects of the present disclosure provide anti-Siglec-7 antibodies that bind to human Siglec-7 or its homologs (including but not limited to non-human primate Siglec-7 proteins and Siglec-7 orthologs from other non-human primate species). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure (e.g., relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62) bind to human Siglec-7 or its homologs with improved / enhanced binding kinetics.

[0125] Therefore, as used herein, the "Siglec-7" protein of the present disclosure includes, but is not limited to, mammalian Siglec-7 proteins, non-human primate Siglec-7 proteins, human Siglec-7 proteins, and primate Siglec-7 proteins. In addition, the anti-Siglec-7 antibodies of the present disclosure can bind to epitopes within human Siglec-7 proteins or primate Siglec-7 proteins. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure can specifically bind to human Siglec-7.

[0126] In some embodiments, the antibodies of the present disclosure can bind to Siglec-7 in a pH-dependent manner. In some embodiments, the antibodies of the present disclosure can bind to Siglec-7 at neutral pH and be internalized without dissociating from the Siglec-7 protein. Alternatively, at acidic pH, the antibodies of the present disclosure can dissociate from Siglec-7 once internalized and subsequently degraded through the endosomal / lysosomal pathway. In certain embodiments, the anti-Siglec-7 antibodies bind to Siglec-7 at a pH in the range of 5.5 to 8.0, 5.5 to 7.5, 5.5 to 7.0, 5.5 to 6.5, 5.5 to 6.0, 6.0 to 8.0, 6.5 to 8.0, 7.0 to 8.0, 7.5 to 8.0, 6.0 to 7.5, 6.0 to 7.0, 6.5 to 7.5. In certain embodiments, the anti-Siglec-7 antibody dissociates from Siglec-7 at a pH of less than 6.0, less than 5.5, less than 5.0, less than 4.5, less than 4.0, less than 3.5, less than 3.0, less than 2.5, or less than 2.0.

[0127] In some embodiments, the antibodies of the present disclosure bind to a wild-type Siglec-7 protein of the present disclosure, a naturally occurring variant thereof, and / or a disease variant thereof.

[0128] In some embodiments, the antibodies of the present disclosure that reduce the cellular level of Siglec-7 bind to Siglec-7 proteins expressed on the cell surface, and the cells include but are not limited to human dendritic cells, human macrophages, human NK cells, human monocytes, human osteoclasts, human neutrophils, human T cells, human T helper cells, human cytotoxic T cells, human granulocytes, human bone marrow-derived immunosuppressive cells and human microglial cells. In some embodiments, the antibodies of the present disclosure that reduce the cellular level of Siglec-7 and / or inhibit the interaction between Siglec-7 and one or more Siglec-7 ligands or bind to or interact with Siglec-7 bind to Siglec-7 proteins expressed on the cell surface and regulate (e.g., induce or inhibit) at least one Siglec-7 activity of the present disclosure after binding to the surface-expressed Siglec-7 protein. In some embodiments of the present disclosure, the anti-Siglec-7 antibody specifically binds to the Siglec-7 protein. In some embodiments of the present disclosure, the anti-Siglec-7 antibody further binds to at least one additional Siglec protein. In some embodiments, the anti-Siglec-7 antibody modulates one or more activities of at least one additional Siglec protein or a cell expressing the at least one additional Siglec protein.

[0129] Siglec-7 ligands

[0130] The Siglec-7 proteins of the present disclosure can interact with (e.g., bind to) one or more Siglec-7 ligands.

[0131] Exemplary Siglec-7 ligands include, but are not limited to, sialic acid, sialic acid-containing glycolipids, sialic acid-containing glycoproteins, α-2,8-disialoglycolipids, glycoproteins containing branched α-2,6-linked sialic acid, glycolipids containing terminal α-2,6-linked sialic acid, glycoproteins containing terminal α-2,3-linked sialic acid, disialogangliosides (e.g., gangliosides or glycolipids containing ceramide linked to sialylated glycans), secreted mucins, Siglec-7 ligands expressed on erythrocytes, Siglec-7 ligands expressed on bacterial cells, Siglec-7 ligands expressed on apoptotic cells, and glycoproteins containing branched α-2,6-linked sialic acid. Siglec-7 ligands expressed on neural cells, Siglec-7 ligands expressed on glial cells, Siglec-7 ligands expressed on microglial cells, Siglec-7 ligands expressed on astrocytes, Siglec-7 ligands expressed on tumor cells, Siglec-7 ligands expressed on viruses, Siglec-7 ligands expressed on dendritic cells, Siglec-7 ligands bound to β-amyloid plaques, Siglec-7 ligands bound to Tau tangles, pathogenic proteins Siglec-7 ligands on white, Siglec-7 ligands on pathogenic peptides, Siglec-7 ligands expressed on macrophages, Siglec-7 ligands expressed on tumor-associated macrophages, Siglec-7 ligands expressed on neutrophils, Siglec-7 ligands expressed on monocytes, Siglec-7 ligands expressed on natural killer cells, Siglec-7 ligands expressed on T cells, Siglec-7 ligands expressed on T helper cells, Siglec-7 ligands expressed on cytotoxic T cells, Siglec-7 ligands expressed on B cells In some embodiments, the Siglec-7 ligands of the present disclosure are Siglec-7 ligands expressed on tumor-embedded immunosuppressive dendritic cells, Siglec-7 ligands expressed on tumor-embedded immunosuppressive macrophages, Siglec-7 ligands expressed on tumor-embedded immunosuppressive neutrophils, Siglec-7 ligands expressed on tumor-embedded immunosuppressive NK cells, Siglec-7 ligands expressed on myeloid-derived suppressor cells, Siglec-7 ligands expressed on myeloid-derived immunosuppressive cells, and Siglec-7 ligands expressed on regulatory T cells. In some embodiments, the Siglec-7 ligands of the present disclosure are gangliosides (e.g., disialogangliosides). Disialogangliosides generally have a lacto-ceramide core and one or more sialic acid residues.

[0132] Other examples of suitable ganglioside (e.g., disialoganglioside) ligands are listed in Table A. Generally, gangliosides (e.g., disialoganglioside) are molecules composed of glycosphingolipids with one or more sialic acids (e.g., n-acetyl-neuraminic acid, NANA) attached to a sugar chain.

[0133] Table A: Structures of exemplary ganglioside Siglec-7 ligands

[0134]

[0135]

[0136] Siglec-7 antibody

[0137] Certain aspects of the present disclosure relate to anti-Siglec-7 antibodies comprising one or more improved and / or enhanced functional features. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise one or more improved and / or enhanced functional features relative to a control antibody (e.g., a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 62). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a higher affinity for Siglec-7 (e.g., human Siglec-7) than a control anti-Siglec-7 antibody (e.g., a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 62). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure are administered at a half-maximal effective concentration (EC) lower than that of a control antibody (e.g., a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62). 50 ) binds to human cells, such as dendritic cells. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to human cells, such as dendritic cells, at a half-maximal effective concentration (EC) lower than that of a control antibody (e.g., a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62). 50 ) reduces the cellular levels (e.g., cell surface levels) of Siglec-7.

[0138] The cellular level of Siglec-7 may refer to, but is not limited to, the cell surface level of Siglec-7, the intracellular level of Siglec-7, and the total level of Siglec-7. In some embodiments, the reduction in the cellular level of Siglec-7 includes a reduction in the cell surface level of Siglec-7. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure that reduce the cellular level of Siglec-7 (e.g., the cell surface level of Siglec-7) have one or more of the following characteristics: (1) inhibiting or reducing one or more Siglec-7 activities; (2) inhibiting or reducing the ability of Siglec-7 to bind to one or more of its ligands; (3) reducing the expression of Siglec-7 in cells expressing Siglec-7; (4) the ability to interact with, bind to, or recognize Siglec-7 proteins; (5) the ability to specifically interact or bind to Siglec-7 proteins; and (6) the ability to treat, improve, or prevent any aspect of the diseases or conditions described or considered herein.

[0139] The anti-Siglec-7 antibodies of the present disclosure may have nanomolar or even picomolar affinities for the target antigen (e.g., human Siglec-7). In certain embodiments, the dissociation constant (K D ) is from about 0.001 nM to about 124 nM. In certain embodiments, the K D In certain embodiments, the K of the antibody is about 0.001 nM to about 54.1 nM. D In certain embodiments, the K of the antibody is about 0.10 nM to about 2.2 nM. D In some embodiments, the K of the antibody is about 0.198 nM to about 0.740 nM. D Less than or equal to about 130nM, 120nM, 110nM, 100nM, 90nM, 80nM, 70nM, 60nM, 50nM, 40nM, 30nM, 20nM, 10nM, 9.5nM, 9nM, 8.5nM, 8nM, 7.5nM, 7nM, 6.5nM, 6nM, 5.5nM, 5nM, 4.5nM, 4 In some embodiments, the antibody has a K of 0.05nM, 0.01nM, 0.05nM, 0.004nM, 0.003nM, 0.002nM, or 0.001nM. D Less than about 46.3 nM. In some embodiments, the antibody has a K DGreater than or equal to about 0.001 nM, .005 nM, .01 nM, .05 nM, 0.1 nM, 0.2 nM, 0.3 nM, 0.4 nM, 0.5 nM, 0.6 nM, 0.7 nM, 0.8 nM, 0.9 nM, 1 nM, 1.5 nM, 2 nM, 2.5 nM, 3 nM 3.5 nM, 4 nM, 4.5 nM, 5 nM, 5.5 nM, 6 nM, 6.5 nM, 7 nM, 7.5 nM, 8 nM, 8.5 nM, 9 nM, 9.5 nM, 10 nM, 20 nM, 30 nM, 40 nM, 50 nM, 60 nM, 70 nM, 80 nM, 90 nM, 100 nM, 110 nM, or 120 nM. That is, the K of the antibody D The molecule may have a molecular weight of about 130 nM, 120 nM, 110 nM, 100 nM, 90 nM, 80 nM, 70 nM, 60 nM, 50 nM, 40 nM, 30 nM, 20 nM, 10 nM, 9.5 nM, 9 nM, 8.5 nM, 8 nM, 7.5 nM, 7 nM, 6.5 nM, 6 nM, 5.5 nM, 5 nM, 4.5 nM, 4 nM. .004 nM, .003 nM, .002 nM, or .001 nM. Limit and about 0.001nM, 0.005nM, 0.01nM, 0.05nM, 0.1nM, 0.2nM, 0.3nM, 0.4nM, 0.5nM, 0.6nM, 0.7nM, 0.8nM, 0.9nM, 1nM, 1.5nM, 2nM, 2.5nM, 3nM, 3.5nM, 4nM, 4.5nM, 5nM, 5.5nM, 6nM In some embodiments, the antibody has a K of 100, 110, 120, 240, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, or 1200 nM, wherein the lower limit is lower than the upper limit. DIt is any of about 10 nM, about 9 nM, about 8 nM, about 7 nM, about 6 nM, about 5 nM, about 4 nM, about 3 nM, about 2 nM, about 1 nM, about 900 pM, about 800 pM, about 700 pM, about 600 pM, about 500 pM, about 400 pM, about 300 pM, about 200 pM, about 100 pM, about 90 pM, about 80 pM, about 70 pM, about 60 pM, about 50 pM, about 40 pM, about 30 pM, about 20 pM, about 10 pM, about 9 pM, about 8 pM, about 7 pM, about 6 pM, about 5 pM, about 4 pM, about 3 pM, about 2 pM, or about 1 pM.

[0140] In some embodiments, the K of the antibody is D Equal to about 0.198nM.

[0141] Various methods of measuring antibody affinity are known in the art, including, for example, using surface plasmon resonance or biolayer interferometry (see, e.g., Example 1, below). In some embodiments, the K for Siglec-7 is D The assay is performed at a temperature of approximately 25° C. In some embodiments, the K for Siglec-7 is D The assay is performed at a temperature of approximately 4° C. In some embodiments, K is determined using a monovalent antibody (e.g., Fab) or a monovalent full-length antibody. D In some embodiments, bivalent antibodies and monomeric recombinant Siglec-7 proteins are used to determine K D .

[0142] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a lower dissociation constant (K) for Siglec-7 than a control anti-Siglec-7 antibody (e.g., a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62; and / or a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50). D In some embodiments, the K of the anti-Siglec-7 antibodies of the present disclosure to the target (e.g., human Siglec-7) is D Compared with the K of the control anti-Siglec-7 antibody to the target DIn some embodiments, the K of an anti-Siglec-7 antibody of the present disclosure for a target (e.g., human Siglec-7) is lower than that of an anti-Siglec-7 antibody (e.g., a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62; and / or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50). D Compared with the K of the control anti-Siglec-7 antibody to the target D (For example, a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62; and / or a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: fold, at least about 1.1 fold, at least about 1.5 fold, at least about 2 fold, at least about 3 fold, at least about 4 fold, at least about 5 fold, at least about 6 fold, at least about 7 fold, at least about 8 fold, at least about 9 fold, at least about 10 fold, at least about 12.5 fold, at least about 15 fold, at least about 17.5 fold, at least about 20 fold, at least about 22.5 fold, at least about 25 fold, at least about 27.5 fold, at least about 30 fold, at least about 50 fold, at least about 100 fold, at least about 200 fold, at least about 300 fold, at least about 400 fold, at least about 500 fold, at least about 600 fold, at least about 700 fold, at least about 800 fold, at least about 900 fold, or at least about 1000 fold.

[0143] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a K for human Siglec-7 that is at least 100-fold lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. DIn some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a K for human Siglec-7 that is at least 50-fold lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. D In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a K for human Siglec-7 that is at least 10-fold lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. D In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a K for human Siglec-7 that is at least 5-fold lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. D In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a K for human Siglec-7 that is at least 2-fold lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. D .

[0144] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a K for human Siglec-7 that is at least 5.3 times lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. D .

[0145] In some embodiments, affinity is measured by surface plasmon resonance. In some embodiments, affinity is measured by biolayer interferometry. In some embodiments, affinity is measured at a temperature of about 25° C. In some embodiments, affinity is measured at a temperature of about 4° C. In some embodiments, affinity is measured using the experimental method described in Example 1 below.

[0146] The anti-Siglec-7 antibodies of the present disclosure can be used at half-maximal effective concentrations (EC 50 In certain embodiments, the EC of the antibody is 50In certain embodiments, the EC of the antibody is about 0.1 pM to about 25.4 nM. 50 In certain embodiments, the EC of the antibody is about 30 pM to about 25.4 nM. 50 In certain embodiments, the EC of the antibody is about 33.2 pM to about 25.4 nM. 50 In certain embodiments, the EC of the antibody is about 33.2 pM to about 3.0 nM. 50 In certain embodiments, the EC of the antibody is about 33.2 pM to about 1.0 nM. 50 In certain embodiments, the EC of the antibody is about 33.2 pM to about 500 pM. 50 In certain embodiments, the EC of the antibody is about 33.2 pM to about 400 pM. 50 In certain embodiments, the EC of the antibody is about 33.2 pM to about 300 pM. 50 In certain embodiments, the EC of the antibody is about 33.2 pM to about 200 pM. 50 It is about 33.2 pM to about 100 pM.

[0147] In some embodiments, the EC of the antibody 50 Less than about or equal to about 500 pM, 475 pM, 450 pM, 425 pM, 400 pM, 375 pM, 350 pM, 325 pM, 300 pM, 275 pM, 250 pM, 225 pM, 200 pM, 175 pM, 150 pM, 125 pM, 100 pM, 90 pM, 80 pM, 70 pM, 60 pM, 50 pM, 40 pM, 30 pM, 20 pM, 10 pM, 1 pM or 0.5 pM.

[0148] In some embodiments, the EC of the antibody 50 Less than about 447.0 pM. In some embodiments, the EC of the antibody 50 greater than or equal to about 0.1 pM, 0.5 pM, 1 pM, 10 pM, 20 pM, 30 pM, 40 pM, 50 pM, 60 pM, 70 pM, 80 pM, 90 pM, 100 pM, 125 pM, 150 pM, 175 pM, 200 pM, 225 pM, 250 pM, 275 pM, 300 pM, 325 pM, 350 pM, 375 pM, 400 pM or 425 pM. That is, the EC of the antibody 50The present invention may have an upper limit of about 425pM, 400pM, 375pM, 350pM, 325pM, 300pM, 275pM, 250pM, 225pM, 200pM, 175pM, 150pM, 125pM, 100pM, 90pM, 80pM, 70pM, 60pM, 50pM, 40pM, 30pM, 20pM, 10pM, 1pM or 0.5pM and an upper limit of about 0.1pM, 0. In some embodiments, the EC of the antibody is any one of a range of independently selected lower limits of 5pM, 1pM, 10pM, 20pM, 30pM, 40pM, 50pM, 60pM, 70pM, 80pM, 90pM, 100pM, 125pM, 150pM, 175pM, 200pM, 225pM, 250pM, 275pM, 300pM, 325pM, 350pM, 375pM or 400pM, wherein the lower limit is less than the upper limit. 50 is about 1pM, 2pM, 3pM, 4pM, 5pM, 6pM, 7pM, 8pM, 9pM, 10pM, 15pM, 20pM, 25pM, 30pM, 35pM, 40pM, 45pM, 50pM, 55pM, 60pM, 65pM, 70pM, 75pM, 80pM, 85pM, 90pM, 95pM, 1 any of 100 pM, 105 pM, 110 pM, 115 pM, 120 pM, 125 pM, 130 pM, 135 pM, 140 pM, 145 pM, 150 pM, 155 pM, 160 pM, 165 pM, 170 pM, 175 pM, 180 pM, 185 pM, 190 pM, 195 pM or 200 pM.

[0149] In some embodiments, the EC of the antibody 50 It is about 61.2pM.

[0150] Measuring antibody EC 50 Various methods of measuring EC values ​​are known in the art, including, for example, measurement by flow cytometry (see, e.g., Example 2, below). In some embodiments, EC values ​​are measured in vitro using primary human dendritic cells. 50 In some embodiments, EC is measured in vitro using primary human monocytes. 50 In some embodiments, EC is measured in vitro using primary human macrophages. 50 In some embodiments, EC is measured in vitro using cultured cells transfected with human Siglec-7. 50 In some embodiments, EC is measured at a temperature of about 4°C. 50 In some embodiments, EC is measured at a temperature of about 25°C. 50In some embodiments, EC is measured at a temperature of approximately 35°C. 50 In some embodiments, EC is measured at a temperature of approximately 37°C. 50 In some embodiments, EC is determined using a monovalent antibody (eg, Fab) or a monovalent form of a full-length antibody. 50 In some embodiments, EC is determined using antibodies containing constant regions that exhibit enhanced Fc receptor binding. 50 In some embodiments, EC is determined using antibodies containing constant regions that exhibit reduced Fc receptor binding. 50 .

[0151] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a higher potency in reducing cell surface levels of Siglec-7 relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 61 and a light chain variable region comprising the sequence of SEQ ID NO: 62, or relative to an anti-Siglec-7 antibody having a heavy chain variable region comprising the sequence of SEQ ID NO: 38 and a light chain variable region comprising the sequence of SEQ ID NO: 50. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have a lower EC than a control anti-Siglec-7 antibody (e.g., a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62; and / or a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50). 50 Reduction of cellular levels (e.g., cell surface levels) of Siglec-7 (e.g., as measured in vitro using primary human dendritic cells). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure are more effective than the EC of a control anti-Siglec-7 antibody (e.g., a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62; and / or a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50). 50The EC of at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% is lower. 50 Reducing the cellular level (e.g., cell surface level) of Siglec-7. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure are more efficacious than the EC of a control anti-Siglec-7 antibody (e.g., a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62; and / or a control anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50). 50 An EC at least about 1 fold, at least about 1.1 fold, at least about 1.5 fold, at least about 2 fold, at least about 3 fold, at least about 4 fold, at least about 5 fold, at least about 6 fold, at least about 7 fold, at least about 8 fold, at least about 9 fold, at least about 10 fold, at least about 12.5 fold, at least about 15 fold, at least about 17.5 fold, at least about 20 fold, at least about 22.5 fold, at least about 25 fold, at least about 27.5 fold, at least about 30 fold, at least about 50 fold, or at least about 100 fold lower. 50 Reduce the cellular level (e.g., cell surface level) of Siglec-7. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have an EC at least 30.8 times lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62. 50 In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have an EC of at least 10.2 times lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. 50 In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have an EC at least 16.7-fold lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62. 50In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have an EC of at least 5.6 times lower than that of an anti-Siglec-7 antibody having a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 50. 50 In some embodiments, EC is measured in vitro using primary human dendritic cells. 50 In some embodiments, EC is measured in vitro using primary human monocytes. 50 In some embodiments, EC is measured in vitro using primary human macrophages. 50 In some embodiments, EC is measured in vitro using cultured cells transfected with human Siglec-7. 50 In some embodiments, EC is measured by flow cytometry. 50 In some embodiments, EC is measured at a temperature of about 25°C. 50 In some embodiments, EC is measured at a temperature of approximately 35°C. 50 In some embodiments, EC is measured at a temperature of approximately 37°C. 50 In some embodiments, EC is determined using antibodies containing constant regions that exhibit enhanced Fc receptor binding. 50 In some embodiments, EC is determined using antibodies containing constant regions that exhibit reduced Fc receptor binding. 50 In some embodiments, EC is measured using the experimental method described in Example 2 below. 50 .

[0152] Any in vitro cell-based assay or suitable in vivo model described herein or known in the art can be used to measure inhibition or reduction of the interaction (e.g., binding) between Siglec-7 and one or more Siglec-7 ligands. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure inhibit or reduce the interaction (e.g., binding) between Siglec-7 and one or more Siglec-7 ligands by reducing Siglec-7 expression (e.g., by reducing cell surface expression of Siglec-7). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure inhibit or reduce the interaction (e.g., binding) between Siglec-7 and one or more Siglec-7 ligands by at least 21%, at least 22%, at least 23%, at least 24%, at least 25%, at least 26%, at least 27%, at least 28%, at least 29%, at least 30%, at least 31%, at least 32%, at least 33%, at least 34%, at least 35%, at least 36%, at least 37%, at least 38%, at least 39%, at least 40%, at least 41%, at least 42%, at least 43%, at least 44%, at least 45%, at least 46%, at least 47%, at least 48%, at least 49%, at least 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least %, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more.

[0153] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure inhibit cell surface clustering of Siglec-7. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure inhibit one or more activities of Siglec-7 proteins, including but not limited to, counteracting one or more phosphorylations of Tyr-437 and Tyr-460 by Src family tyrosine kinases such as Syk, LCK, FYM and / or ZAP70; recruiting and binding to tyrosine-specific protein phosphatases SHP1 and SHP2; recruiting and binding to PLC-γ1, which acts as a guanine nucleotide exchange factor for dynamin-1; recruiting and binding to SH2 domain-containing proteins (e.g., Crk1); recruiting and binding to spleen tyrosine kinase Syk; recruiting and binding to SH3-SH2-SH3 growth factor receptors. Grb2; recruits and binds to multiple SH2-containing proteins; phosphorylates Ser-307 and Ser-342 via protein kinase C; regulates expression of one or more anti-inflammatory cytokines IL-4, IL-10, IL-13, IL-35, IL-16, TGF-β, IL-1Ra, G-CSF, and soluble receptors for TNF, IFN-β1a, IFN-β1b, or IL-6 in monocytes, macrophages, T cells, dendritic cells, neutrophils, and / or microglia; reduces intracellular calcium mobilization; regulates monocytes, macrophages, T cells, dendritic cells, neutrophils, and / or microglia one or more proinflammatory cytokines IFN-a4, IFN-b, IL-1β, TNF-α, IL-6, IL-8, CRP, IL-20 family members, LIF, IFN-γ, OSM, CNTF, GM-CSF, IL-11, IL-12, IL-17, IL-18, IL-23, CXCL10, IL-33, CRP, IL-33, MCP-1 and MIP-1-β; regulate the expression of one or more proteins selected from the following: C1qa, C1qB, C1qC, C1s, C1R, C4, C2, C3, ITGB2, HMOX1, LAT2, CASP1, CS TA, VSIG4, MS4A4A, C3AR1, GPX1, TyroBP, ALOX5AP, ITGAM, SLC7A7, CD4, ITGAX, PYCARD, CD14, CD16, HLA-DR, and CCR2; inhibit extracellular signal-regulated kinase (ERK) phosphorylation; reduce tyrosine phosphorylation on multiple cellular proteins; regulate CC chemokine receptor 7 (CCR7) expression; inhibit microglial chemotaxis towards CCL19-expressing cells and CCL21-expressing cells; activate phosphoinositide 3-kinase; reduce cell growth of monocytes, macrophages, T cells, dendritic cells, and / or microglia;Reduces T cell proliferation induced by dendritic cells, bone marrow-derived dendritic cells, monocytes, microglia, M1 microglia, activated M1 microglia, M2 microglia, macrophages, M1 macrophages, activated M1 macrophages, and / or M2 macrophages; inhibits osteoclast production, reduces the rate of osteoclast formation, or both; reduces neutrophils, dendritic cells, bone marrow-derived dendritic cells, macrophages, M1 macrophages, activated M1 macrophages, M2 macrophages, monocytes, osteoclasts, T cells, T helper cells, cytotoxic T cells, granulocytes, microglia, M1 microglia, activated M1 microglia, and / or M2 microglia cell survival; reduce the proliferation of neutrophils, dendritic cells, bone marrow-derived dendritic cells, macrophages, M1 macrophages, activated M1 macrophages, M2 macrophages, monocytes, osteoclasts, T cells, T helper cells, cytotoxic T cells, granulocytes, microglia, M1 microglia, activated M1 microglia and / or M2 microglia; inhibit the proliferation of neutrophils, dendritic cells, bone marrow-derived dendritic cells, macrophages, M1 macrophages, activated M1 macrophages, M2 macrophages, monocytes, osteoclasts, T cells, T helper cells, cytotoxic T cells, granulocytes, microglia, M1 microglia, activated M1 microglia and / or M2 microglia; reduce one or more functions of neutrophils, dendritic cells, bone marrow-derived dendritic cells, macrophages, M1 macrophages, activated M1 macrophages, M2 macrophages, monocytes, osteoclasts, T cells, T helper cells, cytotoxic T cells, granulocytes, microglia, M1 microglia, activated M1 microglia and / or M2 microglia; inhibit neutrophils, dendritic cells, bone marrow-derived dendritic cells, macrophages, M1 macrophages, activated M1 macrophages, M2 macrophages, monocytes, osteoclasts, T cells, T helper cells, cytotoxic T cells, granulocytes, microglia, M1 microglia, activated M1 microglia and / or M2 microglia Maturation of activated M1 microglia and / or M2 microglia; Increased cell death and apoptosis of monocytes, macrophages, T cells, dendritic cells, neutrophils and / or microglia; Reduced phagocytic activity of monocytes, macrophages, T cells, dendritic cells, neutrophils and / or microglia; Reduced proliferation of monocytes, macrophages, T cells, dendritic cells, neutrophils and / or microglia; Reduced overall function of monocytes, macrophages, T cells, dendritic cells, neutrophils and / or microglia; Phosphorylation of ITAM-containing receptors; Phosphorylation of signaling molecules that mediate ITAM signaling; Reduced activation of pattern recognition receptors;Reducing the activation of Toll-like receptors; reducing the activation of damage-related clearance of cell debris and protein fragments; interaction between Siglec-7 and one or more of its ligands; interaction between Siglec-7 and co-receptors; reducing one or more types of clearance selected from apoptotic neurons, neural tissue debris, dysfunctional synaptic clearance, non-neural tissue debris, bacteria or other foreign matter, pathogenic protein clearance and tumor cell clearance; inhibiting apoptotic neurons, neural tissue debris, non-neural tissue debris, bacteria, other foreign matter, pathogenic proteins, pathogenic peptides, pathogenic nuclei phagocytosis of one or more of the above-mentioned proteins; inhibiting the clearance of pathogenic nucleic acids, such as antisense GGCCCC (G2C4) repeat sequence expansion RNA; activating the clearance of pathogenic proteins, wherein the pathogenic proteins are selected from amyloid beta, amyloid beta plaques, amyloid precursor protein or fragments thereof, Tau, IAPP, α-synuclein, TDP-43, FUS protein, C9orf72 (chromosome 9 open reading frame 72), c9RAN protein, prion protein, PrPSc, huntingtin protein, calcitonin, superoxide dismutase, Ataxin, Ataxin 1, Ataxin 2, Ataxin 3, Ataxin 7, Ataxin 8, Ataxin 10, Lewy bodies, atrial natriuretic factor, islet amyloid polypeptide, insulin, apolipoprotein AI, serum amyloid A, interferon, prolactin, transthyretin, lysozyme, β2 microglobulin, gelsolin, corneal epithelial protein, cysteine ​​protease inhibitor, immunoglobulin light chain AL, S-IBM protein, repeat-associated non-ATG (RAN) translation product, dipeptide repeat (DPR) peptide, Glycine-Alanine (GA) repeat peptides, Glycine-Proline (GP) repeat peptides, Glycine-Arginine (GR) repeat peptides, Proline-Alanine (PA) repeat peptides, Ubiquitin, and Proline-Arginine (PR) repeat peptides; inhibiting beneficial immune responses to different types of cancer selected from the group consisting of bladder cancer, brain cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, renal cell carcinoma, renal pelvis cancer, leukemia, lung cancer, melanoma, non-Hodgkin's lymphoma, acute myeloid leukemia, pancreatic cancer, prostate cancer, ovarian cancer, fibrosarcoma, and thyroid cancer;Suppressing a beneficial immune response to a different type of neurological disorder selected from the group consisting of dementia, frontotemporal dementia, Alzheimer's disease, vascular dementia, mixed dementia, Creutzfeldt-Jakob disease, normal pressure hydrocephalus, amyotrophic lateral sclerosis, Huntington's disease, taupathy, Nasu-Hakoladisease, stroke, acute trauma, chronic trauma, essential tremor, Behcet's disease, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, Shy-Drager syndrome syndrome), progressive supranuclear palsy, corticobasal degeneration, acute disseminated encephalomyelitis, granulomatous disorders, sarcoidosis, diseases of aging, epilepsy, spinal cord injury, traumatic brain injury, age-related macular degeneration, glaucoma, retinitis pigmentosa, retinal degeneration, and multiple sclerosis; inhibition of beneficial immune responses to different types of inflammatory and infectious disorders selected from lupus, acute and chronic colitis, wound healing, Crohn's disease, inflammatory bowel disease, ulcerative colitis, obesity, malaria, respiratory tract infections, sepsis, eye infections, systemic infections, lupus, arthritis, low bone density, osteoporosis, osteogenesis, osteopetrosis, and Paget's disease of bone bone); binds to a Siglec-7 ligand on tumor cells; binds to a Siglec-7 ligand on dendritic cells, bone marrow-derived dendritic cells, monocytes, microglia, T cells, neutrophils and / or macrophages; inhibits tumor cell killing by one or more of the following: microglia, macrophages, dendritic cells, bone marrow-derived dendritic cells, neutrophils, T cells, T helper cells or cytotoxic T cells; inhibits the anti-tumor cell proliferation activity of one or more of the following: microglia, macrophages, dendritic cells, bone marrow-derived dendritic cells, neutrophils, T cells, T helper cells or cytotoxic T cells Myeloid-derived dendritic cells, neutrophils, T cells, T helper cells, or cytotoxic T cells; inhibit the anti-tumor cell metastatic activity of one or more of the following: microglia, macrophages, dendritic cells, bone marrow-derived dendritic cells, neutrophils, T cells, T helper cells, or cytotoxic T cells; promote immunosuppressive dendritic cells, immunosuppressive macrophages, myeloid-derived suppressor cells, tumor-associated macrophages, or regulatory T cells; inhibit one or more receptors containing ITAM motifs, such as TREM1, TREM2, FcγR, DAP10, and DAP12;Inhibits the presence of the motif D / Ex0–2YxxL / IX6–8YxxL / I (SEQ ID NO:67); inhibiting signaling through one or more pattern recognition receptors (PRRs), such as receptors that recognize pathogen-associated molecular patterns (PAMPs) and receptors that recognize damage-associated molecular patterns (DAMPs); inhibiting signaling through one or more Toll-like receptors; inhibiting the JAK-STAT signaling pathway; inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB); inhibiting PLCγ / PKC / calcium mobilization; inhibiting PI3K / Akt, Ras / MAPK signaling; reducing the expression of one or more inflammatory receptors (such as CD86) expressed on one or more of microglia, macrophages, dendritic cells, bone marrow-derived dendritic cells, neutrophils, T cells, T helper cells, or cytotoxic T cells; increasing the expression of one or more Siglec-7-dependent genes; normalizing the expression of disrupted Siglec-7-dependent genes; and reducing the expression of one or more ITAM-dependent genes (such as NFAT transcription factors).

[0154] In some embodiments, the anti-Siglec-7 antibody inhibits the interaction (e.g., binding) between the Siglec-7 protein of the present disclosure and one or more Siglec-7 ligands, including but not limited to Siglec-7 ligands expressed on erythrocytes, Siglec-7 ligands expressed on bacterial cells, Siglec-7 ligands expressed on apoptotic cells, Siglec-7 ligands expressed on tumor cells, Siglec-7 ligands expressed on viruses, Siglec-7 ligands expressed on dendritic cells, Siglec-7 ligands expressed on neural cells, Siglec-7 ligands expressed on glial cells, Siglec-7 ligands expressed on microglial cells, Siglec-7 ligands expressed on astrocytes, Siglec-7 ligands on β-amyloid plaques, Siglec-7 ligands on Tau tangles, Siglec-7 ligands on pathogenic proteins, and Siglec-7 on pathogenic peptides. ligands, Siglec-7 ligands expressed on macrophages, Siglec-7 ligands expressed on natural killer cells, Siglec-7 ligands expressed on T cells, Siglec-7 ligands expressed on T helper cells, Siglec-7 ligands expressed on cytotoxic T cells, Siglec-7 ligands expressed on B cells, Siglec-7 ligands expressed on tumor-embedded immunosuppressive dendritic cells, Siglec-7 ligands expressed on tumor-embedded immunosuppressive macrophages Siglec-7 ligand, Siglec-7 ligand expressed on myeloid-derived suppressor cells, Siglec-7 ligand expressed on regulatory T cells, secreted mucin, sialic acid, sialic acid-containing glycolipids, sialic acid-containing glycoproteins, alpha-2,6-linked sialic acid-containing glycolipids, alpha-2,6-linked sialic acid-containing glycoproteins, alpha-2,3-linked sialic acid-containing glycolipids, alpha-2,3-linked sialic acid-containing glycoproteins, alpha-1 acid glycoprotein (AGP), CD24 protein, and gangliosides.

[0155] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to the Siglec-7 proteins of the present disclosure expressed on the cell surface, and the naked antibodies inhibit the interaction (e.g., binding) between the Siglec-7 proteins and one or more Siglec-7 ligands. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure that bind to the Siglec-7 proteins of the present disclosure inhibit the interaction (e.g., binding) between the Siglec-7 proteins and one or more Siglec-7 ligands by reducing the effective level of Siglec-7 available for interacting with these proteins on the cell surface or within the cell. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure that bind to the Siglec-7 proteins of the present disclosure inhibit the interaction (e.g., binding) between the Siglec-7 proteins and one or more Siglec-7 ligands by inducing degradation of Siglec-7.

[0156] As used herein, the level of Siglec-7 may refer to the expression level of a gene encoding Siglec-7; the expression level of one or more transcripts encoding Siglec-7; the expression level of Siglec-7 protein; and / or the amount of Siglec-7 protein present in a cell and / or on the cell surface. Any known method in the art for measuring the level of gene expression, transcription, translation, and / or protein abundance or localization can be used to determine the level of Siglec-7.

[0157] In addition, the anti-Siglec-7 antibodies of the present disclosure can be used to prevent, reduce the risk of, or treat the following diseases: dementia, frontotemporal dementia, Alzheimer's disease, vascular dementia, mixed dementia, Creutzfeldt-Jakob disease, normal pressure hydrocephalus, amyotrophic lateral sclerosis, Huntington's disease, Tauopathy, Nasu-Hakora disease, stroke, acute trauma, chronic trauma, lupus, acute and chronic colitis, rheumatoid arthritis, wound healing, Crohn's disease, inflammatory bowel disease , ulcerative colitis, obesity, malaria, essential tremor, central nervous system lupus, Behçet's disease, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, Shy-Drago syndrome, progressive supranuclear palsy, corticobasal degeneration, acute disseminated encephalomyelitis, granulomatous disorders, sarcoidosis, aging diseases, epilepsy, spinal cord injury, traumatic brain injury, age-related macular degeneration, glaucoma, retinitis pigmentosa, retinal degeneration, respiratory tract infection, sepsis, eye infection, systemic infection, wolf sores, arthritis, multiple sclerosis, low bone density, osteoporosis, osteogenesis, osteopetrosis, Paget's disease of bone, cancer (including bladder cancer, brain cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, renal cell carcinoma, renal pelvis cancer, leukemia, lung cancer, melanoma, non-Hodgkin's lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, fibrosarcoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), Leukemia (CML), multiple myeloma, polycythemia vera, essential thrombocythemia, primary or idiopathic myelofibrosis, primary or idiopathic myelosclerosis, bone marrow-derived tumors, tumors expressing Siglec-7, thyroid cancer), infection, CNS herpes, parasitic infection, trypanosome infection, Wolbachia infection, Pseudomonas aeruginosa infection, Leishmania donovani infection, group B Streptococcus infection, Campylobacter jejuni infection, Neisseria meningitidis infection, HIV type 1 and / or Haemophilus influenzae. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure can be used to induce or promote the survival, maturation, functionality, migration or proliferation of one or more immune cells in an individual in need thereof; or to reduce the activity, functionality or survival of the following in an individual in need thereof: regulatory T cells, tumor-embedded immunosuppressive dendritic cells, tumor-embedded immunosuppressive macrophages, myeloid-derived suppressor cells, tumor-associated macrophages, acute myeloid leukemia (AML) cells, chronic lymphocytic leukemia (CLL) cells and / or chronic myeloid leukemia (CML) cells. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure are monoclonal antibodies.

[0158] In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure reduce the cellular level of Siglec-7 (e.g., cell surface level, intracellular level, and / or total level). In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure induce the downregulation of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure induce the cleavage of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure induce the internalization of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure induce the shedding of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure induce the degradation of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure induce the desensitization of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure act as ligand mimics to transiently activate Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure act as ligand mimics and transiently activate Siglec-7 before inducing a decrease in the cellular level of Siglec-7 and / or inhibiting the interaction (e.g., binding) between Siglec-7 and one or more Siglec-7 ligands. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure act as ligand mimics and transiently activate Siglec-7 before inducing the degradation of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure act as ligand mimics and transiently activate Siglec-7 before inducing the cleavage of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure act as ligand mimics and transiently activate Siglec-7 before inducing the internalization of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure act as ligand mimics and transiently activate Siglec-7 before inducing the shedding of Siglec-7. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure act as ligand mimetics and transiently activate Siglec-7 prior to inducing downregulation of Siglec-7 expression. In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure act as ligand mimetics and transiently activate Siglec-7 prior to inducing desensitization of Siglec-7.

[0159] In some embodiments, the isolated anti-Siglec-7 antibodies of the present disclosure are human antibodies, humanized antibodies, bispecific antibodies, monoclonal antibodies, multivalent antibodies, or chimeric antibodies. Exemplary descriptions of such antibodies are found throughout the present disclosure.

[0160] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to human Siglec-7 or a homolog thereof, including but not limited to mammalian Siglec-7 proteins or non-human primate Siglec-7 proteins. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure specifically bind to human Siglec-7. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to human Siglec-7 and do not cross-react with Siglec-7 orthologs or homologs from other species.

[0161] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to the Siglec-7 protein of the present disclosure expressed on the cell surface and, after binding to the surface-expressed Siglec-7 protein, modulate (e.g., induce or inhibit) one or more Siglec-7 activities of the present disclosure. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure are inert antibodies.

[0162] Exemplary Antibodies Against Siglec-7

[0163] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to an epitope of human Siglec-7 that is identical to or overlaps with the Siglec-7 epitope bound by an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to substantially the same Siglec-7 epitope bound by an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62.

[0164] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure competitively inhibit the binding of an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure compete for binding to Siglec-7 with an anti-Siglec-7 antibody comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 61 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 62.

[0165] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure competitively inhibit the binding of at least one antibody selected from any of the antibodies listed in Tables 1-5, 6A-6C, 7A-7C, 8A-8D, 9A-9D, 10, and 11. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure competitively inhibit the binding of at least one antibody comprising a heavy chain variable region and a light chain variable region selected from the group consisting of S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7 -H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H 8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB -H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S 7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45 , S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB- H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.2 and any combination thereof.

[0166] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure compete for binding to Siglec-7 with one or more antibodies comprising a heavy chain variable region and a light chain variable region selected from the group consisting of S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8 8. S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7 AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7A B-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H 8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.2 and any combination thereof, wherein the anti-Siglec-7 antibody reduces binding of a competing anti-Siglec-7 antibody described herein to Siglec-7 by an amount in the range of about 50% to 100% compared to binding to Siglec-7 in the absence of the anti-Siglec-7 antibody as measured by surface plasmon resonance.In some embodiments, an anti-Siglec-7 antibody of the present disclosure competes with one or more antibodies for binding to Siglec-7, wherein the anti-Siglec-7 antibody reduces binding of one or more competing anti-Siglec-7 antibodies described herein by at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or 100%, compared to binding to Siglec-7 in the absence of the anti-Siglec-7 antibody, as measured by surface plasmon resonance.

[0167] In some embodiments, an anti-Siglec-7 antibody of the present disclosure reduces the binding of one or more competing anti-Siglec-7 antibodies to Siglec-7 by 100%, which means that the anti-Siglec-7 antibody substantially completely blocks the binding of one or more antibodies comprising a heavy chain variable region and a light chain variable region selected from the group consisting of S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H13, S7AB-H14, S7AB-H15, S7AB-H16, S7AB-H17, S7AB-H18, S7AB-H19, S7AB-H20, S7AB-H21, S7AB-H22, S7AB-H23, S7AB-H24, S7AB-H25, S7AB-H26, S7AB-H27, S7AB-H28, S7AB-H29, S7AB-H30, S7AB-H31, S7AB-H32, S7AB-H33, S7AB-H34, S7AB-H35, S7AB-H36, S7AB-H37, S7AB-H38, S7AB-H39, S7AB-H40, S7AB-H41, S7AB-H42, S7AB-H43, S7AB-H44, S7AB-H45, S7AB-H46, S7AB-H47, S7AB-H48, S7AB-H49, S7AB-H50, S7AB-H51, S7AB-H52, S7AB-H53, S7AB-H54, S7AB -H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8. 22. S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB -H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S 7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8. 30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.2 and any combination thereof.

[0168] In some embodiments, the composition is selected from the group consisting of S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S 7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7 AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB- H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.3 6. S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2 , S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8 .35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 and S7AB-H8.45.2, in competition assays corresponding to a 10:1 ratio, a 9:1 ratio, an 8:1 ratio, a 7:1 ratio, a 6:1 ratio, a 5:1 ratio, a 4:1 ratio, a 3:1 ratio, a 2:1 ratio, a 1:1 ratio, a 0.75:1 ratio, a 0.5:1 ratio, a 0.25:1 ratio, a 0.1:1 ratio, a 0.075:1 ratio, a 0.050:1 ratio, a 0.025:1 ratio, a 0.01:1 ratio, a 0.0075:1 ratio, a 0.010:1 ratio, a 0.015 ...0.050:1 ratio, 0.0025:1 ratio, 0.001: ratio, 0.00075:1 ratio, 0.00050:1 ratio, 0.00025:1 ratio, 0.0001: ratio, 1:10 ratio, 1:9 ratio, 1:8 ratio, 1:7 ratio, 1:6 ratio, 1:5 ratio, 1:4 ratio, 1:3 ratio, 1:2 ratio, 1:0.75 ratio, 1:0.5 ratio, 1:0.25 ratio, 1:0.1 ratio, 1:0 The amount of the antibody is present in a 1:0.075 ratio, a 1:0.050 ratio, a 1:0.025 ratio, a 1:0.01 ratio, a 1:0.0075 ratio, a 1:0.0050 ratio, a 1:0.0025 ratio, a 1:0.001 ratio, a 1:0.00075 ratio, a 1:0.00050 ratio, a 1:0.00025 ratio, or a 1:0.0001 ratio (anti-Siglec-7 antibodies of the present disclosure: competing anti-Siglec-7 antibodies described herein).

[0169] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure that compete with an antibody comprising a heavy chain variable region and a light chain variable region of an antibody selected from the group consisting of S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H13, S7AB-H14, S7AB-H15, S7AB-H16, S7AB-H17, S7AB-H18, S7AB-H19, S7AB-H20, S7AB-H21, S7AB-H22, S7AB-H23, S7AB-H24, S7AB-H25, S7AB-H26, S7AB-H27, S7AB-H28, S7AB-H29, S7AB-H30, S7AB-H31, S7AB-H32, S7AB-H33, S7AB-H34, S7AB-H35, S7AB-H36, S7AB-H37, S7AB-H38, S7AB-H39, S7AB-H40, S7AB-H41, S7AB-H42, S7AB-H43, S7AB-H44, S7AB-H45, S7AB-H46, S7AB-H47, S7AB-H48, S7AB-H49, S7AB-H50, S7AB-H51, S7AB-H52, S7AB-H53, S7AB-H54, S7AB-H55 7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S 7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB -H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8 .33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43 , S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S 7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.In some embodiments, the abundance of an anti-Siglec-7 antibody of the present disclosure is about 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 15-fold, 20-fold, 25-fold, 30-fold, 35-fold, 40-fold, 45-fold, 50-fold, 55-fold, 60-fold, 65-fold, 70-fold, 75-fold, 80-fold, 85-fold, 90-fold, 95-fold, or 100-fold greater than the amount of one or more competing anti-Siglec-7 antibodies described herein in a competition assay.

[0170] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to an epitope of human Siglec-7 that is identical to or overlaps with a Siglec-7 epitope bound by at least one antibody selected from any of the antibodies listed in Tables 1-5, 6A-6C, 7A-7C, 8A-8D, 9A-9D, 10, and 11. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to an epitope of human Siglec-7 that is identical to or overlaps with a Siglec-7 epitope bound by at least one antibody comprising a heavy chain variable region and a light chain variable region selected from the group consisting of: S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H13, S7AB-H14, S7AB-H15, S7AB-H16, S7AB-H17, S7AB-H18 AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8. 14. S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8. 24. S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8. 34. S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8. 44. S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8 .30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2.

[0171] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to substantially the same Siglec-7 epitope bound by at least one antibody selected from any of the antibodies listed in Tables 1-5, 6A-6C, 7A-7C, 8A-8D, 9A-9D, 10, and 11. In some embodiments, binding to "substantially the same Siglec-7 epitope" refers to binding to at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% of the amino acid residues in the epitope.

[0172] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure bind to substantially the same Siglec-7 epitope bound by at least one antibody comprising a heavy chain variable region and a light chain variable region selected from the group consisting of: S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H13, S7AB-H14, S7AB-H15, S7AB-H16, S7AB-H17, S7AB-H18, S7AB-H19, S7AB-H20, S7AB-H21, S7AB-H22, S7AB-H23, S7AB-H24, S7AB-H25 B-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H 8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB -H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7 AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8. 30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2. Detailed exemplary methods for mapping epitopes to which antibodies bind are provided in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology, Vol. 66 (Humana Press, Totowa, NJ).

[0173] Any suitable competition assay or Siglec-7 binding assay known in the art (e.g., BIAcore analysis, biolayer interferometry, ELISA assay, or flow cytometry) can be used to determine whether an anti-Siglec-7 antibody competes for binding to Siglec-7 with one or more antibodies selected from the group consisting of S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2 , S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.1 3. S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7 AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB- H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.4 4. S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2 , S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.2 and any combination thereof.

[0174] In an exemplary competition assay, immobilized Siglec-7 or cells expressing Siglec-7 on the cell surface are incubated in a solution comprising a first labeled antibody (e.g., human or non-human primate) that binds to Siglec-7 and a second unlabeled antibody that is being tested for its ability to compete with the first antibody for binding to Siglec-7. The second antibody may be present in the hybridoma supernatant. As a control, immobilized Siglec-7 or cells expressing Siglec-7 are incubated in a solution comprising the first labeled antibody but not the second unlabeled antibody. After incubation under conditions that allow the first antibody to bind to Siglec-7, excess unbound antibody is removed, and the amount of label associated with the immobilized Siglec-7 or cells expressing Siglec-7 is measured. If the amount of label associated with the immobilized Siglec-7 or cells expressing Siglec-7 is substantially reduced in the test sample relative to the control sample, then the second antibody is indicated to be competing with the first antibody for binding to Siglec-7. See Harlow and Lane (1988) Antibodies: A Laboratory Manual Chapter 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY).

[0175] Anti-Siglec-7 antibody light chain and heavy chain variable regions

[0176] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region comprising one or more (e.g., one or more, two or more, or all three) HVRs selected from HVR-H1, HVR-H2, and HVR-H3 (as shown in Tables 6A-6C). In some embodiments, the heavy chain variable region comprises HVR-H1, HVR-H2, and HVR-H3 (as shown in Tables 6A-6C).

[0177] In some embodiments, the HVR-H1 comprises a sequence according to Formula I: GYAFTX1X2WMN (SEQ ID NO: 6), wherein X1 is E, M, G, or A, and X2 is T, A, or Y. In some embodiments, the HVR-H1 comprises a sequence selected from SEQ ID NOs: 1-5. In some embodiments, the HVR-H2 comprises a sequence according to Formula II: RIFPGX1GHTN (SEQ ID NO: 9), wherein X1 is L or Y. In some embodiments, the HVR-H2 comprises a sequence selected from SEQ ID NOs: 7-8. In some embodiments, the HVR-H3 comprises a sequence of DYSDYYFDY (SEQ ID NO: 10).

[0178] In some embodiments, the heavy chain variable region comprises HVR-H1 according to Formula I, HVR-H2 according to Formula II, and HVR-H3 comprising the sequence of DYSDYYFDY (SEQ ID NO: 10). In some embodiments, the heavy chain variable region comprises HVR-H1 comprising a sequence selected from SEQ ID NOs: 1-5, HVR-H2 comprising a sequence selected from SEQ ID NOs: 7-8, and HVR-H3 comprising the sequence of SEQ ID NO: 10.

[0179] In some embodiments, the heavy chain variable region comprises antibodies S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H 8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7 AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.3 3. S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB- H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H 8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.2, and HVR-H1, HVR-H2, and HVR-H3 of any combination thereof (as shown in Tables 6A to 6C).

[0180] In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable region, wherein the heavy chain variable region comprises one or more of the following: (a) HVR-H1 comprising a heavy chain variable region that is identical to that of antibodies S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8. 16. S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7A B-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8 .44.2, S7AB-H8.45.1 or S7AB-H8.45.2 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the HVR-H1 amino acid sequence of antibody S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7. S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7A B-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H 8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.4 1. S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7 an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to an HVR-H2 amino acid sequence of S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, or S7AB-H8.45.2; and ( c) HVR-H3, said HVR-H3 comprising antibodies S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB -H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21. S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB -H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S 7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.4 1. S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB -H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2 , S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8. 44.2, S7AB-H8.45.1 or S7AB-H8.45.2 having an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the HVR-H3 amino acid sequence of S7AB-H8.45.2.

[0181] In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises HVR-H1 comprising the amino acid sequence GYAFTAAWMN (SEQ ID NO: 4); HVR-H2 comprising the amino acid sequence RIFPGLGHTN (SEQ ID NO: 7); and HVR-H3 comprising the amino acid sequence DYSDYYFDY (SEQ ID NO: 10).

[0182] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable region comprising one or more (e.g., one or more, two or more, or all three) HVRs selected from HVR-L1, HVR-L2, and HVR-L3 (as shown in Tables 7A-7C). In some embodiments, the light chain variable region comprises HVR-L1, HVR-L2, and HVR-L3 (as shown in Tables 7A-7C). In some embodiments, the antibody is not an antibody comprising a light chain variable region comprising HVR-L1 comprising the sequence of RASQDINTYLN (SEQ ID NO: 65); HVR-L2 comprising the sequence of YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising the sequence of QQGNTLPWT (SEQ ID NO: 20).

[0183] In some embodiments, the HVR-L1 comprises a sequence according to Formula III: RX1SX2DX3NTYLN (SEQ ID NO: 15), wherein X1 is G or A, X2 is Q or E, and X3 is I, T, or A. In some embodiments, the HVR-L1 comprises a sequence selected from SEQ ID NOs: 11-14. In some embodiments, the HVR-L2 comprises a sequence of YTSRLHS (SEQ ID NO: 16). In some embodiments, the HVR-L3 comprises a sequence according to Formula IV: QX1GX2X3X4PWT (SEQ ID NO: 24), wherein X1 is Q or G, X2 is N or G, X3 is L, T, V, or I, and X4 is L or K. In some embodiments, the HVR-L3 comprises a sequence selected from SEQ ID NOs: 17-23.

[0184] In some embodiments, the light chain variable region comprises HVR-L1 according to Formula III, HVR-L2 comprising the sequence of YTSRLHS (SEQ ID NO: 16), and HVR-L3 according to Formula IV, and the antibody is not an antibody comprising a light chain variable region comprising HVR-L1 comprising the sequence of RASQDINTYLN (SEQ ID NO: 65); HVR-L2 comprising the sequence of YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising the sequence of QQGNTLPWT (SEQ ID NO: 20). In some embodiments, the light chain variable region comprises an HVR-L1 comprising a sequence selected from the group consisting of SEQ ID NOs: 11-14, an HVR-L2 comprising a sequence selected from the group consisting of YTSRLHS (SEQ ID NO: 16), and an HVR-L3 comprising a sequence selected from the group consisting of SEQ ID NOs: 17-23, and the antibody is not an antibody comprising a light chain variable region comprising an HVR-L1 comprising the sequence of RASQDINTYLN (SEQ ID NO: 65); an HVR-L2 comprising the sequence of YTSRLHS (SEQ ID NO: 16); and an HVR-L3 comprising the sequence of QQGNTLPWT (SEQ ID NO: 20).

[0185] In some embodiments, the light chain variable region comprises HVR-L1, HVR-L2, and HVR-L3 of antibody S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.2, and any combination thereof (as shown in Tables 7A to 7C).

[0186] In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable region, wherein the light chain variable region comprises one or more of the following: (a) HVR-L1 comprising a light chain variable region that is identical to antibody S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8. 16. S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7A B-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8 .44.2, S7AB-H8.45.1 or S7AB-H8.45.2 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the HVR-L1 amino acid sequence of antibody S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7. S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7A B-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H 8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.4 1. S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7 an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to an HVR-L2 amino acid sequence of S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, or S7AB-H8.45.2; and ( c) HVR-L3, said HVR-L3 comprising antibodies S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB -H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21. S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S 7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H 8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29 .1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2 has an HVR-L3 amino acid sequence of at least 85 %, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to an antibody, and the antibody is not an antibody comprising a light chain variable region comprising HVR-L1 comprising the sequence of RASQDINTYLN (SEQ ID NO: 65); HVR-L2 comprising the sequence of YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising the sequence of QQGNTLPWT (SEQ ID NO: 20).

[0187] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise HVR-L1 comprising the amino acid sequence RGSQDINTYLN (SEQ ID NO: 11); HVR-L2 comprising the amino acid sequence YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising the amino acid sequence QQGNILPWT (SEQ ID NO: 23).

[0188] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region comprising one or more (e.g., one or more, two or more, or all three) HVRs selected from HVR-H1, HVR-H2, and HVR-H3 (as shown in Tables 6A-6C); and a light chain variable region comprising one or more (e.g., one or more, two or more, or all three) HVRs selected from HVR-L1, HVR-L2, and HVR-L3 (as shown in Tables 7A-7C). In some embodiments, the heavy chain variable region comprises HVR-H1, HVR-H2, and HVR-H3 (as shown in Tables 6A-6C), and the light chain variable region comprises HVR-L1, HVR-L2, and HVR-L3 (as shown in Tables 7A-7C).

[0189] In some embodiments, the heavy chain variable region comprises HVR-H1 according to Formula I, HVR-H2 according to Formula II, and HVR-H3 comprising the sequence of DYSDYYFDY (SEQ ID NO: 10), and the light chain variable region comprises HVR-L1 according to Formula III, HVR-L2 comprising the sequence of YTSRLHS (SEQ ID NO: 16), and HVR-L3 according to Formula IV. In some embodiments, the heavy chain variable region comprises HVR-H1 comprising a sequence selected from the group consisting of SEQ ID NOs: 1-5, HVR-H2 comprising a sequence selected from the group consisting of SEQ ID NOs: 7-8, and HVR-H3 comprising a sequence of SEQ ID NO: 10, and the light chain variable region comprises HVR-L1 comprising a sequence selected from the group consisting of SEQ ID NOs: 11-14, HVR-L2 comprising a sequence of SEQ ID NO: 16, and HVR-L3 comprising a sequence selected from the group consisting of SEQ ID NOs: 17-23. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region comprising antibodies S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11 , S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7A B-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8. 26. S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S 7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB- H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8 .10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.2, and any combination thereof (as shown in Tables 6A to 6C); and a light chain variable region comprising antibody S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26 B-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8 .17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.2 7. S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37 , S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2 , S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, S7AB-H8.45.2, and HVR-L1, HVR-L2, and HVR-L3 of any combination thereof (as shown in Tables 7A to 7C).

[0190] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region comprising HVR-H1, HVR-H2, and HVR-H3; and a light chain variable region comprising HVR-L1, HVR-L2, and HVR-L3, wherein the antibody comprises antibodies S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10 , S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8. 20. S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8 .30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB- H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10. 2. HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2 and HVR-L3 of S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2 (as shown in Tables 6A to 6C and 7A to 6C).

[0191] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises one or more of the following: (a) HVR-H1 comprising the same HVR-H1 as antibodies S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8. B-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8 .27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10 .2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB- H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the HVR-H1 amino acid sequence of antibody S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H87. S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7A B-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H 8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.4 1. S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7 an amino acid sequence having at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to an HVR-H2 amino acid sequence of S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1, or S7AB-H8.45.2; and ( c) HVR-H3, said HVR-H3 comprising antibodies S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB -H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21. S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7A The HVR-H3 amino acid sequence of S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2 has at least 85%, at least 86% , at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable region; and wherein the light chain variable region comprises one or more of the following: (a) HVR-L1 comprising an amino acid sequence that is at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable region; and wherein the light chain variable region comprises one or more of the following: (a) HVR-L1 comprising an amino acid sequence that is at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable region; 7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB -H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33. S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1 , S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2; and (b) an HVR-L2 comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the HVR-L1 amino acid sequence of antibody S7AB-H8, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2; , S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13 , S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7A B-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8 .36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2. The HVR-L2 amino acid sequence of S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2 has at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, or more. and (c) an HVR-L3 comprising an amino acid sequence that is at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to antibody S7AB-H8, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, 6. S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S 7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB- H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7A B-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2. an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the HVR-L3 amino acid sequence of S7AB-H8.45.1 or S7AB-H8.45.2, and the antibody is not an antibody comprising a light chain variable region comprising an HVR-L1 comprising the sequence of RASQDINTYLN (SEQ ID NO: 65); an HVR-L2 comprising the sequence of YTSRLHS (SEQ ID NO: 16); and an HVR-L3 comprising the sequence of QQGNTLPWT (SEQ ID NO: 20).

[0192] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise (a) HVR-H1 comprising the amino acid sequence GYAFTMAWMN (SEQ ID NO: 2); HVR-H2 comprising the amino acid sequence RIFPGYGHTN (SEQ ID NO: 8); HVR-H3 comprising the amino acid sequence DYSDYYFDY (SEQ ID NO: 10); HVR-L1 comprising the amino acid sequence RGSQDINTYLN (SEQ ID NO: 11); HVR-L2 comprising the amino acid sequence YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising the amino acid sequence QQGNLLPWT (SEQ ID NO: 17); (b) HVR-H1 comprising the amino acid sequence GYAFTGYWMN (SEQ ID NO: 2); NO:3); HVR-H2, said HVR-H2 comprising the amino acid sequence of RIFPGLGHTN (SEQ ID NO:7); HVR-H3, said HVR-H3 comprising the amino acid sequence of DYSDYYFDY (SEQ ID NO:10); HVR-L1, said HVR-L1 comprising the amino acid sequence of RGSQDTNTYLN (SEQ ID NO:12); HVR-L2, said HVR-L2 comprising the amino acid sequence of YTSRLHS (SEQ ID NO:16); and HVR-L3, said HVR-L3 comprising the amino acid sequence of QQGNTLPWT (SEQ ID NO:20); (c) HVR-H1, said HVR-H1 comprising the amino acid sequence of GYAFTGYWMN (SEQ ID NO:3); HVR-H2, said HVR-H2 comprising the amino acid sequence of RIFPGLGHTN (SEQ ID NO:7); HVR-H3, said HVR-H3 comprising the amino acid sequence of DYSDYYFDY (SEQ ID NO:10); NO:10); HVR-L1 comprising the amino acid sequence of RGSQDINTYLN (SEQ ID NO:11); HVR-L2 comprising the amino acid sequence of YTSRLHS (SEQ ID NO:16); and HVR-L3 comprising the amino acid sequence of QQGNILPWT (SEQ ID NO:23); or (d) HVR-H1 comprising the amino acid sequence of GYAFTAAWMN (SEQ ID NO:4); and HVR-H2 comprising the amino acid sequence of RIFPGLGHTN (SEQ ID NO:7);HVR-H3, comprising the amino acid sequence of DYSDYYFDY (SEQ ID NO: 10); HVR-L1, comprising the amino acid sequence of RGSQDINTYLN (SEQ ID NO: 11); HVR-L2, comprising the amino acid sequence of YTSRLHS (SEQ ID NO: 16); and HVR-L3, comprising the amino acid sequence of QQGNILPWT (SEQ ID NO: 23).

[0193] In a specific embodiment, an anti-Siglec-7 antibody of the present disclosure comprises HVR-H1 comprising the amino acid sequence GYAFTAAWMN (SEQ ID NO:4); HVR-H2 comprising the amino acid sequence RIFPGLGHTN (SEQ ID NO:7); HVR-H3 comprising the amino acid sequence DYSDYYFDY (SEQ ID NO:10); HVR-L1 comprising the amino acid sequence RGSQDINTYLN (SEQ ID NO:11); HVR-L2 comprising the amino acid sequence YTSRLHS (SEQ ID NO:16); and HVR-L3 comprising the amino acid sequence QQGNILPWT (SEQ ID NO:23).

[0194] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 36-48. In some embodiments, the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 43. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise antibodies S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4 7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8 .18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S 7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H 8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1 , S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2 (as shown in Table 10).

[0195] In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence GYAFTAAWMN (SEQ ID NO: 4); HVR-H2 comprising the amino acid sequence RIFPGLGHTN (SEQ ID NO: 7); and HVR-H3 comprising the amino acid sequence DYSDYYFDY (SEQ ID NO: 10).

[0196] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable region comprising an amino acid sequence selected from SEQ ID NOs: 49-60. In some embodiments, the light chain variable region comprises an amino acid sequence selected from SEQ ID NOs: 60. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise antibodies S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8 7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8 .18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S 7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H 8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1 , S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2 (as shown in Table 11).

[0197] In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable region comprising HVR-L1 comprising the amino acid sequence RGSQDINTYLN (SEQ ID NO: 11); HVR-L2 comprising the amino acid sequence YTSRLHS (SEQ ID NO: 16); and HVR-L3 comprising the amino acid sequence QQGNILPWT (SEQ ID NO: 23).

[0198] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 36-48 and / or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 49-60. In some embodiments, the antibodies comprise a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 41, 42, and 43 and / or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 52, 55, and 60. In some embodiments, the antibody comprises: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:41 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:52; a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:55; a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:60; or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:43 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:60.

[0199] In one aspect, the anti-Siglec-7 antibody of the present disclosure binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 36-48; and / or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 49-60. In some embodiments, the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 41, 42, and 43; and the light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 52, 55, and 60. In some embodiments, (a) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:41, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:52; (b) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:42, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:55; (c) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:42, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:60; or (d) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:43, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:60.

[0200] In one aspect, the anti-Siglec-7 antibody of the present disclosure binds to a Siglec-7 protein, wherein the antibody comprises (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 41 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 52; (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55; (c) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 60; or (d) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 43 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 60.

[0201] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region having the amino acid sequence of SEQ ID NO: 43; and a light chain variable region having the amino acid sequence of SEQ ID NO: 60.

[0202] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise the heavy chain variable regions of antibodies S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S7AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2 (as shown in Table 10), and antibodies S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6、S7AB-H8.7、S7AB-H8.8、S7AB-H8.9、S7AB-H8.10、S7AB-H8.11、S7AB-H8.12、S7AB-H8.13、S7AB-H8.14、S7AB-H8.15、S7AB-H8.16、S7AB-H8.17、S7AB-H8.18、S7AB-H8.19、S7AB-H8.20、S7AB-H8.2 1、S7AB-H8.22、S7AB-H8.23、S7AB-H8.24、S7AB-H8.25、S7AB-H8.26、S7AB-H8.27、S7AB-H8.28、S7AB-H8.29、S7AB-H8.30、S7AB-H8.31、S7AB-H8.32、S7AB-H8.33、S7AB-H8.34、S7AB-H8.35、S7AB-H 8.36、S7AB-H8.37、S7AB-H8.38、S7AB-H8.39、S7AB-H8.40、S7AB-H8.41、S7AB-H8.42、S7AB-H8.43、S7AB-H8.44、S7AB-H8.45、S7AB-H8.9.1、S7AB-H8.9.2、S7AB-H8.10.1、S7AB-H8.10.2、S7AB-H8. 29.1、S7AB-H8.29.2、S7AB-H8.30.1、S7AB-H8.30.2、S7AB-H8.34.1、S7AB-H8.34.2、S7AB-H8.35. 1. S7AB-H8.35.2.

[0203] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 43, and 44. In some embodiments, the antibodies comprise a heavy chain variable region of S7AB-H8.1, S7AB-H8.2, S7AB-H8.11, S7AB-H8.13, S7AB-H8.18, S7AB-H8.20, S7AB-H8.35, S7AB-H8.43, or S7AB-H8.44 (as shown in Table 10). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 52, 54, 55, 58, and 60. In some embodiments, the antibody comprises a light chain variable region of S7AB-H8.1, S7AB-H8.2, S7AB-H8.11, S7AB-H8.13, S7AB-H8.18, S7AB-H8.20, S7AB-H8.35, S7AB-H8.43, or S7AB-H8.44 (as shown in Table 11). In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 43, and 44; and / or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 52, 54, 55, 58, and 60. In some embodiments, the antibody comprises the heavy chain variable region of S7AB-H8.1, S7AB-H8.2, S7AB-H8.11, S7AB-H8.13, S7AB-H8.18, S7AB-H8.20, S7AB-H8.35, S7AB-H8.43, or S7AB-H8.44 (as shown in Table 10), and the light chain variable region of antibody S7AB-H8.1, S7AB-H8.2, S7AB-H8.11, S7AB-H8.13, S7AB-H8.18, S7AB-H8.20, S7AB-H8.35, S7AB-H8.43, or S7AB-H8.44 (as shown in Table 11).

[0204] Any of the antibodies of the present disclosure can be produced by a cell line. In some embodiments, the cell line is a mammalian cell line. In certain embodiments, the cell line is a hybridoma cell line. In other embodiments, the cell line can be a yeast cell line. Any cell line known in the art to be suitable for antibody production can be used to produce the antibodies of the present disclosure. Exemplary cell lines for antibody production are described throughout this disclosure.

[0205] In some embodiments, the anti-Siglec-7 antibody is an anti-Siglec-7 monoclonal antibody comprising a heavy chain variable region and a light chain variable region of an antibody selected from: S7AB-H1, S7AB-H2, S7AB-H3, S7AB-H4, S7AB-H5, S7AB-H6, S7AB-H7, S7AB-H8, S7AB-H9, S7AB-H10, S7AB-H11, S7AB-H12, S7AB-H8.1, S7AB-H8.2, S7AB-H8.3, S7AB-H8.4, S7AB-H8.5, S7AB-H8.6, S7AB-H8.7, S7AB-H8.8, S7AB-H8.9, S7AB-H8.10, S7AB-H8.11, S7AB-H8.12, S7AB-H8.13, S7AB-H8.14, S7AB-H8.15, S7AB-H8.16, S7AB-H8.17, S7AB-H8.18, S7AB-H8.19, S7AB-H8.20, S7AB-H8.21, S7AB-H8.22, S7AB-H8.23, S7AB-H8.24, S7AB-H8.25, S7AB-H8.26, S7AB-H8.27, S7AB-H8.28, S7AB-H8.29, S7AB-H8.30, S7AB-H8.31, S7AB-H8.32, S7AB-H8.33, S7AB-H8.34, S7AB-H8.35, S7AB-H8.36, S7AB-H8.37, S7AB-H8.38, S7AB-H8.39, S7AB-H8.40, S7AB-H8.41, S7AB-H8.42, S7AB-H8.43, S7AB-H8.44, S7AB-H8.45, S7AB-H8.9.1, S7AB-H8.9.2, S7AB-H8.10.1, S7AB-H8.10.2, S�AB-H8.29.1, S7AB-H8.29.2, S7AB-H8.30.1, S7AB-H8.30.2, S7AB-H8.34.1, S7AB-H8.34.2, S7AB-H8.35.1, S7AB-H8.35.2, S7AB-H8.44.1, S7AB-H8.44.2, S7AB-H8.45.1 or S7AB-H8.45.2.

[0206] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.1 or the amino acid sequence of SEQ ID NO: 40; and / or the light chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.1 or the amino acid sequence of SEQ ID NO: The amino acid sequence of NO:52 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.1 or to the amino acid sequence of SEQ ID NO:40, wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2, and HVR-H3 amino acid sequences of antibody S7AB-H8.1. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.1 or to the amino acid sequence of SEQ ID NO: 52, wherein the light chain variable domain comprises the HVR-L1, HVR-L2, and HVR-L3 amino acid sequences of antibody S7AB-H8.1.In some embodiments, the anti-Siglec-7 antibody comprises a heavy chain variable domain (VH) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.1 or the amino acid sequence of SEQ ID NO: 40, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibody comprising the sequence retains the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.1 or the amino acid sequence of SEQ ID NO: 40. In certain embodiments, in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.1 or the amino acid sequence of SEQ ID NO: 40, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VH sequence of antibody S7AB-H8.1 or SEQ ID NO: 40, including post-translational modifications of the sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from the following: (a) the HVR-H1 amino acid sequence of antibody S7AB-H8.1, (b) the HVR-H2 amino acid sequence of antibody S7AB-H8.1, and (c) the HVR-H3 amino acid sequence of antibody S7AB-H8.1. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain (VL) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.1 or the amino acid sequence of SEQ ID NO: 52, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibodies comprising the sequence retain the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the light chain variable domain amino acid sequence of antibody S7AB-H8.1 or the amino acid sequence of SEQ ID NO: 52.In certain embodiments, in the light chain variable domain amino acid sequence of antibody S7AB-H8.1 or the amino acid sequence of SEQ ID NO: 52, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VL sequence of antibody S7AB-H8.1 or SEQ ID NO: 52, including post-translational modifications of the sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from the following: (a) the HVR-L1 amino acid sequence of antibody S7AB-H8.1, (b) the HVR-L2 amino acid sequence of antibody S7AB-H8.1, and (c) the HVR-L3 amino acid sequence of antibody S7AB-H8.1.

[0207] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.2 or the amino acid sequence of SEQ ID NO: 41; and / or the light chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.2 or the amino acid sequence of SEQ ID NO: The amino acid sequence of NO:52 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.2 or to the amino acid sequence of SEQ ID NO:41, wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2, and HVR-H3 amino acid sequences of antibody S7AB-H8.2. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.2 or with the amino acid sequence of SEQ ID NO: 52, wherein the light chain variable domain comprises the HVR-L1, HVR-L2, and HVR-L3 amino acid sequences of antibody S7AB-H8.2.In some embodiments, the anti-Siglec-7 antibody comprises a heavy chain variable domain (VH) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.2 or the amino acid sequence of SEQ ID NO: 41, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibody comprising the sequence retains the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.2 or the amino acid sequence of SEQ ID NO: 41. In certain embodiments, in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.2 or the amino acid sequence of SEQ ID NO: 41, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VH sequence of antibody S7AB-H8.2 or SEQ ID NO: 41, including post-translational modifications of the sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from the following: (a) the HVR-H1 amino acid sequence of antibody S7AB-H8.2, (b) the HVR-H2 amino acid sequence of antibody S7AB-H8.2, and (c) the HVR-H3 amino acid sequence of antibody S7AB-H8.2. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain (VL) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.2 or the amino acid sequence of SEQ ID NO: 52, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibodies comprising the sequence retain the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the light chain variable domain amino acid sequence of antibody S7AB-H8.2 or the amino acid sequence of SEQ ID NO: 52.In certain embodiments, in the light chain variable domain amino acid sequence of antibody S7AB-H8.2 or the amino acid sequence of SEQ ID NO: 52, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VL sequence of antibody S7AB-H8.2 or SEQ ID NO: 52, including post-translational modifications of the sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from the following: (a) the HVR-L1 amino acid sequence of antibody S7AB-H8.2, (b) the HVR-L2 amino acid sequence of antibody S7AB-H8.2, and (c) the HVR-L3 amino acid sequence of antibody S7AB-H8.2.

[0208] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.11 or the amino acid sequence of SEQ ID NO: 40; and / or the light chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.11 or the amino acid sequence of SEQ ID NO: The amino acid sequence of NO:54 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.11 or to the amino acid sequence of SEQ ID NO:40, wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2 and HVR-H3 amino acid sequences of antibody S7AB-H8.11. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.11 or with the amino acid sequence of SEQ ID NO: 54, wherein the light chain variable domain comprises the HVR-L1, HVR-L2 and HVR-L3 amino acid sequences of antibody S7AB-H8.11.In some embodiments, the anti-Siglec-7 antibody comprises a heavy chain variable domain (VH) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.11 or the amino acid sequence of SEQ ID NO: 40, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibody comprising the sequence retains the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.11 or the amino acid sequence of SEQ ID NO: 40. In certain embodiments, in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.11 or the amino acid sequence of SEQ ID NO: 40, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VH sequence of antibody S7AB-H8.11 or SEQ ID NO: 40, including post-translational modifications of the sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from the following: (a) the HVR-H1 amino acid sequence of antibody S7AB-H8.11, (b) the HVR-H2 amino acid sequence of antibody S7AB-H8.11, and (c) the HVR-H3 amino acid sequence of antibody S7AB-H8.11. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain (VL) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.11 or the amino acid sequence of SEQ ID NO: 54, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibodies comprising the sequence retain the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the light chain variable domain amino acid sequence of antibody S7AB-H8.11 or the amino acid sequence of SEQ ID NO: 54.In certain embodiments, in the light chain variable domain amino acid sequence of antibody S7AB-H8.11 or the amino acid sequence of SEQ ID NO: 54, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VL sequence of antibody S7AB-H8.11 or SEQ ID NO: 54, including post-translational modifications of the sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from the following: (a) the HVR-L1 amino acid sequence of antibody S7AB-H8.11, (b) the HVR-L2 amino acid sequence of antibody S7AB-H8.11, and (c) the HVR-L3 amino acid sequence of antibody S7AB-H8.11.

[0209] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.13 or the amino acid sequence of SEQ ID NO: 42; and / or the light chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.13 or the amino acid sequence of SEQ ID NO: The amino acid sequence of NO:54 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.13 or with the amino acid sequence of SEQ ID NO:42, wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2 and HVR-H3 amino acid sequences of antibody S7AB-H8.13. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.13 or with the amino acid sequence of SEQ ID NO: 54, wherein the light chain variable domain comprises the HVR-L1, HVR-L2 and HVR-L3 amino acid sequences of antibody S7AB-H8.13.In some embodiments, the anti-Siglec-7 antibody comprises a heavy chain variable domain (VH) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.13 or the amino acid sequence of SEQ ID NO: 42, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibody comprising the sequence retains the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.13 or the amino acid sequence of SEQ ID NO: 42. In certain embodiments, in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.13 or the amino acid sequence of SEQ ID NO: 42, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VH sequence of antibody S7AB-H8.13 or SEQ ID NO: 42, including post-translational modifications of the sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from the following: (a) the HVR-H1 amino acid sequence of antibody S7AB-H8.13, (b) the HVR-H2 amino acid sequence of antibody S7AB-H8.13, and (c) the HVR-H3 amino acid sequence of antibody S7AB-H8.13. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain (VL) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.13 or the amino acid sequence of SEQ ID NO: 54, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibodies comprising the sequence retain the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the light chain variable domain amino acid sequence of antibody S7AB-H8.13 or the amino acid sequence of SEQ ID NO: 54.In certain embodiments, in the light chain variable domain amino acid sequence of antibody S7AB-H8.13 or the amino acid sequence of SEQ ID NO: 54, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VL sequence of antibody S7AB-H8.13 or SEQ ID NO: 54, including post-translational modifications of the sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from the following: (a) the HVR-L1 amino acid sequence of antibody S7AB-H8.13, (b) the HVR-L2 amino acid sequence of antibody S7AB-H8.13, and (c) the HVR-L3 amino acid sequence of antibody S7AB-H8.13.

[0210] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.18 or the amino acid sequence of SEQ ID NO: 42; and / or the light chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.18 or the amino acid sequence of SEQ ID NO: The amino acid sequence of NO:55 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.18 or with the amino acid sequence of SEQ ID NO:42, wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2 and HVR-H3 amino acid sequences of antibody S7AB-H8.18. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.18 or with the amino acid sequence of SEQ ID NO: 55, wherein the light chain variable domain comprises the HVR-L1, HVR-L2 and HVR-L3 amino acid sequences of antibody S7AB-H8.18.In some embodiments, the anti-Siglec-7 antibody comprises a heavy chain variable domain (VH) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.18 or the amino acid sequence of SEQ ID NO: 42, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibody comprising the sequence retains the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.18 or the amino acid sequence of SEQ ID NO: 42. In certain embodiments, in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.18 or the amino acid sequence of SEQ ID NO: 42, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VH sequence of antibody S7AB-H8.18 or SEQ ID NO: 42, including post-translational modifications of the sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from the following: (a) the HVR-H1 amino acid sequence of antibody S7AB-H8.18, (b) the HVR-H2 amino acid sequence of antibody S7AB-H8.18, and (c) the HVR-H3 amino acid sequence of antibody S7AB-H8.18. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain (VL) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.18 or the amino acid sequence of SEQ ID NO: 55, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibodies comprising the sequence retain the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the light chain variable domain amino acid sequence of antibody S7AB-H8.18 or the amino acid sequence of SEQ ID NO: 55.In certain embodiments, in the light chain variable domain amino acid sequence of antibody S7AB-H8.18 or the amino acid sequence of SEQ ID NO: 55, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VL sequence of antibody S7AB-H8.18 or SEQ ID NO: 55, including post-translational modifications of the sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from the following: (a) the HVR-L1 amino acid sequence of antibody S7AB-H8.18, (b) the HVR-L2 amino acid sequence of antibody S7AB-H8.18, and (c) the HVR-L3 amino acid sequence of antibody S7AB-H8.18.

[0211] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.20 or the amino acid sequence of SEQ ID NO: 44; and / or the light chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.20 or the amino acid sequence of SEQ ID NO: The amino acid sequence of NO:55 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.20 or with the amino acid sequence of SEQ ID NO:44, wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2 and HVR-H3 amino acid sequences of antibody S7AB-H8.20. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.20 or with the amino acid sequence of SEQ ID NO: 55, wherein the light chain variable domain comprises the HVR-L1, HVR-L2 and HVR-L3 amino acid sequences of antibody S7AB-H8.20.In some embodiments, the anti-Siglec-7 antibody comprises a heavy chain variable domain (VH) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.20 or the amino acid sequence of SEQ ID NO: 44, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibody comprising the sequence retains the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.20 or the amino acid sequence of SEQ ID NO: 44. In certain embodiments, in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.20 or the amino acid sequence of SEQ ID NO: 44, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VH sequence of antibody S7AB-H8.20 or SEQ ID NO: 44, including post-translational modifications of the sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from the following: (a) the HVR-H1 amino acid sequence of antibody S7AB-H8.20, (b) the HVR-H2 amino acid sequence of antibody S7AB-H8.20, and (c) the HVR-H3 amino acid sequence of antibody S7AB-H8.20. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain (VL) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.20 or the amino acid sequence of SEQ ID NO: 55, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibodies comprising the sequence retain the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the light chain variable domain amino acid sequence of antibody S7AB-H8.20 or the amino acid sequence of SEQ ID NO: 55.In certain embodiments, in the light chain variable domain amino acid sequence of antibody S7AB-H8.20 or the amino acid sequence of SEQ ID NO: 55, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VL sequence of antibody S7AB-H8.20 or SEQ ID NO: 55, including post-translational modifications of the sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from the following: (a) the HVR-L1 amino acid sequence of antibody S7AB-H8.20, (b) the HVR-L2 amino acid sequence of antibody S7AB-H8.20, and (c) the HVR-L3 amino acid sequence of antibody S7AB-H8.20.

[0212] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.35 or the amino acid sequence of SEQ ID NO: 44; and / or the light chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.35 or the amino acid sequence of SEQ ID NO: The amino acid sequence of NO:58 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.35 or with the amino acid sequence of SEQ ID NO:44, wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2 and HVR-H3 amino acid sequences of antibody S7AB-H8.35. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.35 or with the amino acid sequence of SEQ ID NO: 58, wherein the light chain variable domain comprises the HVR-L1, HVR-L2 and HVR-L3 amino acid sequences of antibody S7AB-H8.35.In some embodiments, the anti-Siglec-7 antibody comprises a heavy chain variable domain (VH) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.35 or the amino acid sequence of SEQ ID NO: 44, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibody comprising the sequence retains the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.35 or the amino acid sequence of SEQ ID NO: 44. In certain embodiments, in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.35 or the amino acid sequence of SEQ ID NO: 44, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VH sequence of antibody S7AB-H8.35 or SEQ ID NO: 44, including post-translational modifications of the sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from the following: (a) the HVR-H1 amino acid sequence of antibody S7AB-H8.35, (b) the HVR-H2 amino acid sequence of antibody S7AB-H8.35, and (c) the HVR-H3 amino acid sequence of antibody S7AB-H8.35. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain (VL) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.35 or the amino acid sequence of SEQ ID NO: 58, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibodies comprising the sequence retain the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the light chain variable domain amino acid sequence of antibody S7AB-H8.35 or the amino acid sequence of SEQ ID NO: 58.In certain embodiments, in the light chain variable domain amino acid sequence of antibody S7AB-H8.35 or the amino acid sequence of SEQ ID NO: 58, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VL sequence of antibody S7AB-H8.35 or SEQ ID NO: 58, including post-translational modifications of the sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from the following: (a) the HVR-L1 amino acid sequence of antibody S7AB-H8.35, (b) the HVR-L2 amino acid sequence of antibody S7AB-H8.35, and (c) the HVR-L3 amino acid sequence of antibody S7AB-H8.35.

[0213] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.43 or the amino acid sequence of SEQ ID NO: 42; and / or the light chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.43 or the amino acid sequence of SEQ ID NO: The amino acid sequence of NO:60 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.43 or with the amino acid sequence of SEQ ID NO:42, wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2 and HVR-H3 amino acid sequences of antibody S7AB-H8.43. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.43 or with the amino acid sequence of SEQ ID NO: 60, wherein the light chain variable domain comprises the HVR-L1, HVR-L2 and HVR-L3 amino acid sequences of antibody S7AB-H8.43.In some embodiments, the anti-Siglec-7 antibody comprises a heavy chain variable domain (VH) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.43 or the amino acid sequence of SEQ ID NO: 42, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibody comprising the sequence retains the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.43 or the amino acid sequence of SEQ ID NO: 42. In certain embodiments, in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.43 or the amino acid sequence of SEQ ID NO: 42, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (ie, in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VH sequence of antibody S7AB-H8.43 or SEQ ID NO: 42, including post-translational modifications of the sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from the following: (a) the HVR-H1 amino acid sequence of antibody S7AB-H8.43, (b) the HVR-H2 amino acid sequence of antibody S7AB-H8.43, and (c) the HVR-H3 amino acid sequence of antibody S7AB-H8.43. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain (VL) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.43 or the amino acid sequence of SEQ ID NO: 60, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibodies comprising the sequence retain the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the light chain variable domain amino acid sequence of antibody S7AB-H8.43 or the amino acid sequence of SEQ ID NO: 60.In certain embodiments, in the light chain variable domain amino acid sequence of antibody S7AB-H8.43 or the amino acid sequence of SEQ ID NO: 60, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VL sequence of antibody S7AB-H8.43 or SEQ ID NO: 60, including post-translational modifications of the sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from the following: (a) the HVR-L1 amino acid sequence of antibody S7AB-H8.43, (b) the HVR-L2 amino acid sequence of antibody S7AB-H8.43, and (c) the HVR-L3 amino acid sequence of antibody S7AB-H8.43.

[0214] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain and a heavy chain variable domain, wherein the heavy chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.44 or the amino acid sequence of SEQ ID NO: 43; and / or the light chain variable domain comprises an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.44 or the amino acid sequence of SEQ ID NO: The amino acid sequence of NO:60 has an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a heavy chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the amino acid sequence of the heavy chain variable domain of antibody S7AB-H8.44 or with the amino acid sequence of SEQ ID NO:43, wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2 and HVR-H3 amino acid sequences of antibody S7AB-H8.44. In some embodiments, an anti-Siglec-7 antibody of the present disclosure comprises a light chain variable domain comprising an amino acid sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.44 or with the amino acid sequence of SEQ ID NO: 60, wherein the light chain variable domain comprises the HVR-L1, HVR-L2 and HVR-L3 amino acid sequences of antibody S7AB-H8.44.In some embodiments, the anti-Siglec-7 antibody comprises a heavy chain variable domain (VH) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the heavy chain variable domain amino acid sequence of antibody S7AB-H8.44 or the amino acid sequence of SEQ ID NO: 43, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibody comprising the sequence retains the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.44 or the amino acid sequence of SEQ ID NO: 43. In certain embodiments, in the heavy chain variable domain amino acid sequence of antibody S7AB-H8.44 or the amino acid sequence of SEQ ID NO: 43, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (ie, in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VH sequence of antibody S7AB-H8.44 or SEQ ID NO: 43, including post-translational modifications of the sequence. In a specific embodiment, the VH comprises one, two or three HVRs selected from the following: (a) the HVR-H1 amino acid sequence of antibody S7AB-H8.44, (b) the HVR-H2 amino acid sequence of antibody S7AB-H8.44, and (c) the HVR-H3 amino acid sequence of antibody S7AB-H8.44. In some embodiments, the anti-Siglec-7 antibodies of the present disclosure comprise a light chain variable domain (VL) sequence that is at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identical to the light chain variable domain amino acid sequence of antibody S7AB-H8.44 or the amino acid sequence of SEQ ID NO: 60, and contains substitutions (e.g., conservative substitutions, insertions or deletions relative to the reference sequence), but the anti-Siglec-7 antibodies comprising the sequence retain the ability to bind to Siglec-7. In certain embodiments, a total of 1 to 10 amino acids have been substituted, inserted and / or deleted in the light chain variable domain amino acid sequence of antibody S7AB-H8.44 or the amino acid sequence of SEQ ID NO: 60.In certain embodiments, in the light chain variable domain amino acid sequence of antibody S7AB-H8.44 or the amino acid sequence of SEQ ID NO: 60, a total of 1 to 5 amino acids have been substituted, inserted and / or deleted. In certain embodiments, the substitution, insertion or deletion occurs in a region other than HVR (i.e., in the FR region). In some embodiments, the substitution, insertion or deletion occurs in the FR region. Optionally, the anti-Siglec-7 antibody comprises the VL sequence of antibody S7AB-H8.44 or SEQ ID NO: 60, including post-translational modifications of the sequence. In a specific embodiment, the VL comprises one, two or three HVRs selected from the following: (a) the HVR-L1 amino acid sequence of antibody S7AB-H8.44, (b) the HVR-L2 amino acid sequence of antibody S7AB-H8.44, and (c) the HVR-L3 amino acid sequence of antibody S7AB-H8.44.

[0215] In some embodiments, the anti-Siglec-7 antibody is the anti-Siglec-7 monoclonal antibody S7AB-H8. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody that binds to substantially the same Siglec-7 epitope as S7AB-H8. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the heavy chain variable region of the monoclonal antibody S7AB-H8. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the light chain variable region of the monoclonal antibody S7AB-H8. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the heavy chain variable region and the light chain variable region of the monoclonal antibody S7AB-H8.

[0216] In some embodiments, the anti-Siglec-7 antibody is the anti-Siglec-7 monoclonal antibody S7AB-H9. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody that binds to substantially the same Siglec-7 epitope as S7AB-H9. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the heavy chain variable region of the monoclonal antibody S7AB-H9. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the light chain variable region of the monoclonal antibody S7AB-H9. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the heavy chain variable region and the light chain variable region of the monoclonal antibody S7AB-H9.

[0217] In some embodiments, the anti-Siglec-7 antibody is the anti-Siglec-7 monoclonal antibody S7AB-H11. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody that binds to substantially the same Siglec-7 epitope as S7AB-H11. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the heavy chain variable region of the monoclonal antibody S7AB-H11. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the light chain variable region of the monoclonal antibody S7AB-H11. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the heavy chain variable region and the light chain variable region of the monoclonal antibody S7AB-H11.

[0218] In some embodiments, the anti-Siglec-7 antibody is the anti-Siglec-7 monoclonal antibody S7AB-H12. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody that binds to substantially the same Siglec-7 epitope as S7AB-H12. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the heavy chain variable region of the monoclonal antibody S7AB-H12. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the light chain variable region of the monoclonal antibody S7AB-H12. In some embodiments, the anti-Siglec-7 antibody is an isolated antibody comprising the heavy chain variable region and the light chain variable region of the monoclonal antibody S7AB-H12.

[0219] In certain embodiments, the anti-Siglec-7 antibody is an antagonist antibody. In certain embodiments, the anti-Siglec-7 antibody is an agonist antibody or an inert antibody. In some embodiments, the anti-Siglec-7 antibody of the present disclosure has an IgG class, an IgM class, or an IgA class. In some embodiments, the anti-Siglec-7 antibody of the present disclosure has an IgG class and has an IgG1, IgG2, IgG3, or IgG4 isotype.

[0220] Additional anti-Siglec-7 antibodies can be identified, screened, and / or characterized by various assays known in the art, such as the physical / chemical properties and / or biological activity of antibodies that specifically bind to the Siglec-7 proteins of the present disclosure.

[0221] Anti-Siglec-7 antibodies capable of binding to Fcγ receptors

[0222] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure retain the ability to bind to Fcγ (Fcγ) receptors. In some embodiments, when such antibodies have the correct epitope specificity compatible with receptor activation, such antibodies may have characteristics that enable them to cluster and transiently stimulate, for example, Siglec-7 receptors. In some embodiments, such antibodies can then act as long-term inhibitors of one or more activities of Siglec-7 expression and / or Siglec-7 protein by inducing Siglec-7 degradation, Siglec-7 desensitization, Siglec-7 cleavage, Siglec-7 internalization, Siglec-7 shedding, downregulation of Siglec-7 expression, and / or lysosomal degradation of Siglec-7.

[0223] In vivo, the anti-Siglec-7 antibodies of the present disclosure can cluster receptors and transiently activate Siglec-7 through any one or more of a variety of potential mechanisms. Some isotypes of human antibodies, such as IgG2, have an intrinsic ability to cluster receptors or retain receptors in a clustered configuration due to their unique structure, thereby transiently activating receptors such as Siglec-7 without binding to Fc receptors (e.g., White et al., (2015) Cancer Cell 27, 138–148).

[0224] In some embodiments, other antibodies can cluster receptors (e.g., Siglec-7) by binding to Fcγ receptors on neighboring cells. In some embodiments, binding of the constant IgG Fc region of an antibody to an Fcγ receptor can result in aggregation of the antibody, and the antibodies can in turn aggregate the receptors to which they bind via their variable regions (Chu et al. (2008) Mol Immunol, 45:3926-3933; and Wilson et al. (2011) Cancer Cell 19, 101–113). In some embodiments, binding to inhibitory Fcγ receptors FcγR (FcγRIIB) that do not induce cytokine secretion, oxidative burst, increased phagocytosis, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) is a preferred way to cluster antibodies in vivo because binding to FcγRIIB is not associated with adverse immune response effects.

[0225] There are other mechanisms by which the anti-Siglec-7 antibodies of the present disclosure can cluster receptors. For example, as described above, cross-linked antibody fragments (e.g., Fab fragments) can be used to cluster receptors (e.g., Siglec-7) in a manner similar to antibodies with Fc regions that bind to Fcγ receptors. In some embodiments, if the cross-linked antibody fragments (e.g., Fab fragments) induce receptor clustering on the cell surface and bind to the appropriate epitope on the target (e.g., Siglec-7), the antibody fragments can transiently act as agonist antibodies.

[0226] Thus, in some embodiments, antibodies of the present disclosure that bind to Siglec-7 proteins may include antibodies that bind to Siglec-7 and transiently activate one or more Siglec-7 activities due to their epitope specificity before they, for example, reduce the cellular level of Siglec-7, inhibit one or more Siglec-7 activities, and / or inhibit the interaction (e.g., binding) between Siglec-7 and one or more Siglec-7 ligands. In some embodiments, such antibodies can bind to the ligand binding site on Siglec-7 and transiently mimic the effects of the natural ligand, or stimulate target antigen transduction signals by binding to one or more domains that are not ligand binding sites. In some embodiments, such antibodies do not interfere with ligand binding. In some embodiments, regardless of whether the antibody binds to the ligand binding site on Siglec-7, the antibody can subsequently act as a long-term inhibitor of Siglec-7 expression and / or one or more activities of the Siglec-7 protein by inducing Siglec-7 degradation, Siglec-7 desensitization, Siglec-7 cleavage, Siglec-7 internalization, Siglec-7 shedding, downregulation of Siglec-7 expression, and / or lysosomal degradation of Siglec-7.

[0227] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure are antibodies that transiently induce one or more activities of Siglec-7 proteins. Any suitable technique or assay known in the art and disclosed herein can be used to test the ability of the anti-Siglec-7 antibodies of the present disclosure to transiently induce one or more activities of Siglec-7 proteins. Regardless of the activity transiently induced by such antibodies, such antibodies can subsequently act as long-term inhibitors of one or more activities of Siglec-7 expression and / or Siglec-7 proteins by inducing Siglec-7 degradation, Siglec-7 desensitization, Siglec-7 cleavage, Siglec-7 internalization, Siglec-7 shedding, downregulation of Siglec-7 expression, and / or lysosomal degradation of Siglec-7. In some embodiments, the Siglec-7 antibody transiently induces one or more activities of the Siglec-7 protein independent of binding to an Fc receptor.

[0228] Exemplary antibody Fc isotypes and modifications are provided below in Table B. In some embodiments, an anti-Siglec-7 antibody of the disclosure capable of binding to an Fcγ receptor has an Fc isotype listed in Table B below.

[0229] Table B: Exemplary anti-Siglec-7 antibody Fc isotypes capable of binding to Fcγ receptors

[0230]

[0231]

[0232] In addition to the isotypes described in Table C, and without wishing to be bound by theory, it is believed that antibodies with the human IgG1 or IgG3 isotype and mutants thereof that bind to Fcγ receptors I, IIA, IIC, IIIA, IIIB in humans and / or Fcγ receptors I, III and IV in mice (e.g., Strohl (2009) Current Opinion in Biotechnology 2009, 20:685–691) may also act as transient agonist antibodies.

[0233] In some embodiments, the Fc γ receptor binding antibodies have IgG classes, IgM classes or IgA classes. In some embodiments, the Fc γ receptor binding antibodies have IgG1, IgG2, IgG3 or IgG4 isotypes. In some embodiments, the antibody is included in the Fc region at one or more (for example, one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, 10 or more, 11 or more, 12 or more or all 13) amino acid replacements at the residue position of the group selected from the following composition: C127S, L234A, L234F, L235A, L235E, S267E, N297A, K322A, L328F, A330S, P331S, E345R, E430G, S440Y and any combination thereof (residue position is according to EU or Kabat numbering). In some embodiments, the Fc region comprises an amino acid substitution at position P331S, wherein the numbering of residue positions is according to EU numbering. In some embodiments, the Fc region comprises an amino acid substitution at position E430G. In some embodiments, the Fc region comprises an amino acid substitution at position L234A, L235A, and P331S. In some embodiments, the Fc region comprises an amino acid substitution at position N297A. In some embodiments, the Fc region comprises an amino acid substitution at position K322A and E430G. In some embodiments, the Fc region comprises an amino acid substitution at position P331S and E430G. In some embodiments, the Fc region comprises an amino acid substitution at position A330S, P331S, and E430G. In some embodiments, the Fc region comprises an amino acid substitution at position K322A, A330S, and P331S. In some embodiments, the Fc region comprises an amino acid substitution at position K322A, P331S, and E430G. In some embodiments, the Fc region comprises amino acid substitutions at positions A330S, P331S, and E430G. In some embodiments, the Fc region comprises amino acid substitutions at positions S267E and L328F. In some embodiments, the Fc region comprises amino acid substitutions at position C127S. In some embodiments, the Fc region comprises amino acid substitutions at positions E345R, E430G, and S440Y. In some embodiments, the Siglec-7 antibodies of the present disclosure have an IgG1 isotype and comprise an S267E amino acid substitution at residue position 267 and an L328F amino acid substitution at residue position 328, wherein the numbering of the residue positions is according to EU numbering.

[0234] In certain embodiments, the Fcγ receptor binding antibody has an IgG2 isotype. In some embodiments, the Fcγ receptor binding antibody contains a human IgG2 constant region. In some embodiments, the human IgG2 constant region includes an Fc region. In some embodiments, the Fcγ receptor binding antibody binds to an inhibitory Fc receptor. In certain embodiments, the inhibitory Fc receptor is an inhibitory Fc-γ receptor IIB (FcγIIB). In some embodiments, the Fc region contains one or more modifications. For example, in some embodiments, the Fc region contains one or more amino acid substitutions (e.g., relative to a wild-type Fc region of the same isotype). In some embodiments, the one or more amino acid substitutions are selected from V234A (Alegre et al., (1994) Transplantation 57:1537-1543.31; Xu et al., (2000) Cell Immunol, 200:16-26), G237A (Cole et al. (1999) Transplantation, 68:563-571), H268Q, V309L, A330S, P331S (US2007 / 0148167; Armour et al. (1999) Eur J Immunol 29:2613-2624; Armour et al. (2000) The Haematology Journal 1(Suppl. 1):27; Armour et al. (2000) The Haematology Journal 1(Suppl. 1):27), C232S and / or C233S (White et al. (2015) Cancer Cell 27, 138–148), S267E, L328F (Chu et al., (2008) Mol Immunol, 45:3926-3933), M252Y, S254T and / or T256E, wherein the amino acid positions are according to the EU or Kabat numbering convention.

[0235] In some embodiments, the Fcγ receptor binding antibody is of the IgG2 isotype having a heavy chain constant domain comprising a C127S amino acid substitution, wherein amino acid positions are according to the EU or Kabat numbering convention (White et al., (2015) Cancer Cell 27, 138-148; Lightle et al., (2010) PROTEIN SCIENCE 19:753-762; and WO2008079246).

[0236] In some embodiments, the Fcγ receptor binding antibody is of the IgG2 isotype having a kappa light chain constant domain comprising a C214S amino acid substitution, wherein amino acid positions are according to the EU or Kabat numbering convention (White et al., (2015) Cancer Cell 27, 138-148; Lightle et al., (2010) PROTEIN SCIENCE 19:753-762; and WO2008079246).

[0237] In certain embodiments, the Fcγ receptor binding antibody has an IgG1 isotype. In some embodiments, the Fcγ receptor binding antibody contains a mouse IgG1 constant region. In some embodiments, the Fcγ receptor binding antibody contains a human IgG1 constant region. In some embodiments, the human IgG1 constant region includes an Fc region. In some embodiments, the Fcγ receptor binding antibody binds to an inhibitory Fc receptor. In certain embodiments, the inhibitory Fc receptor is an inhibitory Fc-γ receptor IIB (FcγIIB). In some embodiments, the Fc region contains one or more modifications. For example, in some embodiments, the Fc region contains one or more amino acid substitutions (e.g., relative to a wild-type Fc region of the same isotype). In some embodiments, the one or more amino acid substitutions are selected from N297A (Bolt S et al. (1993) Eur J Immunol 23:403-411), D265A (Shields et al. (2001) RJ Biol. Chem. 276, 6591-6604), D270A, L234A, L235A (Hutchins et al. (1995) Proc Natl Acad Sci USA, 92: 11980-11984; Alegre et al. (1994) Transplantation 57: 1537-1543.31; Xu et al. (2000) Cell Immunol, 200: 16-26), G237A (Alegre et al. (1994) Transplantation 57: 1537-1543.31; Xu et al. (2000) Cell Immunol, 200: 16-26). Immunol, 200: 16-26), P238D, L328E, E233D, G237D, H268D, P271G, A330R, C226S, C229S, E233P, L234V, L234F, L235E (McEarchern et al., (2007) Blood, 109: 1185-1192), P331S (Sazinsky et al., (2008) Proc Natl Acad Sci USA 2008, 105:20167-20172), S267E, L328F, A330L, M252Y, S254T, T256E, N297Q, P238S, P238A, A327Q, A327G, P329A, K322A and / or T394D, wherein the amino acid positions are according to the EU or Kabat numbering convention.

[0238] In some embodiments, the antibody comprises an IgG2 isotype heavy chain constant domain 1 (CH1) and hinge region (White et al., (2015) Cancer Cell 27, 138-148). In certain embodiments, the IgG2 isotype CH1 and hinge region comprise the amino acid sequence of ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF PAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVE CPPCP (SEQ ID NO: 64). In some embodiments, the antibody Fc region comprises an S267E amino acid substitution, an L328F amino acid substitution, or both, and / or an N297A or N297Q amino acid substitution, wherein the amino acid positions are according to EU or Kabat numbering conventions.

[0239] In certain embodiments, the Fcγ receptor binding antibody has an IgG4 isotype. In some embodiments, the Fcγ receptor binding antibody contains a human IgG4 constant region. In some embodiments, the human IgG4 constant region includes an Fc region. In some embodiments, the Fcγ receptor binding antibody binds to an inhibitory Fc receptor. In certain embodiments, the inhibitory Fc receptor is an inhibitory Fc-γ receptor IIB (FcγIIB). In some embodiments, the Fc region contains one or more modifications. For example, in some embodiments, the Fc region contains one or more amino acid substitutions (e.g., relative to a wild-type Fc region of the same isotype). In some embodiments, the one or more amino acid substitutions are selected from L235A, G237A, S228P, L236E (Reddy et al., (2000) J Immunol, 164: 1925-1933), S267E, E318A, L328F, M252Y, S254T and / or T256E, wherein the amino acid positions are according to the EU or Kabat numbering convention.

[0240] In certain embodiments, the Fcγ receptor binding antibody has a hybrid IgG2 / 4 isotype. In some embodiments, the Fcγ receptor binding antibody comprises an amino acid sequence comprising amino acids 118 to 260 of human IgG2 according to EU or Kabat numbering and amino acids 261-447 of human IgG4 according to EU or Kabat numbering (WO 1997 / 11971; WO 2007 / 106585).

[0241] In certain embodiments, the antibody contains a mouse IgG4 constant region (Bartholomaeus, et al. (2014). J. Immunol. 192, 2091-2098).

[0242] In some embodiments, the Fc region further contains one or more additional amino acid substitutions selected from the group consisting of A330L, L234F, L235E, or P331S according to EU or Kabat numbering, and any combination thereof.

[0243] In certain embodiments, the antibody contains one or more amino acid replacements at a residue position selected from C127S, L234A, L234F, L235A, L235E, S267E, K322A, L328F, A330S, P331S, E345R, E430G, S440Y and any combination thereof in the Fc region, wherein the numbering of the residues is according to EU or Kabat numbering. In some embodiments, the Fc region comprises an amino acid replacement at position P331S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region comprises an amino acid replacement at position E430G, L234A, L235A and P331S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region comprises an amino acid replacement at position N297A, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at positions E430G and P331S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at positions E430G and K322A, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at positions E430G, A330S, and P331S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at positions E430G, K322A, A330S, and P331S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at positions E430G, K322A, A330S, and P331S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at positions E430G, K322A, and A330S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at positions E430G, K322A, and P331S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at positions S267E and L328F, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at position C127S, wherein the numbering of the residue positions is according to EU numbering. In some embodiments, the Fc region contains amino acid substitutions at positions E345R, E430G, and S440Y, wherein the numbering of the residue positions is according to EU numbering.

[0244] In some preferred embodiments, the Fc region contains amino acid substitutions at positions S267E and L328F, wherein the numbering of the residue positions is according to EU numbering.

[0245] Inert antibodies

[0246] Another category of anti-Siglec-7 antibodies disclosed herein includes inert antibodies. As used herein, an "inert" antibody refers to an antibody that specifically binds to its target antigen (e.g., Siglec-7) but does not modulate (e.g., reduce / inhibit or activate / induce) the function of the antigen. For example, in the case of Siglec-7, an inert antibody does not modulate the cellular level of Siglec-7, does not modulate the interaction (e.g., binding) between Siglec-7 and one or more Siglec-7 ligands, or does not modulate one or more activities of the Siglec-7 protein. In some embodiments, antibodies that do not have the ability to cluster Siglec-7 on the cell surface can be inert antibodies, even if they have epitope specificity compatible with receptor activation.

[0247] In some embodiments, antibodies that bind to Siglec-7 proteins may include antibodies that bind to Siglec-7 but, due to their epitope specificity or properties, do not reduce the cellular level of Siglec-7 and / or inhibit the interaction (e.g., binding) between Siglec-7 and one or more Siglec-7 ligands. In some embodiments, such antibodies can be used as cargo to, for example, transport toxins (e.g., chemotherapeutic agents) into tumor cells. Thus, in some embodiments, the antibodies of the present disclosure are inert antibodies that bind to Siglec-7 but cannot reduce the cellular level of Siglec-7, inhibit the interaction (e.g., binding) between Siglec-7 and one or more Siglec-7 ligands, or induce one or more activities of the Siglec-7 protein.

[0248] Antibodies that reduce or do not reduce the cellular level of Siglec-7 on cells can be combined with an inert Fc region that exhibits reduced binding to one or more Fcγ receptors. Examples of such Fc regions and modifications are provided below in Table C. In some embodiments, the antibodies with an inert Fc region have an Fc isotype listed in Table C.

[0249] Inhibitory anti-Siglec-7 antibodies

[0250] The third class of anti-Siglec-7 antibodies disclosed herein includes antibodies that block or otherwise inhibit one or more Siglec-7 activities. In some embodiments, antibodies that bind to Siglec-7 proteins may include antibodies that reduce the cellular level of Siglec-7 (e.g., cell surface levels of Siglec-7), inhibit the interaction between Siglec-7 and / or one or more Siglec-7 ligands (e.g., binding) and inhibit one or more activities of Siglec-7 proteins. Such antibodies inhibit one or more activities of Siglec-7 proteins by preventing the interaction (e.g., binding) between Siglec-7 and one or more Siglec-7 ligands in the presence of one or more Siglec-7 ligands or by preventing signal transduction from the extracellular domain of Siglec-7 into the cytoplasm. The antibodies may also inhibit one or more activities of the Siglec-7 protein by reducing the cell surface level of Siglec-7, inducing Siglec-7 degradation, Siglec-7 desensitization, Siglec-7 cleavage, Siglec-7 internalization, Siglec-7 shedding, downregulation of Siglec-7 expression, and / or lysosomal degradation of Siglec-7. In some embodiments, such anti-Siglec-7 antibodies may not transiently activate Siglec-7.

[0251] In some embodiments, the anti-Siglec-7 antibodies of the disclosure may have the epitope specificity of the transient agonist anti-Siglec-7 antibodies of the disclosure, but have an Fc domain that is unable to bind Fcγ receptors and therefore cannot, for example, transiently cluster and activate Siglec-7.

[0252] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have, but are not limited to, one or more of the following activities: reducing the ability of Siglec-7 protein to bind to one or more Siglec-7 ligands, such as sialic acid-containing glycolipids or sialic acid-containing glycoproteins; reducing the ability of cytokine signaling inhibitor (SOCS) protein (e.g., SOCS3 protein) to bind to Siglec-7 protein; increasing the ability of proteasomal degradation of Siglec-7 protein; reducing the expression of proteins on the surface of circulating dendritic cells, macrophages, monocytes, T cells and / or microglial cells. The ability of Siglec-7 to functionally express; reduce the ability of Src family tyrosine kinases such as Syk, LCK, FYM and / or ZAP70 to phosphorylate Tyr-437 and Tyr-460; reduce the ability to recruit and bind to the tyrosine-specific protein phosphatases SHP1 and SHP2; reduce the ability to recruit and bind to PLC-g1, which acts as a guanine nucleotide exchange factor for dynamin-1; reduce the ability to recruit and bind to Crkl; reduce the ability to recruit and bind to the spleen tyrosine kinase Syk; reduce the ability to recruit and bind to SH3-S The ability to inhibit H2-SH3 growth factor receptor binding protein 2 (Grb2); reduce the ability to recruit and bind to various SH2-containing proteins; increase the ability to mobilize intracellular calcium; regulate the production of proinflammatory cytokines IL-1β, IL-8 and TNF-α; reduce the activation of phosphoinositide 3-kinase; increase the growth of monocytes, macrophages, dendritic cells, T cells and / or microglia; increase the survival of monocytes, macrophages, dendritic cells, T cells and / or microglia; and increase tyrosine phosphorylation on various cellular proteins. ; the ability to increase the phagocytic activity of monocytes, macrophages, dendritic cells and / or microglial cells; the ability to increase the proliferation of monocytes, macrophages, dendritic cells, T cells and / or microglial cells; the ability to increase the phosphorylation of signaling molecules that mediate ITAM signaling; the ability to increase the function of pattern recognition receptors; the ability to increase the function of Toll-like receptors; the ability to increase the function of damage-associated molecular pattern (DAMP) receptors; the ability to modulate the expression of CC chemokine receptor 7 (CCR7); and the ability to increase the clearance of cellular debris and protein debris.

[0253] In some embodiments, the anti-Siglec-7 antibodies of the present disclosure have an Fc region that exhibits reduced binding to one or more Fcγ receptors. Examples of such Fc regions and modifications are provided below in Table C. In some embodiments, the antibodies have an Fc isotype listed in Table C.

[0254] Antibody Fc isotypes with reduced binding to Fcγ receptors

[0255] In some embodiments, the anti-Siglec-7 antibody with reduced binding to an Fcγ receptor has an Fc isotype listed in Table C below.

[0256] Table C: Exemplary anti-Siglec-7 antibody Fc isotypes with reduced binding to Fcγ receptors

[0257]

[0258]

[0259] In certain embodiments, the anti-Siglec-7 antibody has an IgG1 isotype. In some embodiments, the antibody contains a mouse IgG1 constant region. In some embodiments, the antibody contains a human IgG1 constant region. In some embodiments, the human IgG1 constant region includes an Fc region. In some embodiments, the Fc region contains one or more modifications. For example, in some embodiments, the Fc region contains one or more amino acid substitutions (e.g., relative to a wild-type Fc region of the same isotype).

[0260] In some embodiments, the one or more amino acid substitutions are selected from N297A, N297Q (Bolt S et al. (1993) Eur J Immunol 23:403-411), D265A, D270A, L234A, L235A (McEarchern et al., (2007) Blood, 109: 1185-1192), C226S, C229S (McEarchern et al., (2007) Blood, 109: 1185-1192), P238S (Davis et al., (2007) J Rheumatol, 34:2204-2210), E233P, L234V (McEarchern et al., (2007) Blood, 109:1185-1192), P238A, A327Q, A327G, P329A (Shields RL, et al., (2001) J Biol Chem. 276(9):6591-604), K322A, L234F, L235E (Hezareh, et al., (2001) J Virol 75, 12161-12168; Oganesyan et al., (2008) Acta Crystallographica 64, 700-704), P331S (Oganesyan et al., (2008) Acta Crystallographica 64,700–704), T394D (Wilkinson et al. (2013) MAbs 5(3):406–417), A330L, M252Y, S254T, and / or T256E, wherein the amino acid positions are according to the EU or Kabat numbering convention. In certain embodiments, the Fc region further comprises an amino acid deletion at a position corresponding to glycine 236 according to the EU or Kabat numbering convention.

[0261] In some embodiments, the anti-Siglec-7 antibody has an IgG1 isotype having a heavy chain constant region comprising a C220S amino acid substitution according to the EU or Kabat numbering convention. In some embodiments, the Fc region further contains one or more additional amino acid substitutions selected from A330L, L234F, L235E, or P331S according to the EU or Kabat numbering convention. In certain embodiments, the anti-Siglec-7 antibody has an IgG2 isotype. In some embodiments, the anti-Siglec-7 antibody contains a human IgG2 constant region. In some embodiments, the human IgG2 constant region includes an Fc region. In some embodiments, the Fc region contains one or more modifications. For example, in some embodiments, the Fc region contains one or more amino acid substitutions (e.g., relative to a wild-type Fc region of the same isotype). In some embodiments, the one or more amino acid substitutions are selected from P238S, V234A, G237A, H268A, H268Q, H268E, V309L, N297A, N297Q, V309L, A330S, P331S, C232S, C233S, M252Y, S254T and / or T256E, wherein the amino acid positions are numbered according to the EU or Kabat convention (Vafa O. et al., (2014) Methods 65: 114–126).

[0262] In certain embodiments, the anti-Siglec-7 antibody has an IgG4 isotype. In some embodiments, the anti-Siglec-7 antibody contains a human IgG4 constant region. In some embodiments, the human IgG4 constant region includes an Fc region. In some embodiments, the Fc region contains one or more modifications. For example, in some embodiments, the Fc region contains one or more amino acid substitutions (e.g., relative to a wild-type Fc region of the same isotype). In some embodiments, the one or more amino acid substitutions are selected from E233P, F234V, L235A, G237A, E318A (Hutchins et al. (1995) Proc Natl Acad Sci USA, 92: 11980-11984), S228P, L234A / F234A, L236E, S241P, L248E (Reddy et al., (2000) J Immunol, 164: 1925-1933; Angal et al., (1993) Mol Immunol. 30(1): 105-8; US8614299B2; Vafa O. et al., (2014) Methods 65:114–126), T394D, M252Y, S254T, T256E, N297A, and / or N297Q, wherein the amino acid positions are numbered according to EU or Kabat. In some embodiments, the antibody has an IgG4 isotype and comprises an S228P amino acid substitution at residue position 228, an F234A amino acid substitution at residue position 234, and an L235A amino acid substitution at residue position 235 (residue positions are numbered according to EU).

[0263] In some embodiments, the Fc region further contains one or more additional amino acid substitutions selected from M252Y, S254T, and / or T256E, wherein the amino acid positions are according to the EU or Kabat numbering convention.

[0264] Other IgG mutations

[0265] In some embodiments, one or more IgG1 variants described herein may be combined with an A330L mutation (Lazar et al., (2006) Proc Natl Acad Sci USA, 103:4005-4010) or one or more of the L234F, L235E, and / or P331S mutations (Sazinsky et al., (2008) Proc Natl Acad Sci USA, 105:20167-20172) to eliminate complement activation, wherein the amino acid positions are according to the EU or Kabat numbering convention. In some embodiments, the IgG variants described herein can be combined with one or more mutations to enhance the anti-Siglec-7 antibody half-life in human serum (e.g., M252Y, S254T, T256E mutations according to EU or Kabat numbering conventions) (Dall'Acqua et al., (2006) J Biol Chem, 281: 23514-23524; and Strohl et al., (2009) Current Opinion in Biotechnology, 20: 685–691).

[0266] In some embodiments, the IgG4 variants of the present disclosure may be combined with an S228P mutation according to the EU or Kabat numbering convention (Angal et al., (1993) Mol Immunol, 30: 105-108), and / or with one or more mutations described in Peters et al., (2012) J Biol Chem. 13; 287(29): 24525-33) to enhance antibody stabilization.

[0267] Bispecific antibodies

[0268] Certain aspects of the present disclosure relate to bispecific antibodies that bind to one or more domains on the Siglec-7 protein of the present disclosure and a second antigen. Methods for producing bispecific antibodies are well known in the art and described herein. In some embodiments, the bispecific antibodies of the present disclosure bind to one or more amino acid residues of the Siglec-7 protein of the present disclosure, such as one or more amino acid residues of human Siglec-7 (SEQ ID NO: 63), or amino acid residues on the Siglec-7 protein corresponding to the amino acid residues of SEQ ID NO: 63. In some embodiments, the bispecific antibodies of the present disclosure recognize a first antigen and a second antigen. In some embodiments, the first antigen is a Siglec-7 protein or a naturally occurring variant thereof. In some embodiments, the second antigen is also a Siglec-7 protein or a naturally occurring variant thereof. In some embodiments, the second antigen is an antigen that promotes transport across the blood-brain barrier (see, for example, Gabathuler R., Neurobiol. Dis. 37 (2010) 48-57). Such secondary antigens include, but are not limited to, transferrin receptor (TR), insulin receptor (HIR), insulin-like growth factor receptor (IGFR), low-density lipoprotein receptor-related proteins 1 and 2 (LPR-1 and 2), diphtheria toxin receptor, CRM197, llama single domain antibodies, TMEM 30(A), protein transduction domain, TAT, Syn-B, penetratin, polyarginine peptides, angiopoietin peptides such as ANG1005 (see, e.g., Gabathuler, 2010), and other cell surface proteins enriched on blood-brain barrier endothelial cells (see, e.g., Daneman et al., PLoS One. 2010 Oct 29;5(10):e13741).In some embodiments, the second antigen is a pathogenic protein, including but not limited to amyloid beta, oligomeric amyloid beta, amyloid beta plaques, amyloid precursor protein or fragments thereof, Tau, IAPP, α-synuclein, TDP-43, FUS protein, C9orf72 (chromosome 9 open reading frame 72), c9RAN protein, prion protein, PrPSc, huntingtin protein, calcitonin, superoxide dismutase, ataxia, ataxia 1, ataxia 2, ataxia 3, ataxia 7, ataxia 8, ataxia 10, Lewy bodies, atrial natriuretic factor, pancreatic Islet amyloid polypeptide, insulin, apolipoprotein AI, serum amyloid A, interferon, prolactin, transthyretin, lysozyme, β2-microglobulin, gelsolin, corneal epithelial protein, cystatin, immunoglobulin light chain AL, S-IBM protein, repeat-associated non-ATG (RAN) translation products, dipeptide repeat (DPR) peptide, glycine-alanine (GA) repeat peptide, glycine-proline (GP) repeat peptide, glycine-arginine (GR) repeat peptide, proline-alanine (PA) repeat peptide, ubiquitin, and proline-arginine (PR) repeat peptide. In some embodiments, the second antigen is one or more ligands and / or proteins expressed on immune cells, including but not limited to CD33, CD40, OX40, ICOS, CD28, CD137 / 4-1BB, CD27, GITR, PD-L1, CTLA4, PD-L2, PD-1, B7-H3, B7-H4, HVEM, LIGHT, BTLA, CD38, TIGIT, VISTA, KIR, GAL9, TIM1, TIM3, TIM4, A2AR, LAG3, DR5, CD39, CD70, CD73, TREM1, TREM2, Siglec-5, Siglec-9, Siglec-11, SirpA, CD47, CSF1 receptor, CD3 and phosphatidylserine. In some embodiments, the second antigen is a protein, lipid, polysaccharide or glycolipid expressed on one or more tumor cells.

[0269] Antibody fragments

[0270] Certain aspects of the present disclosure relate to antibody fragments that bind to one or more of the Siglec-7 proteins, naturally occurring variants of Siglec-7 proteins, and disease variants of Siglec-7 proteins disclosed herein. In some embodiments, the antibody fragment is a Fab, Fab', Fab'-SH, F(ab')2, Fv, or scFv fragment.

[0271] In some embodiments, the antibody fragment is used in combination with a second Siglec-7 antibody and / or with one or more antibodies that specifically bind to a pathogenic protein, the pathogenic protein being selected from the group consisting of amyloid beta, oligomeric amyloid beta, amyloid beta plaques, amyloid precursor protein or fragments thereof, Tau, IAPP, α-synuclein, TDP-43, FUS protein, C9orf72 (chromosome 9 open reading frame 72), c9RAN protein, prion protein, PrPSc, huntingtin protein, calcitonin, superoxide dismutase, ataxia Dysregulation, ataxin 1, ataxin 2, atax...

Claims

1. An antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises: HVR-H1 comprising a sequence according to Formula I: GYAFTX1X2WMN (SEQ ID NO:6), wherein X1 is E, M, G or A, and X2 is T, A or Y; HVR-H2 comprising a sequence according to Formula II: RIFPGX1GHTN (SEQ ID NO:9), wherein X1 is L or Y; and HVR-H3 comprising the sequence of DYSDYYFDY (SEQ ID NO: 10); and The light chain variable region comprises: HVR-L1 comprising a sequence according to Formula III: RX1SX2DX3NTYLN (SEQ ID NO: 15), wherein X1 is G or A, X2 is Q or E, and X3 is I, T or A; HVR-L2 comprising the sequence of YTSRLHS (SEQ ID NO: 16); and HVR-L3, comprising a sequence according to Formula IV: QX1GX2X3X4PWT (SEQ ID NO:24), wherein X1 is Q or G, X2 is N or G, X3 is L, T, V or I, and X4 is L or K.

2. An antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises: HVR-H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5; HVR-H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 7-8; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 10; and The light chain variable region comprises: HVR-L1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 11-14; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 16; and HVR-L3, comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 17-23.

3. The antibody according to any one of claims 1 to 2, wherein: (a) the HVR-H1 comprises the amino acid sequence of GYAFTMAWMN (SEQ ID NO:2), the HVR-H2 comprises the amino acid sequence of RIFPGYGHTN (SEQ ID NO:8), the HVR-H3 comprises the amino acid sequence of DYSDYYFDY (SEQ ID NO:10), the HVR-L1 comprises the amino acid sequence of RGSQDINTYLN (SEQ ID NO:11), the HVR-L2 comprises the amino acid sequence of YTSRLHS (SEQ ID NO:16), and the HVR-L3 comprises the amino acid sequence of QQGNLLPWT (SEQ ID NO:17); (b) the HVR-H1 comprises the amino acid sequence of GYAFTGYWMN (SEQ ID NO:3), the HVR-H2 comprises the amino acid sequence of RIFPGLGHTN (SEQ ID NO:7), the HVR-H3 comprises the amino acid sequence of DYSDYYFDY (SEQ ID NO:10), the HVR-L1 comprises the amino acid sequence of RGSQDTNTYLN (SEQ ID NO:12), the HVR-L2 comprises the amino acid sequence of YTSRLHS (SEQ ID NO:16), and the HVR-L3 comprises the amino acid sequence of QQGNTLPWT (SEQ ID NO:20); (c) the HVR-H1 comprises the amino acid sequence of GYAFTGYWMN (SEQ ID NO:3), the HVR-H2 comprises the amino acid sequence of RIFPGLGHTN (SEQ ID NO:7), the HVR-H3 comprises the amino acid sequence of DYSDYYFDY (SEQ ID NO:10), the HVR-L1 comprises the amino acid sequence of RGSQDINTYLN (SEQ ID NO:11), the HVR-L2 comprises the amino acid sequence of YTSRLHS (SEQ ID NO:16), and the HVR-L3 comprises the amino acid sequence of QQGNILPWT (SEQ ID NO:23); or (d) the HVR-H1 comprises the amino acid sequence of GYAFTAAWMN (SEQ ID NO:4), the HVR-H2 comprises the amino acid sequence of RIFPGLGHTN (SEQ ID NO:7), the HVR-H3 comprises the amino acid sequence of DYSDYYFDY (SEQ ID NO:10), the HVR-L1 comprises the amino acid sequence of RGSQDINTYLN (SEQ ID NO:11), the HVR-L2 comprises the amino acid sequence of YTSRLHS (SEQ ID NO:16), and the HVR-L3 comprises the amino acid sequence of QQGNILPWT (SEQ ID NO:23).

4. An antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein: The heavy chain variable region comprises HVR-H1, which comprises the amino acid sequence GYAFTMAWMN (SEQ ID NO:2); HVR-H2, which comprises the amino acid sequence RIFPGYGHTN (SEQ ID NO:8), and HVR-H3, which comprises the amino acid sequence DYSDYYFDY (SEQ ID NO:10), and the light chain variable region comprises HVR-L1, which comprises the amino acid sequence RGSQDINTYLN (SEQ ID NO:11); HVR-L2, which comprises the amino acid sequence YTSRLHS (SEQ ID NO:16); and HVR-L3, which comprises the amino acid sequence QQGNLLPWT (SEQ ID NO:17).

5. An antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein: The heavy chain variable region comprises HVR-H1, which comprises the amino acid sequence GYAFTGYWMN (SEQ ID NO:3); HVR-H2, which comprises the amino acid sequence RIFPGLGHTN (SEQ ID NO:7), and HVR-H3, which comprises the amino acid sequence DYSDYYFDY (SEQ ID NO:10), and the light chain variable region comprises HVR-L1, which comprises the amino acid sequence RGSQDTNTYLN (SEQ ID NO:12); HVR-L2, which comprises the amino acid sequence YTSRLHS (SEQ ID NO:16); and HVR-L3, which comprises the amino acid sequence QQGNTLPWT (SEQ ID NO:20).

6. An antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein: The heavy chain variable region comprises HVR-H1, which comprises the amino acid sequence of GYAFTGYWMN (SEQ ID NO:3); HVR-H2, which comprises the amino acid sequence of RIFPGLGHTN (SEQ ID NO:7), and HVR-H3, which comprises the amino acid sequence of DYSDYYFDY (SEQ ID NO:10), and the light chain variable region comprises HVR-L1, which comprises the amino acid sequence of RGSQDINTYLN (SEQ ID NO:11); HVR-L2, which comprises the amino acid sequence of YTSRLHS (SEQ ID NO:16); and HVR-L3, which comprises the amino acid sequence of QQGNILPWT (SEQ ID NO:23).

7. An antibody that binds to a Siglec-7 protein, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein: The heavy chain variable region comprises HVR-H1, which comprises the amino acid sequence GYAFTAAWMN (SEQ ID NO:4); HVR-H2, which comprises the amino acid sequence RIFPGLGHTN (SEQ ID NO:7), and HVR-H3, which comprises the amino acid sequence DYSDYYFDY (SEQ ID NO:10), and the light chain variable region comprises HVR-L1, which comprises the amino acid sequence RGSQDINTYLN (SEQ ID NO:11); HVR-L2, which comprises the amino acid sequence YTSRLHS (SEQ ID NO:16); and HVR-L3, which comprises the amino acid sequence QQGNILPWT (SEQ ID NO:23).

8. The antibody of any one of claims 1-7, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 36-48; and / or a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 49-60.

9. The antibody of claim 8, wherein the antibody comprises: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 41 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 52; a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55; a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 42 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 60; or a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 43 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:

60.

10. An antibody that binds to a Siglec-7 protein, wherein the antibody comprises: a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:41 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:52.

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