Antibody molecules against complement component 5 and their uses

Abstract

Disclosed are antibody molecules that specifically bind to C5. The antibody molecules can be used for treating, preventing, and / or diagnosing disorders such as complement-related disorders.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 686,982, filed on Jun. 19, 2018. The content of the foregoing application is incorporated herein by reference in its entirety.

[0003] Sequence Listing

[0004] This application contains a Sequence Listing that has been submitted electronically in ASCII format and is incorporated herein by reference in its entirety. The ASCII copy was created on Jun. 19, 2019, named A2176-7000WQ_SL, and is 101,767 bytes in size. BACKGROUND OF THE INVENTION

[0005] Complement proteins are part of the innate immune response. They exert a series of biological functions (such as opsonization (coating of foreign pathogens), initiation of the membrane attack complex, and enhancement of inflammation) by activating different pathways: classical, lectin, and alternative. The complement pathways converge into a common pathway that causes the cleavage or activation of C3 to produce C3a or C3b, leading to the formation of various bioactive molecules such as C5a and C5b. Experimental studies have shown that blocking the cleavage of C5 into C5a and C5b can have an anti-inflammatory effect without affecting the activation and function of early components (e.g., Rother RP et al., Nature Biotechnology 2007; 25(11):1256-1264, Fukuzawa T et al., Sci Rep. 2017; 7(1):1080; each incorporated herein by reference in its entirety). There is a need to develop new methods for treating, preventing, and diagnosing complement-related disorders and other disorders sharing similar disease mechanisms. SUMMARY OF THE INVENTION

[0006] The present disclosure provides, at least in part, an antibody molecule that binds to complement component 5 (C5), such as human C5 (e.g., human C5 comprising the amino acid sequence of SEQ ID NO:53), and comprises one or more of the functional and structural properties disclosed herein. In one embodiment, the antibody molecule binds to C5 and / or reduces (e.g., inhibits, blocks, or neutralizes) one or more of its activities. In one embodiment, the antibody molecule is selected from Table 1, or competes with an antibody molecule selected from Table 1 for binding to C5. In one embodiment, the antibody molecule binds to an epitope that is the same as or overlaps with the epitope recognized by an antibody molecule selected from Table 1. In one embodiment, the antibody molecule comprises one or more heavy chain variable regions and / or one or more light chain variable regions described in Table 1. In one embodiment, the antibody molecule comprises one or more heavy chain CDRs and / or one or more light chain CDRs described in Table 1. In one embodiment, there are also provided nucleic acid molecules, expression vectors, host cells, compositions (e.g., pharmaceutical compositions), kits, containers, and methods for preparing the antibody molecule. The antibody molecules disclosed herein are suitable for reducing or inhibiting the unwanted activation of the complement system or its components. The antibody molecules disclosed herein can be used (alone or in combination with other agents or treatment modalities) for treating, preventing, and / or diagnosing complement-related disorders.

[0007] Thus, in one aspect, the present disclosure provides an antibody molecule, such as the antibody molecules described herein, having one or more of the following properties (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or all):

[0008] a) binds to C5 (e.g., human C5) with high affinity, such as with a dissociation constant (K D'), e.g., about 20 nM or lower, 10 nM or lower, 9 nM or lower, 8 nM or lower, 7 nM or lower, 6 nM or lower, 5 nM or lower, 4 nM or lower, 3 nM or lower, 2 nM or lower, 1 nM or lower, 0.5 nM or lower, 0.2 nM or lower, 0.1 nM or lower, 0.05 nM or lower, 0.02 nM or lower, 0.01 nM or lower, 0.005 nM or lower, 0.002 nM or lower, or 0.001 nM or lower, e.g., between 0.001 nM and 10 nM, between 0.001 nM and 5 nM, between 0.001 nM and 2 nM, between 0.001 nM and 1 nM, between 0.001 nM and 0.5 nM, between 0.001 nM and 0.2 nM, between 0.001 nM and 0.1 nM, between 0.001 and 0.05 nM, between 0.001 and 0.02 nM, between 0.001 and 0.005 nM, between 5 nM and 10 nM, between 2 nM and 10 nM, between 1 nM and 10 nM, between 0.5 nM and 10 nM, between 0.2 nM and 10 nM, between 0.1 nM and 10 nM, between 0.05 nM and 10 nM, between 0.02 nM and 10 nM, between 0.01 nM and 10 nM, between 0.005 nM and 10 nM, between 0.002 and 10 nM, between 0.002 nM and 5 nM, between 0.005 nM and 2 nM, between 0.01 nM and 1 nM, between 0.02 nM and 0.5 nM, between 0.05 nM and 0.2 nM, between 0.001 nM and 0.002 nM, between 0.002 nM and 0.005 nM, between 0.005 nM and 0.01 nM, between 0.01 nM and 0.02 nM, between 0.02 nM and 0.05 nM, between 0.05 nM and 0.1 nM, between 0.1 nM and 0.2 nM, between 0.2 nM and 0.5 nM, between 0.5 nM and 1 nM, between 1 nM and 2 nM, between 2 nM and 5 nM, or between 5 nM and 10 nM, e.g., between 0.1 nM and 0.6 nM or between 0.2 nM and 0.53 nM, e.g., as determined by the methods described herein;

[0009] b) binds to C5 (e.g., human C5) at a neutral pH with an affinity that is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 - fold higher than the affinity at an acidic pH (e.g., a pH lower than 7, 6.5, 6, 5.5, 5, or lower);

[0010] c) binds to C5 (e.g., human C5) with high affinity, e.g., with a half - maximal effective concentration (EC 50), for example, about 1 μg / ml or lower, 0.9 μg / ml or lower, 0.8 μg / ml or lower, 0.7 μg / ml or lower, 0.6 μg / ml or lower, 0.5 μg / ml or lower, 0.4 μg / ml or lower, 0.3 μg / ml or lower, 0.2 μg / ml or lower, 0.1 μg / ml or lower, 0.09 μg / ml or lower, 0.08 μg / ml or lower, 0.07 μg / ml or lower, 0.06 μg / ml or lower, 0.05 μg / ml or lower, 0.04 μg / ml or lower, 0.03 μg / ml or lower, 0.02 μg / ml or lower, 0.01 μg / ml or lower, 0.005 μg / ml or lower, 0.002 μg / ml or lower, 0.001 μg / ml or lower, for example, between 0.001 μg / ml and 2 μg / ml, for example, between 0.001 μg / ml and 1 μg / ml, between 0.001 μg / ml and 0.5 μg / ml, between 0.001 μg / ml and 0.2 μg / ml, between 0.001 μg / ml and 0.1 μg / ml, between 0.001 μg / ml and 0.05 μg / ml, between 0.001 μg / ml and 0.02 μg / ml, between 0.001 μg / ml and 0.01 μg / ml, between 0.001 μg / ml and 0.005 μg / ml, between 0.002 μg / ml and 1 μg / ml, between 0.005 μg / ml and 1 μg / ml, between 0.01 μg / ml and 1 μg / ml, between 0.02 μg / ml and 1 μg / ml, between 0.05 μg / ml and 1 μg / ml, between 0.1 μg / ml and 1 μg / ml, between 0.2 μg / ml and 1 μg / ml, between 0.5 μg / ml and 1 μg / ml, between 0.001 μg / ml and 1 μg / ml, between 0.002 μg / ml and 0.5 μg / ml, between 0.005 μg / ml and 0.2 μg / ml, between 0.01 μg / ml and 0.1 μg / ml or between 0.02 μg / ml and 0.05 μg / ml, for example, determined by the methods described herein;

[0011] d) specifically binds to an epitope on C5 (such as human C5), for example, an epitope that is the same as, similar to, or overlaps with the epitope recognized by the monoclonal antibodies described in Table 1 (such as any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013);

[0012] e) reducing (e.g., inhibiting, blocking or neutralizing) one or more biological activities of C5 (e.g., human C5) in vitro, ex vivo or in vivo;

[0013] f) reducing (e.g., inhibiting, blocking or neutralizing) one or more biological activities of C5 (e.g., human C5), e.g., at a half maximal inhibitory concentration (IC 50), for example, about 20 μg / ml or lower, 10 μg / ml or lower, 9 μg / ml or lower, 8 μg / ml or lower, 7 μg / ml or lower, 6 μg / ml or lower, 5 μg / ml or lower, 4 μg / ml or lower, 3 μg / ml or lower, 2 μg / ml or lower, 1 μg / ml or lower, 0.5 μg / ml or lower, 0.2 μg / ml or lower, 0.1 μg / ml or lower, 0.05 μg / ml or lower, 0.02 μg / ml or lower, 0.01 μg / ml or lower, 0.005 μg / ml or lower, 0.002 μg / ml or lower, or 0.001 μg / ml or lower, for example, between 0.001 μg / ml and 10 μg / ml, between 0.001 μg / ml and 5 μg / ml, between 0.001 μg / ml and 2 μg / ml, between 0.001 μg / ml and 1 μg / ml, between 0.001 μg / ml and 0.5 μg / ml, between 0.001 μg / ml and 0.2 μg / ml, between 0.001 μg / ml and 0.1 μg / ml, between 0.001 and 0.05 μg / ml, between 0.001 and 0.02 μg / ml, between 0.001 and 0.005 μg / ml, between 5 μg / ml and 10 μg / ml, between 2 μg / ml and 10 μg / ml, between 1 μg / ml and 10 μg / ml, between 0.5 μg / ml and 10 μg / ml, between 0.2 μg / ml and 10 μg / ml, between 0.1 μg / ml and 10 μg / ml, between 0.05 μg / ml and 10 μg / ml, between 0.02 μg / ml and 10 μg / ml, between 0.01 μg / ml and 10 μg / ml, between 0.005 μg / ml and 10 μg / ml, between 0.002 and 10 μg / ml, between 0.002 μg / ml and 5 μg / ml, between 0.005 μg / ml and 2 μg / ml, between 0.01 μg / ml and 1 μg / ml, between 0.02 μg / ml and 0.5 μg / ml, between 0.05 μg / ml and 0.2 μg / ml, between 0.001 μg / ml and 0.002 μg / ml, between 0.002 μg / ml and 0.005 μg / ml, between 0.005 μg / ml and 0.01 μg / ml, between 0.01 μg / ml and 0.02 μg / ml, between 0.02 μg / ml and 0.05 μg / ml, between 0.05 μg / ml and 0.1 μg / ml, between 0.1 μg / ml and 0.2 μg / ml, between 0.2 μg / ml and 0.5 μg / ml, between 0.between 5 μg / ml and 1 μg / ml, between 1 μg / ml and 2 μg / ml, between 2 μg / ml and 5 μg / ml or between 5 μg / ml and 10 μg / ml, such as between 1 μg / ml and 8 μg / ml or between 2 μg / ml and 6 μg / ml, e.g., determined by the methods described herein;

[0014] g) exhibit the same or similar binding affinity and / or specificity or both thereof as the monoclonal antibodies described in Table 1 (e.g., any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013);

[0015] h) exhibit the same or similar binding affinity and / or specificity or both thereof as an antibody molecule comprising the heavy chain variable region and / or light chain variable region described in Table 1 (e.g., the heavy chain variable region and / or light chain variable region of any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013);

[0016] i) exhibit the same or similar binding affinity and / or specificity or both thereof as an antibody molecule comprising one or more (e.g., two or three) heavy chain CDRs and / or one or more (e.g., two or three) light chain CDRs (e.g., one or more (e.g., two or three) heavy chain CDRs and / or one or more (two or three) light chain CDRs of any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013);

[0017] j) exhibit the same or similar binding affinity and / or specificity or both thereof as an antibody molecule comprising the amino acid sequence shown in Table 1;

[0018] k) exhibit the same or similar binding affinity and / or specificity or both thereof as an antibody molecule comprising the amino acid sequence encoded by the nucleotide sequence shown in Table 5;

[0019] l) Inhibit, for example, competitively inhibit the binding of a second antibody molecule to C5 (such as human C5), for example, human C5, wherein the second antibody molecule is an antibody molecule selected from Table 1, for example, any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013;

[0020] m) Compete with a second antibody molecule for binding to C5 (such as human C5), wherein the second antibody molecule is a monoclonal antibody selected from Table 1, for example, any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013;

[0021] n) Have one or more biological properties of a monoclonal antibody selected from Table 1 (for example, any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013);

[0022] o) Have one or more structural properties of a monoclonal antibody selected from Table 1 (for example, any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013); or

[0023] p) Have one or more pharmacokinetic properties of a monoclonal antibody selected from Table 1 (for example, any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013).

[0024] In one embodiment, the antibody molecule binds to C5 (such as human C5) with high affinity, for example, with a K of about 50 nM or lower D', e.g., about 20 nM or lower, 10 nM or lower, 9 nM or lower, 8 nM or lower, 7 nM or lower, 6 nM or lower, 5 nM or lower, 4 nM or lower, 3 nM or lower, 2 nM or lower, 1 nM or lower, 0.5 nM or lower, 0.2 nM or lower, 0.1 nM or lower, 0.05 nM or lower, 0.02 nM or lower, 0.01 nM or lower, 0.005 nM or lower, 0.002 nM or lower, or 0.001 nM or lower, e.g., between 0.001 nM and 10 nM, between 0.001 nM and 5 nM, between 0.001 nM and 2 nM, between 0.001 nM and 1 nM, between 0.001 nM and 0.5 nM, between 0.001 nM and 0.2 nM, between 0.001 nM and 0.1 nM, between 0.001 and 0.05 nM, between 0.001 and 0.02 nM, between 0.001 and 0.005 nM, between 5 nM and 10 nM, between 2 nM and 10 nM, between 1 nM and 10 nM, between 0.5 nM and 10 nM, between 0.2 nM and 10 nM, between 0.1 nM and 10 nM, between 0.05 nM and 10 nM, between 0.02 nM and 10 nM, between 0.01 nM and 10 nM, between 0.005 nM and 10 nM, between 0.002 and 10 nM, between 0.002 nM and 5 nM, between 0.005 nM and 2 nM, between 0.01 nM and 1 nM, between 0.02 nM and 0.5 nM, between 0.05 nM and 0.2 nM, between 0.001 nM and 0.002 nM, between 0.002 nM and 0.005 nM, between 0.005 nM and 0.01 nM, between 0.01 nM and 0.02 nM, between 0.02 nM and 0.05 nM, between 0.05 nM and 0.1 nM, between 0.1 nM and 0.2 nM, between 0.2 nM and 0.5 nM, between 0.5 nM and 1 nM, between 1 nM and 2 nM, between 2 nM and 5 nM, or between 5 nM and 10 nM, e.g., between 0.1 nM and 0.6 nM or between 0.2 nM and 0.53 nM, e.g., as determined by the methods described herein.

[0025] In one embodiment, at neutral pH, the antibody molecule binds to C5 (e.g., human C5) with an affinity that is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 times higher than the affinity at acidic pH (e.g., pH below 7, 6.5, 6, 5.5, 5, or lower).

[0026] In one embodiment, the antibody molecule binds to C5 (e.g., human C5) with high affinity, e.g., with an EC of about 2 μg / ml or lower50 , for example, about 1 μg / ml or lower, 0.9 μg / ml or lower, 0.8 μg / ml or lower, 0.7 μg / ml or lower, 0.6 μg / ml or lower, 0.5 μg / ml or lower, 0.4 μg / ml or lower, 0.3 μg / ml or lower, 0.2 μg / ml or lower, 0.1 μg / ml or lower, 0.09 μg / ml or lower, 0.08 μg / ml or lower, 0.07 μg / ml or lower, 0.06 μg / ml or lower, 0.05 μg / ml or lower, 0.04 μg / ml or lower, 0.03 μg / ml or lower, 0.02 μg / ml or lower, 0.01 μg / ml or lower, 0.005 μg / ml or lower, 0.002 μg / ml or lower, 0.001 μg / ml or lower, for example, between 0.001 μg / ml and 2 μg / ml, for example, between 0.001 μg / ml and 1 μg / ml, between 0.001 μg / ml and 0.5 μg / ml, between 0.001 μg / ml and 0.2 μg / ml, between 0.001 μg / ml and 0.1 μg / ml, between 0.001 μg / ml and 0.05 μg / ml, between 0.001 μg / ml and 0.02 μg / ml, between 0.001 μg / ml and 0.01 μg / ml, between 0.001 μg / ml and 0.005 μg / ml, between 0.002 μg / ml and 1 μg / ml, between 0.005 μg / ml and 1 μg / ml, between 0.01 μg / ml and 1 μg / ml, between 0.02 μg / ml and 1 μg / ml, between 0.05 μg / ml and 1 μg / ml, between 0.1 μg / ml and 1 μg / ml, between 0.2 μg / ml and 1 μg / ml, between 0.5 μg / ml and 1 μg / ml, between 0.001 μg / ml and 1 μg / ml, between 0.002 μg / ml and 0.5 μg / ml, between 0.005 μg / ml and 0.2 μg / ml, between 0.01 μg / ml and 0.1 μg / ml, or between 0.02 μg / ml and 0.05 μg / ml, for example, determined by the methods described herein.

[0027] In one embodiment, the antibody molecule specifically binds to an epitope on C5 (such as human C5), for example, an epitope that is the same as, similar to, or overlapping with the epitope recognized by the monoclonal antibodies described in Table 1 (such as any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013).

[0028] In one embodiment, the antibody molecule reduces (e.g., inhibits, blocks or neutralizes) one or more biological activities of C5 (e.g., human C5) in vitro, ex vivo or in vivo.

[0029] In one embodiment, the antibody molecule reduces (e.g., inhibits, blocks or neutralizes) one or more biological activities of C5 (e.g., human C5), e.g., with an IC of about 50 μg / ml or lower. 50, for example, about 20 μg / ml or lower, 10 μg / ml or lower, 9 μg / ml or lower, 8 μg / ml or lower, 7 μg / ml or lower, 6 μg / ml or lower, 5 μg / ml or lower, 4 μg / ml or lower, 3 μg / ml or lower, 2 μg / ml or lower, 1 μg / ml or lower, 0.5 μg / ml or lower, 0.2 μg / ml or lower, 0.1 μg / ml or lower, 0.05 μg / ml or lower, 0.02 μg / ml or lower, 0.01 μg / ml or lower, 0.005 μg / ml or lower, 0.002 μg / ml or lower, or 0.001 μg / ml or lower, for example, between 0.001 μg / ml and 10 μg / ml, between 0.001 μg / ml and 5 μg / ml, between 0.001 μg / ml and 2 μg / ml, between 0.001 μg / ml and 1 μg / ml, between 0.001 μg / ml and 0.5 μg / ml, between 0.001 μg / ml and 0.2 μg / ml, between 0.001 μg / ml and 0.1 μg / ml, between 0.001 and 0.05 μg / ml, between 0.001 and 0.02 μg / ml, between 0.001 and 0.005 μg / ml, between 5 μg / ml and 10 μg / ml, between 2 μg / ml and 10 μg / ml, between 1 μg / ml and 10 μg / ml, between 0.5 μg / ml and 10 μg / ml, between 0.2 μg / ml and 10 μg / ml, between 0.1 μg / ml and 10 μg / ml, between 0.05 μg / ml and 10 μg / ml, between 0.02 μg / ml and 10 μg / ml, between 0.01 μg / ml and 10 μg / ml, between 0.005 μg / ml and 10 μg / ml, between 0.002 and 10 μg / ml, between 0.002 μg / ml and 5 μg / ml, between 0.005 μg / ml and 2 μg / ml, between 0.01 μg / ml and 1 μg / ml, between 0.02 μg / ml and 0.5 μg / ml, between 0.05 μg / ml and 0.2 μg / ml, between 0.001 μg / ml and 0.002 μg / ml, between 0.002 μg / ml and 0.005 μg / ml, between 0.005 μg / ml and 0.01 μg / ml, between 0.01 μg / ml and 0.02 μg / ml, between 0.02 μg / ml and 0.05 μg / ml, between 0.05 μg / ml and 0.1 μg / ml, between 0.1 μg / ml and 0.2 μg / ml, between 0.2 μg / ml and 0.5 μg / ml, between 0.Between 5 μg / ml and 1 μg / ml, between 1 μg / ml and 2 μg / ml, between 2 μg / ml and 5 μg / ml, or between 5 μg / ml and 10 μg / ml, such as between 1 μg / ml and 8 μg / ml or between 2 μg / ml and 6 μg / ml, for example, determined by the methods described herein.

[0030] In one embodiment, the antibody molecule exhibits the same or similar binding affinity and / or specificity, or both, as the monoclonal antibodies described in Table 1 (e.g., any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013).

[0031] In one embodiment, the antibody molecule exhibits the same or similar binding affinity and / or specificity, or both, as an antibody molecule comprising the heavy chain variable region and / or light chain variable region described in Table 1 (e.g., the heavy chain variable region and / or light chain variable region of any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013).

[0032] In one embodiment, the antibody molecule exhibits the same or similar binding affinity and / or specificity, or both, as an antibody molecule comprising one or more (e.g., two or three) heavy chain CDRs and / or one or more (e.g., two or three) light chain CDRs described in Table 1 (e.g., one or more (e.g., two or three) heavy chain CDRs and / or one or more (two or three) light chain CDRs of any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013).

[0033] In one embodiment, the antibody molecule exhibits the same or similar binding affinity and / or specificity, or both, as an antibody molecule comprising the amino acid sequence shown in Table 1.

[0034] In one embodiment, the antibody molecule exhibits the same or similar binding affinity and / or specificity, or both, as an antibody molecule comprising the amino acid sequence encoded by the nucleotide sequence shown in Table 5.

[0035] In one embodiment, the antibody molecule inhibits (e.g., competitively inhibits) the binding of a second antibody molecule to C5 (e.g., human C5), wherein the second antibody molecule is an antibody molecule selected from Table 1, such as any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013.

[0036] In one embodiment, the antibody molecule competes with a second antibody molecule for binding to C5 (e.g., human C5), wherein the second antibody molecule is a monoclonal antibody selected from Table 1, such as any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013.

[0037] In one embodiment, the antibody molecule has one or more biological properties of a monoclonal antibody selected from Table 1 (such as any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013).

[0038] In one embodiment, the antibody molecule has one or more structural properties of a monoclonal antibody selected from Table 1 (such as any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013).

[0039] In one embodiment, the antibody molecule has one or more pharmacokinetic properties of a monoclonal antibody selected from Table 1 (such as any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013).

[0040] In one embodiment, the antibody molecule is a synthetic antibody molecule. In one embodiment, the antibody molecule is an isolated antibody molecule. In one embodiment, the antibody molecule is a recombinant antibody molecule. In one embodiment, the antibody molecule is a humanized antibody. In one embodiment, the antibody molecule is a monospecific antibody molecule. In one embodiment, the antibody molecule is a multispecific antibody molecule.

[0041] In some embodiments, an antibody molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3).

[0042] Wherein, the VH comprises one, two, or all of the following:

[0043] (i) HCDR1, which comprises the amino acid sequence:

[0044] GX1X2FX3X4X5Y,

[0045] wherein: X1 is Y, F, or H;

[0046] X2 is I or T;

[0047] X3 is S or T;

[0048] X4 is N, S, D, or G; and

[0049] X5 is F, N, or absent

[0050] (SEQ ID NO:87);

[0051] (ii) HCDR2, which comprises the amino acid sequence:

[0052] X1X2X3X4GX5,

[0053] wherein: X1 is L or N;

[0054] X2 is A or P;

[0055] X3 is G, T, or K;

[0056] X4 is S, D, N, T, or S; and

[0057] X5 is S, H, or D

[0058] (SEQ ID NO:88);

[0059] (iii) HCDR3, which comprises the amino acid sequence:

[0060] X1X2X3X4X5X6X7X8X9X 10 X 11 X 12 X 13 ,

[0061] wherein: X1 is Y or G;

[0062] X2 is P, Y, S, F, or W;

[0063] X3 is F, S or W;

[0064] X4 is G or P;

[0065] X5 is S, N or M;

[0066] X6 is S, W, T or D;

[0067] X7 is P, A or V;

[0068] X8 is N, M or absent;

[0069] X9 is W, D or absent;

[0070] X 10 is E, Y, A or absent;

[0071] X 11 is F, M or absent;

[0072] X 12 is D or absent; and

[0073] X 13 is Y, V or absent

[0074] (SEQ ID NO:89); and

[0075] wherein VL comprises one, two or all of the following: (iv) LCDR1, which comprises the amino acid sequence:

[0076] X1AX2X3X4IX5X6X7LX8,

[0077] wherein: X1 is R or G;

[0078] X2 is S or T;

[0079] X3 is Q or E;

[0080] X4 is N, S or G;

[0081] X5 is N or Y;

[0082] X6 is N or G;

[0083] X7 is Y or A; and

[0084] X8 is H, N or A

[0085] (SEQ ID NO:90);

[0086] (v) LCDR2, which comprises the amino acid sequence:

[0087] X1ASX2X3X4X5,

[0088] wherein: X1 is A, G or D;

[0089] X2 is N or T;

[0090] X3 is L or R;

[0091] X4 is Q, A, Y or E; or

[0092] X5 is G, D, T or S

[0093] (SEQ ID NO:91); and

[0094] (vi) LCDR3, which comprises the amino acid sequence:

[0095] X1X2X3X4X5X6PX7X8,

[0096] wherein: X1 is L or Q;

[0097] X2 is Q or N;

[0098] X3 is T or V;

[0099] X4 is H or L;

[0100] X5 is A, N or S;

[0101] X6 is Y or T;

[0102] X7 is L, V, W or Y; or

[0103] X8 is T or S

[0104] (SEQ ID NO:92).

[0105] In an embodiment, the antibody molecule comprises VH and VL, wherein VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3), and wherein VL comprises three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3),

[0106] wherein, VH comprises one, two or all of the following:

[0107] (i) HCDR1, which comprises the amino acid sequence:

[0108] X1X2X3X4X5

[0109] wherein: X1 is N, D, S or G;

[0110] X2 is Y, F or N;

[0111] X3 is W or Y;

[0112] X4 is M or I; and

[0113] X5 is Q or H

[0114] (SEQ ID NO:94);

[0115] (ii) HCDR2, which comprises the amino acid sequence:

[0116] X1X2X3X4X5X6GX7TX8YX9QKFX 10 G

[0117] wherein: X1 is E or W;

[0118] X2 is I or V;

[0119] X3 is L or N;

[0120] X4 is P or A;

[0121] X5 is G, T or K;

[0122] X6 is T, S, D or N;

[0123] X7 is S, H or D;

[0124] X8 is E or N;

[0125] X9 is A or S; and

[0126] X 10 is Q or R

[0127] (SEQ ID NO:95);

[0128] (iii) HCDR3, which comprises the amino acid sequence:

[0129] X1X2X3X4X5X6X7X8WX9X 10 DX 11

[0130] wherein: X1 is Y or G;

[0131] X2 is F, P, Y or W;

[0132] X3 is F or absent;

[0133] X4 is G or absent;

[0134] X5 is S or absent;

[0135] X6 is T, S or absent;

[0136] X7 is P or absent;

[0137] X8 is N or absent;

[0138] X9 is Y, E, A or G;

[0139] X 10 is F or M; and

[0140] X 11 is V or Y

[0141] (SEQ ID NO:96); and

[0142] wherein VL comprises one, two or all of the following: (iv) LCDR1, which comprises the amino acid sequence:

[0143] X1AX2X3X4IX5X6X7LX8

[0144] wherein: X1 is G or R;

[0145] X2 is T or S;

[0146] X3 is E or Q;

[0147] X4 is N, G or S;

[0148] X5 is Y or N;

[0149] X6 is G or N;

[0150] X7 is A or Y; and

[0151] X8 is N, A or H

[0152] (SEQ ID NO:97);

[0153] (v) LCDR2, which comprises the amino acid sequence:

[0154] X1ASX2X3X4X5

[0155] wherein: X1 is G, D or A;

[0156] X2 is N or T;

[0157] X3 is L or R;

[0158] X4 is A, Y, E or Q; and

[0159] X5 is D, T, S or G

[0160] (SEQ ID NO:98); and

[0161] (vi) LCDR3, which comprises the amino acid sequence:

[0162] X1X2X3X4X5X6PX7X8

[0163] Wherein: X1 is Q or L;

[0164] X2 is N or Q;

[0165] X3 is V or T;

[0166] X4 is L or H;

[0167] X5 is N, S or A;

[0168] X6 is T or Y;

[0169] X7 is L, V, W or Y; and

[0170] X8 is S or T

[0171] (SEQ ID NO:99).

[0172] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the VH comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:19) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:28) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0173] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 43) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 48) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0174] In one embodiment, the antibody molecule comprises:

[0175] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 19) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 28) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0176] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 38) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 43) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 48) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0177] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 19); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 28); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 38); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 43); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 48).

[0178] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 20) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 28) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0179] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 43) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 48) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0180] In one embodiment, the antibody molecule comprises:

[0181] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:20) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:28) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:35) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology, and

[0182] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:38) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:43) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:48) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0183] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:20); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:28); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:43); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:48).

[0184] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:21) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:29) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:35) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0185] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 43) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 48) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0186] In one embodiment, the antibody molecule comprises:

[0187] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 21) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0188] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 43) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 48) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0189] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 21); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 29); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 38); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 43); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 48).

[0190] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 22) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (ii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0191] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 43) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 48) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0192] In one embodiment, the antibody molecule comprises:

[0193] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 22) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0194] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 43) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 48) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0195] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 22); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 29); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 43); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 48).

[0196] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 19) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 28) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0197] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of the monoclonal antibody ATG-005 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of the monoclonal antibody ATG-005 (e.g., SEQ ID NO: 44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of the monoclonal antibody ATG-005 (e.g., SEQ ID NO: 49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0198] In one embodiment, the antibody molecule comprises:

[0199] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of the monoclonal antibody ATG-005 (e.g., SEQ ID NO: 19) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of the monoclonal antibody ATG-005 (e.g., SEQ ID NO: 28) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of the monoclonal antibody ATG-005 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0200] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0201] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 19); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 28); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 38); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 44); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 49).

[0202] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 20) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 28) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (ii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0203] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0204] In one embodiment, the antibody molecule comprises:

[0205] (i) VH, which comprises one, two or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:20) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:28) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:35) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology, and

[0206] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:38) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:44) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:49) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0207] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:20); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:28); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:44); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:49).

[0208] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:21) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:29) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:35) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0209] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0210] In one embodiment, the antibody molecule comprises:

[0211] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 21) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0212] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:38) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:44) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:49) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0213] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:21); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:29); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:38); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:44); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:49).

[0214] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 22) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (ii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0215] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0216] In one embodiment, the antibody molecule comprises:

[0217] (i) VH, which comprises one, two or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 22) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 29) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 35) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology, and

[0218] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 38) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 44) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 49) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0219] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:22); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:29); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:44); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:49).

[0220] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:22) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:29) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:35) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0221] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0222] In one embodiment, the antibody molecule comprises:

[0223] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 22) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0224] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0225] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:22); HCDR2, which comprises the amino acid sequence of HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:29); and HCDR3, which comprises the amino acid sequence of HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:38); LCDR2, which comprises the amino acid sequence of LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:44); and LCDR3, which comprises the amino acid sequence of LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:49).

[0226] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 20) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 28) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (ii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0227] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and wherein the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0228] In one embodiment, the antibody molecule comprises:

[0229] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 20) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 28) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0230] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0231] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:20); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:28); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:44); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:49).

[0232] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:54) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0233] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of the monoclonal antibody ATG-001 (e.g., SEQ ID NO: 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of the monoclonal antibody ATG-001 (e.g., SEQ ID NO: 76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of the monoclonal antibody ATG-001 (e.g., SEQ ID NO: 81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0234] In one embodiment, the antibody molecule comprises:

[0235] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of the monoclonal antibody ATG-001 (e.g., SEQ ID NO: 54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of the monoclonal antibody ATG-001 (e.g., SEQ ID NO: 59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of the monoclonal antibody ATG-001 (e.g., SEQ ID NO: 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0236] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0237] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:54); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:59); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:71); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:76); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:81).

[0238] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (ii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0239] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0240] In one embodiment, the antibody molecule comprises:

[0241] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0242] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0243] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:55); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:59); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:66), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:71); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:76); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:81).

[0244] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:54) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0245] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0246] In one embodiment, the antibody molecule comprises:

[0247] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0248] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0249] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:54); HCDR2, which comprises the amino acid sequence of HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:60); and HCDR3, which comprises the amino acid sequence of HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:71); LCDR2, which comprises the amino acid sequence of LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:76); and LCDR3, which comprises the amino acid sequence of LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:81).

[0250] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (ii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0251] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and wherein the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0252] In one embodiment, the antibody molecule comprises:

[0253] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0254] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0255] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:55); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:60); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:66), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:71); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:76); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:81).

[0256] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementary determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:54) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0257] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0258] In one embodiment, the antibody molecule comprises:

[0259] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0260] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:71) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:77) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:82) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology.

[0261] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:54); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:59); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:71); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:77); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:82).

[0262] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0263] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:77) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:82) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0264] In one embodiment, the antibody molecule comprises:

[0265] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0266] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0267] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:55); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:59); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:66), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:71); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:77); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:82).

[0268] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:54) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0269] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0270] In one embodiment, the antibody molecule comprises:

[0271] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0272] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 71) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 77) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 82) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0273] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 54); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 60); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 71); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 77); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 82).

[0274] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (ii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0275] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0276] In one embodiment, the antibody molecule comprises:

[0277] (i) VH, which comprises one, two or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:55) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:60) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:66) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology, and

[0278] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:71) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:77) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:82) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology.

[0279] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:55); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:60); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:66), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:71); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:77); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:82).

[0280] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and wherein the heavy chain variable region comprises one, two, or all of the following: (i) an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; (ii) an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or (ii) an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0281] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0282] In one embodiment, the antibody molecule comprises:

[0283] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0284] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:71) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:77) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:82) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0285] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:55); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:60); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:71); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:77); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:82).

[0286] In one embodiment, the antibody molecule comprises a VH, wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: (i) HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (ii) HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0287] In one embodiment, the antibody molecule comprises a VL, wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: (i) LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; (ii) LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or (iii) LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0288] In one embodiment, the antibody molecule comprises:

[0289] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0290] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0291] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:55); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:59); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:66), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:71); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:77); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:82).

[0292] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-001 (e.g., SEQ ID NO:1) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0293] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-001 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0294] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-001 (e.g., SEQ ID NO:1) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-001 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0295] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-001 (e.g., SEQ ID NO:1); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-001 (e.g., SEQ ID NO:10).

[0296] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-002 (e.g., SEQ ID NO:2) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0297] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-002 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0298] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-002 (e.g., SEQ ID NO:2) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-002 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0299] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-002 (e.g., SEQ ID NO:2); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-002 (e.g., SEQ ID NO:10).

[0300] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-003 (e.g., SEQ ID NO:3) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0301] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-003 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0302] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-003 (e.g., SEQ ID NO:3) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-003 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0303] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-003 (e.g., SEQ ID NO:3); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-003 (e.g., SEQ ID NO:10).

[0304] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-004 (e.g., SEQ ID NO:4) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0305] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-004 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence that is at least 85, 90, 95, 96, 97, 98, 99, or 100% homologous.

[0306] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-004 (e.g., SEQ ID NO:4) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence that is at least 85, 90, 95, 96, 97, 98, 99, or 100% homologous; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-004 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence that is at least 85, 90, 95, 96, 97, 98, 99, or 100% homologous.

[0307] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-004 (e.g., SEQ ID NO:4); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-004 (e.g., SEQ ID NO:10).

[0308] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-005 (e.g., SEQ ID NO:1) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence that is at least 85, 90, 95, 96, 97, 98, 99, or 100% homologous.

[0309] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-005 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence that is at least 85, 90, 95, 96, 97, 98, 99, or 100% homologous.

[0310] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-005 (e.g., SEQ ID NO:1) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-005 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0311] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-005 (e.g., SEQ ID NO:1); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-005 (e.g., SEQ ID NO:11).

[0312] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-006 (e.g., SEQ ID NO:2) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0313] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-006 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0314] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-006 (e.g., SEQ ID NO:2) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-006 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0315] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-006 (e.g., SEQ ID NO:2); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-006 (e.g., SEQ ID NO:11).

[0316] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-007 (e.g., SEQ ID NO:3) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0317] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-007 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0318] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-007 (e.g., SEQ ID NO:3) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence with at least 85, 90, 95, 96, 97, 98, 99, or 100% homology; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-007 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence with at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0319] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-007 (e.g., SEQ ID NO:3); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-007 (e.g., SEQ ID NO:11).

[0320] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-008 (e.g., SEQ ID NO:4) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence with at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0321] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-008 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence with at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0322] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-008 (e.g., SEQ ID NO:4) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-008 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0323] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-008 (e.g., SEQ ID NO:4); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-008 (e.g., SEQ ID NO:11).

[0324] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-012 (e.g., SEQ ID NO:4) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0325] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-012 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0326] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-012 (e.g., SEQ ID NO:4) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-012 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0327] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-012 (e.g., SEQ ID NO:4); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-012 (e.g., SEQ ID NO:11).

[0328] In one embodiment, the antibody molecule comprises a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-013 (e.g., SEQ ID NO:2) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0329] In one embodiment, the antibody molecule comprises a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-013 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0330] In one embodiment, the antibody molecule comprises: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-013 (e.g., SEQ ID NO:2) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homologous; and (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-013 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has an amino acid sequence that is at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homologous.

[0331] In one embodiment, the antibody molecule comprises: (i) a VH that comprises the amino acid sequence of the VH of monoclonal antibody ATG-013 (e.g., SEQ ID NO:2); and (ii) a VL that comprises the amino acid sequence of the VL of monoclonal antibody ATG-013 (e.g., SEQ ID NO:11).

[0332] In one embodiment, the antibody molecule is monoclonal antibody ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013.

[0333] In one embodiment, the antibody molecule comprises one or more framework regions derived from human framework germline sequences.

[0334] In one embodiment, the antibody molecule comprises the VH described in Table 1. In one embodiment, the antibody molecule comprises the VL described in Table 1. In one embodiment, the antibody molecule comprises the VH and VL described in Table 1. In one embodiment, the antibody molecule comprises one, two, or three CDRs of the VH described in Table 1. In one embodiment, the antibody molecule comprises one, two, or three CDRs of the VL described in Table 1. In one embodiment, the antibody molecule comprises one, two, or three CDRs of the VH described in Table 1 and one, two, or three CDRs of the VL described in Table 1.

[0335] In one embodiment, the antibody molecule comprises two VHs and two VLs. In one embodiment, the antibody molecule comprises an antigen-binding fragment. In one embodiment, the antibody molecule comprises Fab, F(ab')2, Fv, scFv, or Fd.

[0336] In one embodiment, the antibody molecule is an IgG antibody molecule, e.g., comprising a heavy chain constant region of IgG (e.g., IgG2 or IgG4) selected, for example, from IgG1, IgG2, IgG3 or IgG4. In one embodiment, the antibody molecule is an IgG1 antibody molecule, e.g., having the IgG1 constant region described herein. In another embodiment, the antibody molecule is an IgG2 antibody molecule, e.g., having the IgG2 constant region described herein. In one embodiment, the antibody molecule is an IgG3 antibody molecule, e.g., having the IgG3 constant region described herein. In another embodiment, the antibody molecule is an IgG4 antibody molecule, e.g., having the IgG4 constant region described herein. In another embodiment, the antibody molecule has a chimeric constant region comprising an IgG2, IgG3, and / or IgG4 isotype. In one embodiment, the heavy chain constant region comprises one or more amino acid modifications in the hinge, CH2 or CH3 region. In one embodiment, the antibody molecule comprises a light chain constant region of kappa or lambda light chain.

[0337] In one embodiment, the antibody molecule comprises an Fc region. In one embodiment, the Fc region comprises one or both of the Met-428-Leu and Asn-434-Ser substitutions at residues corresponding to methionine 428 and asparagine 434, respectively, according to EU numbering. In one embodiment, the Fc region comprises one, two, or three of the Met-252-Tyr, Ser-254-Thr, and Thr-256-Glu substitutions at residues corresponding to methionine 252, serine 254, and threonine 256, respectively, according to EU numbering.

[0338] In one aspect, the present disclosure provides an anti-C5 antibody molecule described herein, e.g., a synthetic or isolated anti-C5 antibody molecule described herein.

[0339] In one embodiment, the antibody molecule comprises:

[0340] (i) A variable heavy chain (VH), wherein the variable heavy chain comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the variable heavy chain comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 19 or 54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 28 or 59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0341] (ii) A variable light chain (VL), wherein the variable light chain comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the variable light chain comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 43 or 76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 48 or 81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0342] In one embodiment, the antibody molecule comprises:

[0343] (i) A variable heavy chain (VH), wherein the variable heavy chain comprises three heavy chain complementarity-determining regions (HCDR1, HCDR2, and HCDR3), and the variable heavy chain comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 20 or 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 28 or 59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0344] (ii) A variable light chain (VL), wherein the variable light chain comprises three light chain complementarity-determining regions (LCDR1, LCDR2, and LCDR3), and the variable light chain comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 43 or 76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO: 48 or 81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0345] In one embodiment, the antibody molecule comprises:

[0346] (i) A variable heavy chain (VH), wherein the variable heavy chain comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the variable heavy chain comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 21 or 54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 29 or 60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0347] (ii) A variable light chain (VL), wherein the variable light chain comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the variable light chain comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 43 or 76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 48 or 81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0348] In one embodiment, the antibody molecule comprises:

[0349] (i) A variable heavy chain (VH), wherein the variable heavy chain comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the variable heavy chain comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 22 or 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 29 or 60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0350] (ii) A variable light chain (VL), wherein the variable light chain comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the variable light chain comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 43 or 76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 48 or 81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0351] In one embodiment, the antibody molecule comprises:

[0352] (i) A variable heavy chain (VH), wherein the variable heavy chain comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the variable heavy chain comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 19 or 54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 28 or 59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0353] (ii) A variable light chain (VL), wherein the variable light chain comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the variable light chain comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 44 or 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO: 49 or 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0354] In one embodiment, the antibody molecule comprises:

[0355] (i) A heavy chain variable region (VH), wherein the heavy chain variable region contains three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region contains one, two, or all of the following: HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 20 or 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which contains an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 28 or 59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which contains an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0356] (ii) A light chain variable region (VL), wherein the light chain variable region contains three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region contains one, two, or all of the following: LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which contains an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 44 or 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which contains an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO: 49 or 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0357] In one embodiment, the antibody molecule comprises:

[0358] (i) A heavy chain variable region (VH), wherein the heavy chain variable region contains three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region contains one, two, or all of the following: HCDR1, which contains an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 21 or 54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which contains an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 29 or 60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which contains an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0359] (ii) A light chain variable region (VL), wherein the light chain variable region contains three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region contains one, two, or all of the following: LCDR1, which contains an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which contains an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 44 or 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which contains an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 49 or 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0360] In one embodiment, the antibody molecule comprises:

[0361] (i) A heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 22 or 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 29 or 60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0362] (ii) A light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 44 or 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 49 or 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0363] In one embodiment, the antibody molecule comprises:

[0364] (i) A variable heavy chain (VH), wherein the variable heavy chain comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the variable heavy chain comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 22 or 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 29 or 60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0365] (ii) A variable light chain (VL), wherein the variable light chain comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the variable light chain comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 44 or 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 49 or 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0366] In one embodiment, the antibody molecule comprises:

[0367] (i) A heavy chain variable region (VH), wherein the heavy chain variable region comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and the heavy chain variable region comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 20 or 55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 28 or 59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 35 or 66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0368] (ii) A light chain variable region (VL), wherein the light chain variable region comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), and the light chain variable region comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 38 or 71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 44 or 77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 49 or 82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0369] In one embodiment, the antibody molecule comprises:

[0370] (i) VH, which comprises one, two or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 19) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 28) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 35) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology, and

[0371] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 38) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 43) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO: 48) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0372] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:19); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:28); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:43); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:48).

[0373] In one embodiment, the antibody molecule comprises:

[0374] (i) a VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:20) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:28) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:35) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology, and

[0375] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:43) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:48) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0376] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:20); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:28); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:38); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:43); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:48).

[0377] In one embodiment, the antibody molecule comprises:

[0378] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 21) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0379] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 43) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 48) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0380] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 21); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 29); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 43); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO: 48).

[0381] In one embodiment, the antibody molecule comprises:

[0382] (i) a VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 22) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology, and

[0383] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 43) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 48) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0384] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 22); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 29); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 38); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 43); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO: 48).

[0385] In one embodiment, the antibody molecule comprises:

[0386] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:19) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:28) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0387] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0388] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:19); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:28); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:44); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:49).

[0389] In one embodiment, the antibody molecule comprises:

[0390] (i) a VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:20) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:28) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:35) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology, and

[0391] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:38) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:44) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:49) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0392] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:20); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:28); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:38); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:44); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:49).

[0393] In one embodiment, the antibody molecule comprises:

[0394] (i) VH, which comprises one, two or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 21) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 29) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 35) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology, and

[0395] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 38) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 44) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 49) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0396] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 21); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 29); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 44); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO: 49).

[0397] In one embodiment, the antibody molecule comprises:

[0398] (i) a VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 22) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0399] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:38) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:44) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:49) by no more than 1, 2 or 3 amino acid residues or has at least 85%, 90%, 95%, 99% or 100% homology.

[0400] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:22); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:29); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:38); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:44); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:49).

[0401] In one embodiment, the antibody molecule comprises:

[0402] (i) VH, which comprises one, two, or all of the following: HCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 22) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; HCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 29) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or HCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0403] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 38) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 44) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 49) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0404] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 22); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 29); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 35), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 38); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 44); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO: 49).

[0405] In one embodiment, the antibody molecule comprises:

[0406] (i) a VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 20) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 28) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 35) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology, and

[0407] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 38) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 44) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 49) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology.

[0408] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 20); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 28); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 35), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 38); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 44); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO: 49).

[0409] In one embodiment, the antibody molecule comprises:

[0410] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0411] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0412] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:54); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:59); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:66), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:71); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:76); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-001 (e.g., SEQ ID NO:81).

[0413] In one embodiment, the antibody molecule comprises:

[0414] (i) a VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology, and

[0415] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:76) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:81) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology.

[0416] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:55); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:59); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:71); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:76); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-002 (e.g., SEQ ID NO:81).

[0417] In one embodiment, the antibody molecule comprises:

[0418] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0419] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0420] In one embodiment, the antibody molecule comprises: (i) a VH which comprises: an HCDR1 which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:54); an HCDR2 which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:60); and an HCDR3 which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:66), and (ii) a VL which comprises: an LCDR1 which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:71); an LCDR2 which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:76); and an LCDR3 which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-003 (e.g., SEQ ID NO:81).

[0421] In one embodiment, the antibody molecule comprises:

[0422] (i) a VH which comprises one, two or all of the following: an HCDR1 which comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:55) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; an HCDR2 which comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:60) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; or an HCDR3 which comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:66) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology, and

[0423] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:76) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:81) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0424] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:55); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:60); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:71); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:76); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-004 (e.g., SEQ ID NO:81).

[0425] In one embodiment, the antibody molecule comprises:

[0426] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0427] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0428] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:54); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:59); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:66), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:71); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:77); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-005 (e.g., SEQ ID NO:82).

[0429] In one embodiment, the antibody molecule comprises:

[0430] (i) a VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0431] (ii) VL, which comprises one, two or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:71) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:77) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:82) by no more than 1, 2 or 3 amino acid residues or has at least 85, 90, 95, 99 or 100% homology.

[0432] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of HCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:55); HCDR2, which comprises the amino acid sequence of HCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:59); and HCDR3, which comprises the amino acid sequence of HCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of LCDR1 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:71); LCDR2, which comprises the amino acid sequence of LCDR2 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:77); and LCDR3, which comprises the amino acid sequence of LCDR3 of monoclonal antibody ATG-006 (e.g., SEQ ID NO:82).

[0433] In one embodiment, the antibody molecule comprises:

[0434] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:54) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0435] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0436] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:54); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:60); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:66), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:71); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:77); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-007 (e.g., SEQ ID NO:82).

[0437] In one embodiment, the antibody molecule comprises:

[0438] (i) a VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology, and

[0439] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0440] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:55); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:60); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:71); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:77); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-008 (e.g., SEQ ID NO:82).

[0441] In one embodiment, the antibody molecule comprises:

[0442] (i) A VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:60) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology, and

[0443] (ii) A VL that comprises one, two, or all of the following: an LCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; an LCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or an LCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0444] In one embodiment, the antibody molecule comprises: (i) a VH that comprises: an HCDR1 that comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:55); an HCDR2 that comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:60); and an HCDR3 that comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:66), and (ii) a VL that comprises: an LCDR1 that comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:71); an LCDR2 that comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:77); and an LCDR3 that comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-012 (e.g., SEQ ID NO:82).

[0445] In one embodiment, the antibody molecule comprises:

[0446] (i) a VH that comprises one, two, or all of the following: an HCDR1 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:55) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; an HCDR2 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:59) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology; or an HCDR3 that comprises an amino acid sequence that differs from the amino acid sequence of the HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:66) by no more than 1, 2, or 3 amino acid residues or has at least 85, 90, 95, 99, or 100% homology, and

[0447] (ii) VL, which comprises one, two, or all of the following: LCDR1, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:71) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; LCDR2, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:77) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology; or LCDR3, which comprises an amino acid sequence that differs from the amino acid sequence of the LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:82) by no more than 1, 2, or 3 amino acid residues or has at least 85%, 90%, 95%, 99%, or 100% homology.

[0448] In one embodiment, the antibody molecule comprises: (i) VH, which comprises: HCDR1, which comprises the amino acid sequence of the HCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:55); HCDR2, which comprises the amino acid sequence of the HCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:59); and HCDR3, which comprises the amino acid sequence of the HCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:66), and (ii) VL, which comprises: LCDR1, which comprises the amino acid sequence of the LCDR1 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:71); LCDR2, which comprises the amino acid sequence of the LCDR2 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:77); and LCDR3, which comprises the amino acid sequence of the LCDR3 of monoclonal antibody ATG-013 (e.g., SEQ ID NO:82).

[0449] In one embodiment, the antibody molecule comprises one or two of the following: (i) VH, which comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-001 (e.g., SEQ ID NO:1) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology; or (ii) VL, which comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-001 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0450] In one embodiment, the antibody molecule comprises one or both of the following: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-002 (e.g., SEQ ID NO:2) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology; or (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-002 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0451] In one embodiment, the antibody molecule comprises one or both of the following: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-003 (e.g., SEQ ID NO:3) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology; or (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-003 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0452] In one embodiment, the antibody molecule comprises one or both of the following: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-004 (e.g., SEQ ID NO:4) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology; or (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-004 (e.g., SEQ ID NO:10) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85, 90, 95, 96, 97, 98, 99, or 100% homology.

[0453] In one embodiment, the antibody molecule comprises one or both of the following: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-005 (e.g., SEQ ID NO:1) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology; or (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-005 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0454] In one embodiment, the antibody molecule comprises one or both of the following: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-006 (e.g., SEQ ID NO:2) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology; or (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-006 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0455] In one embodiment, the antibody molecule comprises one or both of the following: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-007 (e.g., SEQ ID NO:3) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology; or (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-007 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0456] In one embodiment, the antibody molecule comprises one or both of the following: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-008 (e.g., SEQ ID NO:4) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology; or (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-008 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0457] In one embodiment, the antibody molecule comprises one or both of the following: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-012 (e.g., SEQ ID NO:4) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology; or (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-012 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0458] In one embodiment, the antibody molecule comprises one or both of the following: (i) a VH that comprises an amino acid sequence that differs from the amino acid sequence of the VH of monoclonal antibody ATG-013 (e.g., SEQ ID NO:2) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology; or (ii) a VL that comprises an amino acid sequence that differs from the amino acid sequence of the VL of monoclonal antibody ATG-013 (e.g., SEQ ID NO:11) by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues or has at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology.

[0459] In one embodiment, the antibody molecule comprises a VH encoded by the nucleotide sequence of SEQ ID NO: 100 (or a nucleotide sequence substantially identical thereto), or a VL encoded by the nucleotide sequence of SEQ ID NO: 101 (or a nucleotide sequence substantially identical thereto), or both. In one embodiment, the antibody molecule comprises a VH encoded by the nucleotide sequence of SEQ ID NO: 102 (or a nucleotide sequence substantially identical thereto), or a VL encoded by the nucleotide sequence of SEQ ID NO: 103 (or a nucleotide sequence substantially identical thereto), or both. In one embodiment, the antibody molecule comprises a VH encoded by the nucleotide sequence of SEQ ID NO: 104 (or a nucleotide sequence substantially identical thereto), or a VL encoded by the nucleotide sequence of SEQ ID NO: 105 (or a nucleotide sequence substantially identical thereto), or both. In one embodiment, the antibody molecule comprises a VH encoded by the nucleotide sequence of SEQ ID NO: 106 (or a nucleotide sequence substantially identical thereto), or a VL encoded by the nucleotide sequence of SEQ ID NO: 107 (or a nucleotide sequence substantially identical thereto), or both. In one embodiment, the antibody molecule comprises a VH encoded by the nucleotide sequence of SEQ ID NO: 108 (or a nucleotide sequence substantially identical thereto), or a VL encoded by the nucleotide sequence of SEQ ID NO: 109 (or a nucleotide sequence substantially identical thereto), or both. In one embodiment, the antibody molecule comprises a VH encoded by the nucleotide sequence of SEQ ID NO: 110 (or a nucleotide sequence substantially identical thereto), or a VL encoded by the nucleotide sequence of SEQ ID NO: 111 (or a nucleotide sequence substantially identical thereto), or both. In one embodiment, the antibody molecule comprises a VH encoded by the nucleotide sequence of SEQ ID NO: 112 (or a nucleotide sequence substantially identical thereto), or a VL encoded by the nucleotide sequence of SEQ ID NO: 113 (or a nucleotide sequence substantially identical thereto), or both. In one embodiment, the antibody molecule comprises a VH encoded by the nucleotide sequence of SEQ ID NO: 114 (or a nucleotide sequence substantially identical thereto), or a VL encoded by the nucleotide sequence of SEQ ID NO: 115 (or a nucleotide sequence substantially identical thereto), or both.

[0460] In one embodiment, the antibody molecule is monoclonal antibody ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013. In one embodiment, the antibody molecule comprises a VH comprising the amino acid sequence of any one of SEQ ID NO: 1-9, a VL comprising the amino acid sequence of any one of SEQ ID NO: 10-15, or both.

[0461] In one embodiment, the antibody molecule is any one of antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013.

[0462] In one embodiment, the antibody molecule is a synthetic antibody molecule. In one embodiment, the antibody molecule is an isolated antibody molecule. In one embodiment, the antibody molecule is a recombinant antibody molecule. In one embodiment, the antibody molecule is a humanized antibody. In one embodiment, the antibody molecule is a monospecific antibody molecule. In one embodiment, the antibody molecule is a multispecific antibody molecule.

[0463] In one embodiment, the antibody molecule comprises two heavy chain variable regions and two light chain variable regions. In one embodiment, the antibody molecule comprises an antigen-binding fragment. In one embodiment, the antibody molecule comprises Fab, F(ab')2, Fv, scFv or Fd.

[0464] In one embodiment, the antibody molecule is an IgG antibody molecule, for example comprising a heavy chain constant region of IgG (such as IgG2 or IgG4) selected from IgG1, IgG2, IgG3 or IgG4. In one embodiment, the antibody molecule is an IgG1 antibody molecule, for example having the IgG1 constant region described herein. In another embodiment, the antibody molecule is an IgG2 antibody molecule, for example having the IgG2 constant region described herein. In one embodiment, the antibody molecule is an IgG3 antibody molecule, for example having the IgG3 constant region described herein. In another embodiment, the antibody molecule is an IgG4 antibody molecule, for example having the IgG4 constant region described herein. In another embodiment, the antibody molecule has a chimeric constant region comprising IgG2, IgG3 and / or IgG4 isotypes. In one embodiment, the heavy chain constant region comprises one or more amino acid modifications in the hinge, CH2 or CH3 region. In one embodiment, the antibody molecule comprises a light chain constant region of κ or λ light chain.

[0465] In one embodiment, the antibody molecule comprises an Fc region. In one embodiment, the Fc region comprises one or more mutations. In one embodiment, the Fc region comprises Met-428-Leu and Asn-434-Ser substitutions at residues corresponding to methionine 428 and asparagine 434, respectively, according to EU numbering. In one embodiment, the Fc region comprises one, two, or three of Met-252-Tyr, Ser-254-Thr, and Thr-256-Glu substitutions at residues corresponding to methionine 252, serine 254, and threonine 256, respectively, according to EU numbering.

[0466] In one aspect, the present disclosure provides an antibody molecule that:

[0467] a) competes with an anti-C5 antibody molecule for binding to C5, the anti-C5 antibody molecule comprising heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) of any one of, for example, the monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013 described in Table 1; or

[0468] b) combined with or substantially combined with an epitope that completely or partially overlaps with the epitope of an anti-C5 antibody molecule, said anti-C5 antibody molecule comprising, for example, the monoclonal antibody ATG-001 described in Table 1 (e.g., SEQ ID NO: 19, 28, 35, 38, 43, and / or 48 respectively according to the Chothia numbering, or SEQ ID NO: 54, 59, 66, 71, 76, and / or 81 respectively according to the Kabat numbering), ATG-002 (e.g., SEQ ID NO: 20, 28, 35, 38, 43, and / or 48 respectively according to the Chothia numbering, or SEQ ID NO: 55, 59, 66, 71, 76, and / or 81 respectively according to the Kabat numbering), ATG-003 (e.g., SEQ ID NO: 21, 29, 35, 38, 43, and / or 48 respectively according to the Chothia numbering, or SEQ ID NO: 54, 60, 66, 71, 76, and / or 81 respectively according to the Kabat numbering), ATG-004 (e.g., SEQ ID NO: 22, 29, 35, 38, 43, and / or 48 respectively according to the Chothia numbering, or SEQ ID NO: 55, 60, 66, 71, 76, and / or 81 respectively according to the Kabat numbering), ATG-005 (e.g., SEQ ID NO: 19, 28, 35, 38, 44, and / or 49 respectively according to the Chothia numbering, or SEQ ID NO: 54, 59, 66, 71, 77, and / or 82 respectively according to the Kabat numbering), ATG-006 (e.g., SEQ ID NO: 20, 28, 35, 38, 44, and / or 49 respectively according to the Chothia numbering, or SEQ ID NO: 55, 59, 66, 71, 77, and / or 82 respectively according to the Kabat numbering), ATG-007 (e.g., SEQ ID NO: 21, 29, 35, 38, 44, and / or 49 respectively according to the Chothia numbering, or SEQ ID NO: 54, 60, 66, 71, 77, and / or 82 respectively according to the Kabat numbering), ATG-008 (e.g., SEQ ID NO: 22, 29, 35, 38, 44, and / or 49 respectively according to the Chothia numbering, or SEQ ID NO: 55, 60, 66, 71, 77, and / or 82 respectively according to the Kabat numbering), ATG-012 (e.g., SEQ ID NO: 22, 29, 35, 38, 44, and / or 49 respectively according to the Chothia numbering, or SEQ ID NO: 55, 60, 66, 71, 77, and / or 82 respectively according to the Kabat numbering) or ATG-013 (e.g., SEQ ID NO: 20, 28, 35, 38, 44, and / or 49,The heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3) according to the Chothia numbering, or SEQ ID NO:55, 59, 66, 71, 77, and / or 82 respectively, according to the Kabat numbering).

[0469] In one embodiment, the antibody molecule competes for binding with an anti-C5 antibody molecule comprising the VH and VL of any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013.

[0470] In one embodiment, the antibody molecule binds or substantially binds to an epitope that completely or partially overlaps with the epitope of an anti-C5 antibody molecule comprising the VH and VL of any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013.

[0471] In one embodiment, the antibody molecule is a synthetic antibody molecule. In one embodiment, the antibody molecule is an isolated antibody molecule. In one embodiment, the antibody molecule is a recombinant antibody molecule. In one embodiment, the antibody molecule is a humanized antibody. In one embodiment, the antibody molecule is a monospecific antibody molecule. In one embodiment, the antibody molecule is a multispecific antibody molecule.

[0472] In one embodiment, the antibody molecule competes for binding with two, three, four, five, six, seven, or all of the anti-C5 antibody molecules comprising the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013.

[0473] In one embodiment, the antibody molecule competes for binding with two, three, four, five, six, seven, or all of the anti-C5 antibody molecules comprising the VH and VL of any one of monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012, or ATG-013.

[0474] In one embodiment, the antibody molecule binds or substantially binds to an epitope that is fully or partially overlapping with the epitopes of two, three, four, five, six, seven or all of the anti-C5 antibody molecules, and the anti-C5 antibody molecules comprise the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of any one of the monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013.

[0475] In one embodiment, the antibody molecule binds or substantially binds to an epitope that is fully or partially overlapping with the epitopes of two, three, four, five, six, seven or all of the anti-C5 antibody molecules, and the anti-C5 antibody molecules comprise the VH and VL of any one of the monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013.

[0476] In one embodiment, the antibody molecule binds or substantially binds to an epitope that is fully or partially overlapping with the epitopes of two, three, four, five, six, seven or all of the antibody molecules, and the antibody molecules comprise the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of any one of the monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013.

[0477] In one embodiment, the antibody molecule comprises the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of any one of the monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013.

[0478] In one embodiment, the antibody molecule binds or substantially binds to an epitope that is fully or partially overlapping with the epitopes of two, three, four, five, six, seven or all of the antibody molecules, and the antibody molecules comprise the VH and VL of any one of the monoclonal antibodies ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 or ATG-013.

[0479] In one embodiment, the antibody molecule is a synthetic antibody molecule. In one embodiment, the antibody molecule is an isolated antibody molecule. In one embodiment, the antibody molecule is a recombinant antibody molecule. In one embodiment, the antibody molecule is a humanized antibody. In one embodiment, the antibody molecule is a monospecific antibody molecule. In one embodiment, the antibody molecule is a multispecific antibody molecule.

[0480] In one embodiment, the antibody molecule comprises two heavy chain variable regions and two light chain variable regions. In one embodiment, the antibody molecule comprises an antigen-binding fragment. In one embodiment, the antibody molecule comprises Fab, F(ab')2, Fv, scFv or Fd.

[0481] In one embodiment, the antibody molecule is an IgG antibody molecule, for example comprising a heavy chain constant region of IgG (such as IgG2 or IgG4) selected from, for example, IgG1, IgG2, IgG3 or IgG4. In one embodiment, the antibody molecule is an IgG1 antibody molecule, for example having an IgG1 constant region as described herein. In another embodiment, the antibody molecule is an IgG2 antibody molecule, for example having an IgG2 constant region as described herein. In one embodiment, the antibody molecule is an IgG3 antibody molecule, for example having an IgG3 constant region as described herein. In another embodiment, the antibody molecule is an IgG4 antibody molecule, for example having an IgG4 constant region as described herein. In another embodiment, the antibody molecule has a chimeric constant region comprising IgG2, IgG3 and / or IgG4 isotypes. In one embodiment, the heavy chain constant region comprises one or more amino acid modifications in the hinge, CH2 or CH3 region. In one embodiment, the antibody molecule comprises a light chain constant region of κ or λ light chain.

[0482] In one embodiment, the antibody molecule comprises an Fc region. In one embodiment, the Fc region comprises one or more mutations. In one embodiment, the Fc region comprises Met-428-Leu and Asn-434-Ser substitutions at residues corresponding to methionine 428 and asparagine 434, respectively, according to EU numbering. In one embodiment, the Fc region comprises one, two or three of Met-252-Tyr, Ser-254-Thr and Thr-256-Glu substitutions at residues corresponding to methionine 252, serine 254 and threonine 256, respectively, according to EU numbering.

[0483] In one aspect, the present disclosure provides a composition, such as a pharmaceutical composition, comprising the antibody molecule as described herein. In one embodiment, the composition further comprises a pharmaceutically acceptable carrier.

[0484] In one aspect, the present disclosure provides a nucleic acid molecule encoding the heavy chain variable region (VH), the light chain variable region (VL), or both of the antibody molecules described herein.

[0485] In one aspect, the present disclosure provides a vector comprising the nucleic acid molecule described herein.

[0486] In one aspect, the present disclosure provides a cell, such as an isolated cell, comprising the nucleic acid molecule described herein or the vector described herein.

[0487] In one aspect, the present disclosure provides a kit comprising the antibody molecules described herein and instructions for use of the antibody molecules.

[0488] In one aspect, the present disclosure provides a container comprising the antibody molecules described herein.

[0489] In one aspect, the present disclosure provides a method for preparing an anti-C5 antibody molecule, the method comprising culturing the cell described herein under conditions that permit the production of the antibody molecule, thereby producing the antibody molecule.

[0490] In one embodiment, the method further comprises isolating the antibody molecule.

[0491] In one aspect, the present disclosure provides a method for treating a complement-related disorder (such as the complement-related disorders described herein), the method comprising administering to an individual in need thereof an effective amount of the antibody molecule described herein or the composition described herein, thereby treating the complement-related disorder.

[0492] In one embodiment, the complement-related disorder is inflammation. In one embodiment, the complement-related disorder is selected from the group consisting of ischemia-reperfusion injury, atypical hemolytic uremic syndrome (aHUS), typical or infectious hemolytic uremic syndrome (tHUS), dense deposit disease (DDD), paroxysmal nocturnal hemoglobinuria (PNH), neuromyelitis optica (NMO), macular degeneration, thrombotic thrombocytopenic purpura (TTP), myasthenia gravis, cold agglutinin disease, Guillain-Barre Syndrome, Degos'disease, transplant rejection, sepsis, glomerulonephritis, and thrombotic microangiopathy (TMA). In one embodiment, the complement-related disorder is PNH. In one embodiment, the complement-related disorder is aHUS.

[0493] In one embodiment, the individual is human. In one embodiment, the antibody molecule is administered intravenously to the individual.

[0494] In one embodiment, an antibody molecule is administered to an individual at a dose between 0.1 mg / kg and 50 mg / kg, such as between 0.2 mg / kg and 25 mg / kg, between 0.5 mg / kg and 10 mg / kg, between 0.5 mg / kg and 5 mg / kg, between 0.5 mg / kg and 3 mg / kg, between 0.5 mg / kg and 2.5 mg / kg, between 0.5 mg / kg and 2 mg / kg, between 0.5 mg / kg and 1.5 mg / kg, between 0.5 mg / kg and 1 mg / kg, between 1 mg / kg and 1.5 mg / kg, between 1 mg / kg and 2 mg / kg, between 1 mg / kg and 2.5 mg / kg, between 1 mg / kg and 3 mg / kg, between 1 mg / kg and 2.5 mg / kg, or between 1 mg / kg and 5 mg / kg.

[0495] In one embodiment, an antibody molecule is administered to an individual at a fixed dose between 10 mg and 1000 mg, such as between 10 mg and 500 mg, between 10 mg and 250 mg, between 10 mg and 150 mg, between 10 mg and 100 mg, between 10 mg and 50 mg, between 250 mg and 500 mg, between 150 mg and 500 mg, between 100 mg and 500 mg, between 50 mg and 500 mg, between 25 mg and 250 mg, between 50 mg and 150 mg, between 50 mg and 100 mg, between 100 mg and 150 mg, between 100 mg and 200 mg, or between 150 mg and 250 mg.

[0496] In one embodiment, the antibody molecule is administered once a week, twice a week, once every two weeks, once every three weeks, once every four weeks, once every eight weeks, once a month, once every two months, or once every three months.

[0497] In one embodiment, administration of the antibody molecule can reduce the activity of C5 in a tissue (such as blood or blood cells (such as red blood cells)).

[0498] In one embodiment, the method further comprises administering to the individual a second therapy for a complement-related disorder.

[0499] In one aspect, the present disclosure provides a method for reducing the activity of C5 in a cell or an individual, the method comprising contacting the cell or the individual with an antibody molecule described herein or a composition described herein, or administering to an individual in need an effective amount of an antibody molecule described herein or a composition described herein, thereby reducing the activity of C5.

[0500] In one embodiment, the cell is a human cell. In one embodiment, the individual is human.

[0501] In one embodiment, the contacting step is performed in vitro, ex vivo or in vivo. In one embodiment, the antibody molecule is administered intravenously to the individual.

[0502] In one embodiment, the antibody molecule is administered to the individual at a dose between 0.1 mg / kg and 50 mg / kg, such as between 0.2 mg / kg and 25 mg / kg, between 0.5 mg / kg and 10 mg / kg, between 0.5 mg / kg and 5 mg / kg, between 0.5 mg / kg and 3 mg / kg, between 0.5 mg / kg and 2.5 mg / kg, between 0.5 mg / kg and 2 mg / kg, between 0.5 mg / kg and 1.5 mg / kg, between 0.5 mg / kg and 1 mg / kg, between 1 mg / kg and 1.5 mg / kg, between 1 mg / kg and 2 mg / kg, between 1 mg / kg and 2.5 mg / kg, between 1 mg / kg and 3 mg / kg, between 1 mg / kg and 2.5 mg / kg or between 1 mg / kg and 5 mg / kg.

[0503] In one embodiment, the antibody molecule is administered to the individual at a fixed dose between 10 mg and 1000 mg, such as between 10 mg and 500 mg, between 10 mg and 250 mg, between 10 mg and 150 mg, between 10 mg and 100 mg, between 10 mg and 50 mg, between 250 mg and 500 mg, between 150 mg and 500 mg, between 100 mg and 500 mg, between 50 mg and 500 mg, between 25 mg and 250 mg, between 50 mg and 150 mg, between 50 mg and 100 mg, between 100 mg and 150 mg, between 100 mg and 200 mg or between 150 mg and 250 mg.

[0504] In one embodiment, the antibody molecule is administered once a week, twice a week, once every two weeks, once every three weeks, once every four weeks, once every eight weeks, once a month, once every two months, once every three months.

[0505] In one embodiment, administering the antibody molecule can reduce the activity of C5 in a tissue (such as blood or blood cells (such as red blood cells)).

[0506] In one aspect, the present disclosure provides the use of an antibody molecule described herein or a composition described herein for treating a condition described herein or for manufacturing a medicament for treating a condition described herein.

[0507] In another aspect, the present disclosure provides the antibody molecules or the compositions described herein for treating the disorders described herein.

[0508] In one aspect, the present disclosure provides a method for detecting a C5 molecule, the method comprising contacting a cell or a sample from an individual with the antibody molecule described herein, thereby detecting the C5 molecule.

[0509] In one embodiment, the antibody molecule is conjugated to a detectable label. In one embodiment, the C5 molecule is detected in vitro or ex vivo. In another embodiment, the C5 molecule is detected in vivo.

[0510] The present disclosure encompasses all combinations of any one or more of the foregoing aspects and / or embodiments, as well as combinations with any one or more of the embodiments and examples set forth in the detailed description.

[0511] Other features, objects, and advantages of the compositions and methods herein will be apparent from the description, the drawings, and the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0512] Figures 1A - 1B A series of diagrams that show the evaluation of the purity and integrity of the indicated exemplary anti-C5 monoclonal antibodies using SDS-PAGE under non-reducing or reducing conditions and Figure 1A size-exclusion chromatography (SEC). ATG-001, ATG-002, ATG-003, ATG-005, ATG-006, ATG-007 contain their respective VH and VL sequences as listed in Table 1 and the IgG-1 heavy chain constant region sequence; ATG-004 and ATG-008 contain their respective VH and VL sequences as listed in Table 1 and the IgG2 / 4-LS heavy chain constant region sequence; and ATG-012 and ATG-013 contain their respective VH and VL sequences as listed in Table 1 and the IgG2 / 4-YTE heavy chain constant region sequence. Figure 1B

[0513] Figures 2A - 2B A series of diagrams showing the functional evaluation of engineered anti-C5 monoclonal antibodies. Figure 2A Showing the binding of the indicated exemplary anti-C5 monoclonal antibodies to human C5. Figure 2B ​Demonstration of the inhibition of cRBC hemolysis by the indicated exemplary anti-C5 monoclonal antibodies. ATG-001, ATG-002, ATG-003, ATG-005, ATG-006, ATG-007 comprise their respective VH and VL sequences as listed in Table 1 and an IgG-1 heavy chain constant region sequence; ATG-004 and ATG-008 comprise their respective VH and VL sequences as listed in Table 1 and an IgG2 / 4-LS heavy chain constant region sequence; and ATG-012 comprises their respective VH and VL sequences as listed in Table 1 and an IgG2 / 4-YTE heavy chain constant region sequence. Detailed Description

[0514] Antibody molecules are disclosed herein that bind to C5, such as human C5, with high affinity and specificity. Advantageously, several of the antibody molecules described herein have an improved ability to reduce (e.g., inhibit, block, or neutralize) one or more biological activities of C5. Also provided are nucleic acid molecules, expression vectors, host cells, compositions (e.g., pharmaceutical compositions), kits, and methods for preparing the antibody molecules. The antibody molecules and pharmaceutical compositions disclosed herein can be used (alone or in combination with other agents or treatment modalities) to treat, prevent, and / or diagnose disorders and conditions, such as disorders and conditions associated with the activation of C5.

[0515] Definitions

[0516] As used herein, the article “a / an” refers to one or more than one (e.g., at least one) grammatical object of the article.

[0517] Unless the context clearly indicates otherwise, the term “or” is used herein to mean the term “and / or” and can be used interchangeably therewith.

[0518] “About” and “substantially” generally should mean an acceptable degree of error for the quantity being measured in view of the nature or precision of the measurement. Exemplary degrees of error are within 20 percent (%) of the given value or value range, typically within 10%, and more typically within 5% (e.g., within 4%, 3%, 2%, or 1%).

[0519] The compositions and methods disclosed herein encompass sequences having a specified sequence or sequences that are substantially identical or similar thereto, such as sequences having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or greater identity to the specified sequence.

[0520] In the case of amino acid sequences, the term "substantially identical" is used herein to refer to a first amino acid having a sufficient or minimum number of amino acid residues that satisfy the following conditions: a) being identical to the aligned amino acid residue in a second amino acid sequence, or b) being a conservative substitution of the aligned amino acid residue in the second amino acid sequence, such that the first and second amino acid sequences may have a common domain and / or a common functional activity. For example, an amino acid sequence having a common domain and having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a reference sequence (such as the sequences provided herein).

[0521] In the case of nucleotide sequences, the term "substantially identical" is used herein to refer to a first nucleic acid sequence having a sufficient or minimum number of nucleotides that are identical to the aligned nucleotides in a second nucleic acid sequence, such that the first and second nucleotide sequences encode polypeptides having a common functional activity, or encode a common structural polypeptide domain or a common functional polypeptide activity. For example, a nucleotide sequence having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a reference sequence (such as the sequences provided herein).

[0522] The term "functional variant" refers to a polypeptide having an amino acid sequence that is substantially identical to a naturally occurring sequence, or encoded by a substantially identical nucleotide sequence, and that may have one or more activities of the naturally occurring sequence.

[0523] Homology or sequence identity between sequences is calculated as follows (the terms are used interchangeably herein).

[0524] To determine the percentage identity between two amino acid sequences or two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps may be introduced into one or both of the first and second amino acid or nucleic acid sequences for optimal alignment and, for comparison purposes, non-homologous sequences may be ignored). In a typical embodiment, the length of the reference sequence aligned for comparison purposes is at least 30% of the length of the reference sequence, such as at least 40%, 50%, 60%, 70%, 80%, 90% or 100%. The amino acid residues or nucleotides at the corresponding amino acid positions or nucleotide positions are then compared. If the position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position.

[0525] The percentage identity between two sequences is related to the number of identical positions shared by the sequences and takes into account the number of gaps and the length of each gap that need to be introduced for optimal alignment of the two sequences.

[0526] The comparison of sequences and the determination of the percentage identity between two sequences can be implemented using mathematical algorithms. In one embodiment, the Clustal Omega (Sievers et al., Mol Syst Biol. 2011;7:539) is used to determine the percentage identity between two amino acid or nucleotide sequences. In one embodiment, the Kalign2 (Lassmann et al., Nucleic Acids Res. 2009;37(3):858-65; Lassmann and Sonnhammer, BMC Bioinformatics. 2005;6:298) is used to determine the percentage identity between two amino acid or nucleotide sequences. In one embodiment, the MAFFT (Katoh and Standley, Mol Biol Evol. 2013;30(4):772-80) is used to determine the percentage identity between two amino acid or nucleotide sequences. In one embodiment, the MUSCLE (Edgar, Nucleic Acids Res. 2004;32(5):1792-7; Edgar, BMC Bioinformatics. 2004;5:113) is used to determine the percentage identity between two amino acid or nucleotide sequences. In one embodiment, the MView (Brown et al., Bioinformatics. 1998;14(4):380-1) is used to determine the percentage identity between two amino acid or nucleotide sequences. Other methods for determining the percentage identity between two sequences are also described, for example, in Li et al., Nucleic Acids Res. 2015;43(W1):W580-4; McWilliam et al., Nucleic Acids Res. 2013;41(Web Server issue):W597-600.

[0527] In one embodiment, the percent identity between two amino acid sequences is determined using the Needleman and Wunsch (J Mol Biol. 1970;48(3):443-53) algorithm, which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com), using the Blossum 62 matrix or PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. In one embodiment, the percent identity between two nucleotide sequences is determined using NWSgapdna, using the GAP program in the GCG software package (available at www.gcg.com). The CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. A suitable set of parameters (and the ones used, unless otherwise stated) is the Blossum 62 scoring matrix, which uses a gap penalty of 12, a gap extension penalty of 4, and a frameshift gap penalty of 5.

[0528] The percent identity between two amino acid or nucleotide sequences can be determined using the algorithm of Meyers and Miller (Comput Appl Biosci. 1988;4(1):11-7), which has been incorporated into the ALIGN program (version 2.0), using the PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4.

[0529] The nucleic acid and protein sequences described herein can be used as "query sequences" to search against public databases, for example, to identify other family members or related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul et al., 1990; J. Mol. Biol. 215:403-10. The BLAST nucleotide search can be performed using the NBLAST program, score = 100, wordlength = 12, to obtain nucleotide sequences homologous to the nucleic acids described herein. The BLAST protein search can be performed using the XBLAST program, score = 50, wordlength = 3, to obtain amino acid sequences homologous to the protein molecules described herein. To achieve gapped alignments for comparison purposes, gapped BLAST can be used as described in Altschul et al., Nucleic Acids Res. 1997;25:3389-3402. When using the BLAST and gapped BLAST programs, the default parameters of the corresponding programs (e.g., XBLAST and NBLAST) can be used. See www.ncbi.nlm.nih.gov.

[0530] As used herein, the term "hybridizing under low stringency, medium stringency, high stringency or very high stringency conditions" describes hybridization and wash conditions. Guidance for performing hybridization reactions can be found in Current Protocols in Molecular Biology, John Wiley & Sons, N.Y. (1989), Sections 6.3.1-6.3.6, which are incorporated by reference. The references describe both aqueous and non-aqueous methods and either can be used. The specific hybridization conditions referred to herein are as follows: 1) Low stringency hybridization conditions are in 6X sodium chloride / sodium citrate (SSC) at about 45°C, followed by washing twice in 0.2X SSC, 0.1% SDS at at least 50°C (for low stringency conditions, the wash temperature can be increased to 55°C); 2) Medium stringency hybridization conditions are in 6X SSC at about 45°C, followed by washing one or more times in 0.2X SSC, 0.1% SDS at 60°C; 3) High stringency hybridization conditions are in 6X SSC at about 45°C, followed by washing one or more times in 0.2X SSC, 0.1% SDS at 65°C; and preferably, 4) Very high stringency hybridization conditions are in 0.5M sodium phosphate, 7% SDS at 65°C, followed by washing one or more times in 0.2X SSC, 1% SDS at 65°C. Unless otherwise stated, very high stringency condition 4) is the appropriate condition and the condition that should be used.

[0531] It is understood that the molecules described herein may have other conservative or non-essential amino acid substitutions that do not significantly affect their function.

[0532] The term "amino acid" is intended to encompass all molecules, whether natural or synthetic, that include both an amino functional group and an acid functional group and are capable of being incorporated into a polymer of naturally occurring amino acids. Exemplary amino acids include naturally occurring amino acids; their analogs, derivatives and homologs; amino acid analogs having variant side chains; and all stereoisomers of any of the foregoing. As used herein, the term "amino acid" includes D- or L-optical isomers and peptidomimetics.

[0533] "Conservative amino acid substitution" is a substitution in which an amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids having basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), β-branched side chains (e.g., threonine, valine, isoleucine), and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine).

[0534] The terms "polypeptide", "peptide" and "protein" (if single-stranded) are used interchangeably herein to refer to a polymer of amino acids of any length. The polymer may be linear or branched, it may contain modified amino acids, and it may be interspersed with non-amino acids. The terms also encompass amino acid polymers that have been modified; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component. A polypeptide may be isolated from a natural source, produced by recombinant techniques from a eukaryotic or prokaryotic host, or be the product of a synthetic procedure.

[0535] The terms "nucleic acid", "nucleic acid sequence", "nucleotide sequence" or "polynucleotide sequence" and "polynucleotide" are used interchangeably. It refers to a polymeric form of nucleotides (deoxyribonucleotides or ribonucleotides) of any length or analogs thereof. A polynucleotide may be single-stranded or double-stranded, and if single-stranded, it may be the coding strand or the non-coding (antisense) strand. A polynucleotide may contain modified nucleotides, such as methylated nucleotides and nucleotide analogs. The sequence of nucleotides may be interspersed with non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component. A nucleic acid may be a recombinant polynucleotide, or a polynucleotide from a genomic, cDNA, semi-synthetic or synthetic source that does not exist in nature or is linked to another polynucleotide in a non-natural arrangement.

[0536] As used herein, the term "isolated" refers to the removal of a substance from its original or native environment (e.g., the natural environment if it is naturally occurring). For example, a naturally occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide that has been separated from some or all of the coexisting substances in the natural system by human intervention is isolated. Such a polynucleotide may be part of a vector and / or such a polynucleotide or polypeptide may be part of a composition, and it is still isolated because such a vector or composition is not part of the environment in which it is found in nature.

[0537] In one embodiment, as used herein, the term "treat" (e.g., a complement-related disorder) means that when an antibody molecule is administered, the severity of the symptoms of an individual (e.g., a human) having and / or experiencing the symptoms of a disorder (e.g., a complement-related disorder) will be reduced and / or the individual will recover more quickly as compared to an individual who has not been administered the antibody molecule. In one embodiment, when treating a complement-related disorder, the levels of C5a and / or C5b in the treated individual may be lower as compared to a comparable untreated individual. For example, after administering an antibody molecule described herein for the effective treatment of an inflammatory disorder, diagnostic assays using immunofluorescence or electron microscopy will detect C5a and / or C5b in a biological sample of the individual. After treating an individual for a disorder, other assays (e.g., urine tests, blood tests, ultrasounds, X-rays, or cystoscopies) may also be used to monitor the treatment in the patient, or to detect the presence of symptoms of a disorder (e.g., a complement-related disorder), such as symptom reduction (or absence). Treatment can, for example, partially or fully alleviate, ameliorate, mitigate, inhibit, or reduce the severity of one or more clinical manifestations, features, and / or causes of the effects or symptoms of a disorder (e.g., a complement-related disorder), and / or reduce its incidence, and optionally, delay its onset. In one embodiment, treatment is used for individuals who do not exhibit certain signs of a disorder (e.g., a complement-related disorder), and / or who only exhibit early signs of a disorder (e.g., a complement-related disorder). In one embodiment, treatment is used for individuals who exhibit one or more established signs of a disorder (e.g., a complement-related disorder). In one embodiment, treatment is used for individuals diagnosed with a disorder (e.g., a complement-related disorder). In one embodiment, the disorder is a complement-related disorder as described herein.

[0538] As used herein, the term "prevent" a disorder (e.g., a complement-related disorder) means that if an individual (e.g., a human) receives an antibody molecule, then the individual is less likely to develop the disorder, e.g., a complement-related disorder. In one embodiment, the individual is at risk of developing a disorder (e.g., a complement-related disorder). In one embodiment, the disorder is a complement-related disorder as described herein.

[0539] Further details of various aspects of the compositions and methods herein are described below. Other definitions are set forth throughout the specification.

[0540] Complement component 5

[0541] Complement component 5 (also known as C5, C5D, C5a, C5b, CPAMD4, ECLZB, or complement C5) is a protein that in humans is encoded by the C5 gene.

[0542] C5 is the fifth component of the complement system and plays a role in inflammatory and cell-killing processes. C5 consists of α and β polypeptide chains linked by disulfide bridges. C5 is cleaved into C5a and C5b. The activated peptide C5a, which is an anaphylatoxin with spasmogenic and chemotactic activities, is derived from the α polypeptide via cleavage with C5-convertase. The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for the formation of the membrane attack complex that includes other complement components.

[0543] Exemplary complement pathways (including types, functions, and regulation) are described, for example, by Srijana Khanal, microbeonline.com / complement-system-pathways-functions-regulation / , November 5, 2017.

[0544] Exemplary amino acid and nucleotide sequences of human C5 are described, for example, in SEQ ID NO:53.

[0545] The amino acid sequence of human C5 is provided below.

[0546] Human C5 (SEQ ID NO:53)

[0547]

[0548] Other variants and alternative sequences of human C5 are provided as, for example, Genbank accession numbers NP_001304092.1 (isotype 2), NP_001304093.1 (isotype 3 precursor), and NP_001726.2 (isotype 1 preproprotein), as listed as of June 11, 2018. The corresponding nucleotide sequences encoding the human C5 sequences listed above are provided as Genbank accession numbers NM_001317163.1, NM_001317164.1, and NM_001735.2, as listed as of June 11, 2018.

[0549] Exemplary amino acid and nucleotide sequences of mouse C5 (also known as hemolytic complement, Hc, He, C5a, or Hfib2) are described, respectively, in, for example, Genbank accession numbers NP_034536.2 and NM_010406.2, as listed as of June 11, 2018.

[0550] The amino acid sequence of mouse C5 is provided below.

[0551] SEQ ID NO:93

[0552]

[0553] In one embodiment, when the anti-C5 antibody molecule binds or substantially binds to C5, it binds or substantially binds to one or more isotypes of C5, such as one or more isotypes of human C5 described herein. In one embodiment, the antibody molecule binds or substantially binds to C5 having the amino acid sequence of SEQ ID NO:53.

[0554] Antibody molecule

[0555] Antibody molecules that bind to C5 are disclosed herein, such as the anti-C5 antibody molecules described herein.

[0556] As used herein, the term "antibody molecule" refers to a protein that includes at least one immunoglobulin variable domain sequence, such as an immunoglobulin chain or a fragment thereof. The term "antibody molecule" includes, for example, full-length antibodies and antigen-binding fragments of antibodies.

[0557] For example, an antibody molecule may include a heavy (H) chain variable domain sequence (abbreviated herein as VH) and a light (L) chain variable domain sequence (abbreviated herein as VL). In another example, the antibody molecule includes two heavy (H) chain variable domain sequences and two light (L) chain variable domain sequences, thereby forming two antigen-binding sites, such as Fab, Fab', F(ab')2, Fc, Fd, Fd', Fv, single-chain antibodies (e.g., scFv or sc(Fv)2), single variable domain antibodies, bispecific antibodies (Dab) (bivalent and bispecific), and chimeric (e.g., humanized) antibodies, which may be produced from intact antibodies or modification of antibodies resynthesized using recombinant DNA techniques. These functional antibody fragments retain the ability to selectively bind to their corresponding antigen or receptor. Antibodies and antibody fragments can be from any antibody class, including (but not limited to) IgG, IgA, IgM, IgD, and IgE, and from any subclass of antibodies (e.g., IgG1, IgG2, IgG3, and IgG4). The antibody molecule can be monoclonal or polyclonal. In an embodiment, the antibody molecule is a full IgG antibody. The antibody molecule can also be a human, humanized, CDR-grafted, or in vitro-produced antibody. The antibody molecule can have a heavy chain constant region selected from, for example, IgG1, IgG2, IgG3, IgG4, or a chimera of two or more isotypes. The antibody molecule can also have a light chain selected from, for example, κ or λ. As used herein, the term "immunoglobulin" (Ig) can be used interchangeably with the term "antibody". In an embodiment, the antibody molecule is a multispecific antibody molecule (e.g., a bispecific antibody molecule).

[0558] Examples of antigen-binding fragments include: (i) Fab fragments, monovalent fragments consisting of the VL, VH, CL, and CH1 domains; (ii) F(ab')2 fragments, divalent fragments containing two Fab fragments linked by disulfide bridges in the hinge region; (iii) Fd fragments, consisting of the VH and CH1 domains; (iv) Fv fragments, consisting of the VL and VH domains of a single arm of an antibody; (v) diabody (dAb) fragments, consisting of the VH domain; (vi) camelid or camelized variable domains; (vii) single-chain Fv (scFv), see, e.g., Bird et al. (1988) Science 242:423-426; and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883; (viii) single-domain antibodies. These antibody fragments can be obtained using any suitable method, including several conventional techniques known to those skilled in the art, and can be screened for utility in the same manner as intact antibodies.

[0559] The term "antibody" includes intact molecules as well as functional fragments thereof. The constant region of an antibody can be altered (e.g., mutated) to modify the properties of the antibody (e.g., increase or decrease one or more of the following: Fc receptor binding, antibody glycosylation, the number of cysteine residues, effector cell function, or complement function).

[0560] In one embodiment, the antibody molecule is a single-chain antibody. Single-chain antibodies (scFV) can be engineered (see, e.g., Colcher, D. et al. (1999) Ann N Y Acad Sci 880:263-80; and Reiter, Y. (1996) Clin Cancer Res 2:245-52). Single-chain antibodies can be dimerized or multimerized to produce multivalent antibodies with specificity for different epitopes of the same target protein.

[0561] In one embodiment, the antibody molecule is a single-domain antibody. Single-domain antibodies can include antibodies in which the complementarity-determining regions are part of a single-domain polypeptide. Examples include (but are not limited to) heavy-chain antibodies, antibodies that are naturally devoid of light chains, single-domain antibodies derived from conventional four-chain antibodies, engineered antibodies, and single-domain scaffolds other than those derived from antibody frameworks. The single-domain antibody can be any of those in the art, or any future single-domain antibody. The single-domain antibody can be derived from any species, including (but not limited to) mouse, human, camel, llama, fish, shark, goat, rabbit, and cow. In one embodiment, the single-domain antibody is a naturally occurring single-domain antibody known as a heavy-chain antibody devoid of light chains. Such single-domain antibodies are disclosed, for example, in WO 94 / 04678. For clarity, the variable domain derived from such a heavy-chain antibody that is naturally devoid of light chains is referred to herein as a VHH or nanobody to distinguish it from the conventional VH of a four-chain immunoglobulin. Such VHH molecules can be derived from antibodies produced in Camelidae species (such as camel, llama, dromedary, alpaca, and vicuña). Other species besides Camelidae can produce heavy-chain antibodies that are naturally devoid of light chains; such VHHs are within the scope of the present invention.

[0562] The VH and VL regions can be further divided into hypervariable regions, called "complementarity-determining regions" (CDRs), which are interspersed with more conserved regions called "framework regions" (FR or FW). As used herein, the terms "complementarity-determining region" and "CDR" refer to the amino acid sequences within the variable region of an antibody that confer antigen specificity and binding affinity. Typically, there are three CDRs (HCDR1, HCDR2, HCDR3) in each heavy-chain variable region, and three CDRs (LCDR1, LCDR2, LCDR3) in each light-chain variable region. As used herein, the terms "framework", "FW", and "FR" are used interchangeably.

[0563] The extent of framework regions and CDRs has been precisely defined by a number of methods, see Kabat, E.A. et al., (1991) "Sequences of Proteins of Immunological Interest", 5th ed., U.S. Department of Health and Human Services, NIH Publication No. 91-3242 ("Kabat" numbering scheme); Chothia, C. et al. (1987) Journal of Molecular Biology 196:901-917 ("Chothia" numbering scheme); and the AbM definition used by the AbM antibody modeling software of Oxford Molecular. See generally, e.g., "Protein Sequence and Structure Analysis of Antibody Variable Domains", Antibody Engineering Lab Manual (Duebel, S. and Kontermann, R. eds., Springer-Verlag, Heidelberg). As used herein, a CDR defined according to the "Chothia" numbering scheme is sometimes also referred to as a "hypervariable loop". According to all definitions, each VH and VL generally includes three CDRs and four FRs, which are arranged in the following order from the amino-terminus to the carboxy-terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.

[0564] For example, according to Kabat, the CDR amino acid residues in the heavy chain variable domain (VH) are numbered 31 - 35 (HCDR1), 50 - 65 (HCDR2), and 95 - 102 (HCDR3); and the CDR amino acid residues in the light chain variable domain (VL) are numbered 24 - 34 (LCDR1), 50 - 56 (LCDR2), and 89 - 97 (LCDR3). According to Chothia, the CDR amino acid numbers in VH are 26 - 32 (HCDR1), 52 - 56 (HCDR2), and 95 - 102 (HCDR3); and the amino acid residues in VL are numbered 26 - 32 (LCDR1), 50 - 52 (LCDR2), and 91 - 96 (LCDR3). By combining the CDR definitions of Kabat and Chothia, the CDRs consist of amino acid residues 26 - 35 (HCDR1), 50 - 65 (HCDR2), and 95 - 102 (HCDR3) in human VH and amino acid residues 24 - 34 (LCDR1), 50 - 56 (LCDR2), and 89 - 97 (LCDR3) in human VL.

[0565] Generally, unless specifically specified otherwise, the anti - C5 antibody molecules described herein can include any combination of one or more Kabat CDRs and / or Chothia hypervariable loops, as described, for example, in Table 1.

[0566] As used herein, an "immunoglobulin variable domain sequence" refers to an amino acid sequence that can form the structure of an immunoglobulin variable domain. For example, the sequence can include all or a portion of the amino acid sequence of a naturally occurring variable domain. For example, the sequence can include or not include one, two, or more N - terminal or C - terminal amino acids, or can include other variations compatible with protein structure formation.

[0567] The term "antigen - binding region" refers to the portion of an antibody molecule that contains determinants that form an interface for binding to an antigen (such as C5, such as human C5) or its epitope. With respect to a protein (or protein mimetic), the antigen - binding region typically includes one or more loops (at least, for example, four amino acids or amino acid mimetics) that form an interface for binding to an antigen (such as C5, such as human C5). Generally, the antigen - binding region of an antibody molecule includes at least one or two CDRs and / or hypervariable loops, or more typically at least three, four, five, or six CDRs and / or hypervariable loops.

[0568] The terms "compete" or "cross-compete" are used interchangeably herein and refer to the ability of an antibody molecule to interfere with the binding of an anti-C5 antibody molecule (such as the anti-C5 antibody molecules provided herein) to a target (such as C5, such as human C5). The interference with binding can be direct or indirect (such as via allosteric modulation of the antibody molecule or the target). A competitive binding assay (such as FACS analysis, ELISA, or BIACORE assay) can be used to determine the extent to which an antibody molecule can interfere with the binding of another antibody molecule to a target and thus whether it can be termed a competitor. In one embodiment, the competitive binding assay is a quantitative competitive assay. In one embodiment, when in a competitive binding assay (such as the competitive assays described herein), the binding of a first antibody molecule to a target is reduced by 10% or more, such as 20% or more, 30% or more, 40% or more, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 98% or more, 99% or more, the first anti-C5 antibody molecule is said to compete with the second anti-C5 antibody molecule for binding to the target.

[0569] As used herein, the term "monoclonal antibody" or "monoclonal antibody composition" refers to a preparation of antibody molecules consisting of a single molecule. A monoclonal antibody composition exhibits a single binding specificity and affinity for a particular epitope. Monoclonal antibodies can be produced by hybridoma technology or by methods that do not use hybridoma technology (such as recombinant methods).

[0570] An "effective human" protein is a protein that does not elicit a neutralizing antibody response (such as a human anti-mouse antibody (HAMA) response). HAMA can be problematic in many situations, such as when an antibody molecule is administered repeatedly, such as in the treatment of chronic or recurrent disease conditions. The HAMA response can render repeated administration of the antibody potentially ineffective due to enhanced clearance of the antibody from the serum and potential allergic reactions (see, for example, Saleh et al., Cancer Immunol. Immunother., 32:180-190 (1990); LoBuglio et al., Hybridoma, 5:5117-5123 (1986)).

[0571] The antibody molecule can be a polyclonal or monoclonal antibody. In one embodiment, the antibody can be produced recombinantly, such as by any suitable phage display or combinatorial method.

[0572] A variety of phage display and combinatorial methods for generating antibodies are known in the art (e.g., Ladner et al. U.S. Patent No. 5,223,409; Kang et al. International Publication No. WO 92 / 18619; Dower et al. International Publication No. WO 91 / 17271; Winter et al. International Publication WO 92 / 20791; Markland et al. International Publication No. WO 92 / 15679; Breitling et al. International Publication WO 93 / 01288; McCafferty et al. International Publication No. WO 92 / 01047; Garrard et al. International Publication No. WO 92 / 09690; Ladner et al. International Publication No. WO 90 / 02809; Fuchs et al. (1991) Bio / Technology 9:1370-1372; Hay et al. (1992) Hum Antibod Hybridomas 3:81-85; Huse et al. (1989) Science 246:1275-1281; Griffiths et al. (1993) EMBO J 12:725-734; Hawkins et al. (1992) J Mol Biol 226:889-896; Clackson et al. (1991) Nature 352:624-628; Gram et al. (1992) PNAS 89:3576-3580; Garrad et al. (1991) Bio / Technology 9:1373-1377; Hoogenboom et al. (1991) Nuc Acid Res 19:4133-4137; and Barbas et al. (1991) PNAS 88:7978-7982, the contents of which are incorporated herein by reference).

[0573] In one embodiment, the antibody molecule is a fully human antibody (e.g., an antibody produced in a mouse that has been genetically engineered to produce an antibody derived from human immunoglobulin sequences), or a non-human antibody, such as a rodent (mouse or rat), goat, primate (e.g., monkey), camel antibody. In one embodiment, the non-human antibody is a rodent (e.g., a mouse or rat antibody). Methods for producing rodent antibodies are known in the art.

[0574] Human monoclonal antibodies can be produced using transgenic mice carrying human immunoglobulin genes instead of a murine system. Spleen cells from these transgenic mice immunized with the relevant antigen are used to generate hybridomas that secrete human mAbs having specific affinity for epitopes from human proteins (see, e.g., Wood et al. International Application WO91 / 00906; Kucherlapati et al. PCT Publication WO 91 / 10741; Lonberg et al. International Application WO 92 / 03918; Kay et al. International Application 92 / 03917; Lonberg, N. et al. 1994 Nature 368:856-859; Green, L.L. et al. 1994 Nature Genet. 7:13-21; Morrison, S.L. et al. 1994 Proc. Natl. Acad. Sci. USA 81:6851-6855; Bruggeman et al. 1993 Year Immunol. 7:33-40; Tuaillon et al. 1993 PNAS 90:3720-3724; Bruggeman et al. 1991 Eur J Immunol. 21:1323-1326).

[0575] The antibody can be an antibody in which the variable region or a portion thereof (e.g., CDR) is produced in a non-human organism (e.g., a rat or a mouse). Chimeric, CDR-grafted, and humanized antibodies are all within the scope of the present invention. Antibodies produced in a non-human organism (e.g., a rat or a mouse) and then modified in a human (e.g., in the variable framework or constant region) to reduce antigenicity are within the scope of the present invention.

[0576] Chimeric antibodies can be produced by any suitable recombinant DNA technique. Several techniques are known in the art (see Robinson et al., International Patent Publication No. WO1987 / 002671; Akira et al., European Patent Application Publication No. 184,187; Taniguchi, M., European Patent Application No. 171,496; Morrison et al., European Patent Application Publication No. 173,494; Neuberger et al., International Patent Application Publication No. WO 86 / 01533; Cabilly et al. U.S. Patent No. 4,816,567; Cabilly et al. European Patent Application Publication No. 125,023; Better et al. (1988) Science 240:1041-1043; Liu et al. (1987) PNAS 84:3439-3443; Liu et al., 1987, Journal of Immunology (J. Immunol.) 139:3521-3526; Sun et al. (1987) PNAS 84:214-218; Nishimura et al., 1987, Cancer Research (Canc. Res.) 47:999-1005; Wood et al. (1985) Nature 314:446-449; and Shaw et al., 1988, Journal of the National Cancer Institute (J. Natl Cancer Inst.) 80:1553-1559).

[0577] In a humanized or CDR-grafted antibody, at least one or two, but usually all three, recipient CDRs (CDRs of the heavy and / or light chain immunoglobulin chains) are replaced with donor CDRs. The antibody can be replaced with at least a portion of a non-human CDR or only some CDRs can be replaced with non-human CDRs. Only the number of CDRs required for the humanized antibody to bind to lipopolysaccharide need be replaced. In one embodiment, the donor is a rodent antibody, such as a rat or mouse antibody, and the recipient is a human framework or human consensus framework. Generally, the immunoglobulin providing the CDR is referred to as the "donor" and the immunoglobulin providing the framework is referred to as the "recipient". In one embodiment, the donor immunoglobulin is non-human (e.g., rodent). The recipient framework is typically a naturally occurring (e.g., human) framework or consensus framework, or a sequence that is about 85% or higher (e.g., 90%, 95%, 99% or higher) identical thereto.

[0578] As used herein, the term "consensus sequence" refers to a sequence formed by the amino acids (or nucleotides) that are most frequently present in a family of related sequences (see, e.g., Winnaker, From Genes to Clones (Verlagsgesellschaft, Weinheim, Germany, 1987)). In a protein family, each position in the consensus sequence is occupied by the amino acid that occurs most frequently at that position in the family. If two amino acids occur equally frequently, either may be included in the consensus sequence. A "consensus framework" refers to the framework regions in a consensus immunoglobulin sequence.

[0579] Antibodies can be humanized by any suitable method, and several such methods are known in the art (see, e.g., Morrison, S.L., 1985, Science 229:1202-1207, Oi et al., 1986, BioTechniques 4:214, and Queen et al. US 5,585,089, US 5,693,761, and US 5,693,762, the contents of which are hereby incorporated by reference in their entirety).

[0580] Humanized or CDR-grafted antibodies can be produced by CDR grafting or CDR replacement, in which one, two, or all of the CDRs in an immunoglobulin chain are replaced. See, e.g., U.S. Patent 5,225,539; Jones et al. 1986 Nature 321:552-525; Verhoeyan et al. 1988 Science 239:1534; Beidler et al. 1988 J. Immunol. 141:4053-4060; Winter U.S. Patent 5,225,539, the contents of which are hereby expressly incorporated by reference. Winter describes a CDR grafting method that can be used to prepare humanized antibodies (British Patent Application GB 2188638A, filed Mar. 26, 1987; Winter U.S. Patent 5,225,539), the contents of which are hereby expressly incorporated by reference.

[0581] Also provided are humanized antibodies in which specific amino acids have been substituted, deleted, or added. Guidelines for selecting amino acids from a donor are described, e.g., in US 5,585,089, e.g., lines 12-16 of US 5,585,089, the contents of which are hereby incorporated by reference. Other techniques for humanizing antibodies are described in Padlan et al. EP 519596A1 (published Dec. 23, 1992).

[0582] In one embodiment, the antibody molecule has a heavy chain constant region selected from heavy chain constant regions of, for example, IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgD, and IgE; specifically, from (e.g., human) heavy chain constant regions of, for example, IgG1, IgG2, IgG3, and IgG4. In another embodiment, the antibody molecule has a light chain constant region selected from (e.g., human) light chain constant regions of, for example, κ or λ. The constant regions are altered, e.g., by mutation to improve the properties of the antibody molecule (e.g., to increase or decrease one or more of: Fc receptor binding, antibody glycosylation, number of cysteine residues, effector cell function, and / or complement function). In one embodiment, the antibody molecule has effector function and can fix complement. In another embodiment, the antibody molecule does not recruit effector cells or fix complement. In one embodiment, the antibody molecule has a reduced or no ability to bind Fc receptors. For example, it can be an isotype or subtype, fragment, or other mutant that does not support binding to Fc receptors, e.g., it has a mutant or deleted Fc receptor binding region.

[0583] In one embodiment, the constant region of the antibody molecule is altered. Methods for altering antibody constant regions are known in the art. Antibody molecules with altered function (e.g., altered affinity for effector ligands such as FcR on cells or the C1 component of complement) can be generated by replacing at least one amino acid residue in the constant portion of the antibody with a different residue (see, e.g., EP 388,151A1, U.S. Patent No. 5,624,821, and U.S. Patent No. 5,648,260, the contents of which are incorporated herein by reference). Also encompassed are amino acid mutations in human IgG4 that stabilize the antibody structure, such as S228P (EU nomenclature, S241P in Kabat nomenclature). Similar types of changes that would reduce or eliminate these functions if applied to murine or other species immunoglobulins can be described.

[0584] In one embodiment, the only amino acids in the antibody molecule are standard amino acids. In some embodiments, the antibody molecule comprises naturally occurring amino acids; their analogs, derivatives, and homologs; amino acid analogs with variant side chains; and / or all stereoisomers of any of the foregoing. The antibody molecule can comprise D- or L-optical isomers of amino acids and peptidomimetics.

[0585] In one embodiment, the antibody molecule comprises a monoclonal antibody (e.g., a full-length antibody having an immunoglobulin Fc region). In one embodiment, the antibody molecule comprises a full-length antibody or a full-length immunoglobulin chain. In one embodiment, the antibody molecule comprises a full-length antibody or a full-length immunoglobulin chain antigen-binding or functional fragment.

[0586] In one embodiment, the antibody molecule is a monospecific antibody molecule, e.g., it binds a single epitope. For example, a monospecific antibody molecule can have multiple immunoglobulin variable region sequences, each of which binds the same epitope.

[0587] In one embodiment, the antibody molecule is a multispecific antibody molecule, e.g., it comprises multiple immunoglobulin variable region sequences, wherein a first immunoglobulin variable region sequence among the multiple immunoglobulin variable region sequences has binding specificity for a first epitope and a second immunoglobulin variable region sequence among the multiple immunoglobulin variable region sequences has binding specificity for a second epitope. In one embodiment, the first and second epitopes are on the same antigen, e.g., the same protein (or subunit of a multimeric protein). In one embodiment, the first and second epitopes overlap. In one embodiment, the first and second epitopes do not overlap. In one embodiment, the first and second epitopes are on different antigens, e.g., different proteins (or different subunits of a multimeric protein). In one embodiment, the multispecific antibody molecule comprises a third, fourth, or fifth immunoglobulin variable domain. In one embodiment, the multispecific antibody molecule is a bispecific antibody molecule, a trispecific antibody molecule, or a tetra-specific antibody molecule.

[0588] In one embodiment, the multispecific antibody molecule is a bispecific antibody molecule. A bispecific antibody is specific for no more than two antigens. A bispecific antibody molecule is typically characterized by a first immunoglobulin variable domain sequence having binding specificity for a first epitope and a second immunoglobulin variable domain sequence having binding specificity for a second epitope. In one embodiment, the first and second epitopes are on the same antigen, e.g., the same protein (or subunit of a multimeric protein). In one embodiment the first and second epitopes overlap. In one embodiment, the first and second epitopes do not overlap. In one embodiment, the first and second epitopes are on different antigens, e.g., different proteins (or different subunits of a multimeric protein). In one embodiment, the bispecific antibody molecule comprises a heavy chain variable region sequence and a light chain variable region sequence having binding specificity for a first epitope, and a heavy chain variable region sequence and a light chain variable region sequence having binding specificity for a second epitope. In one embodiment, the bispecific antibody molecule comprises a half antibody having binding specificity for a first epitope and a half antibody having binding specificity for a second epitope. In one embodiment, the bispecific antibody molecule comprises a half antibody or a fragment thereof having binding specificity for a first epitope and a half antibody or a fragment thereof having binding specificity for a second epitope. In one embodiment, the bispecific antibody molecule comprises a scFv or a fragment thereof having binding specificity for a first epitope and a scFv or a fragment thereof having binding specificity for a second epitope.

[0589] Protocols for generating bispecific or heterodimeric antibody molecules are known in the art; including (but not limited to) for example the "milling" method, as described in for example US5731168; electrostatic manipulation of Fc pairing, as described in for example WO 09 / 089004, WO 06 / 106905 and WO 2010 / 129304; chain exchange engineered domain (SEED) heterodimer formation, as described in for example WO 07 / 110205; Fab arm exchange, as described in for example WO 08 / 119353, WO 2011 / 131746 and WO2013 / 060867; diabody conjugates, for example generating bispecific structures by antibody cross-linking using hetero-bifunctional reagents having amine-reactive groups and thiol-reactive groups, as described in for example US 4433059; bispecific antibody determinants generated by recombinant half-antibodies (heavy chain-light chain pairs or Fabs) from different antibodies via disulfide reduction and oxidation cycles between two heavy chains, as described in for example US 4444878; trifunctional antibodies, for example three Fab' fragments cross-linked via thiol-reactive groups, as described in for example US5273743; biosynthetic binding proteins, for example scFv pairs cross-linked via C-terminal tails, preferably via disulfide bonds or amine-reactive chemical cross-linking, as described in for example US5534254; bispecific antibodies, for example Fab fragments having different binding specificities and dimerized via leucine zippers of replaced constant domains (for example, c-fos and c-jun), as described in for example US5582996; bispecific and oligospecific monovalent and oligovalent receptors, for example VH-CH1 regions of two antibodies (two Fab fragments) connected via a polypeptide spacer between the CH1 region of one antibody and the VH region of another antibody usually having an associated light chain, as described in for example US5591828; bispecific DNA-antibody conjugates, for example antibodies or Fab fragments cross-linked via double-stranded fragments of DNA, as described in for example US5635602; bispecific fusion proteins, for example expression constructs containing two scFvs and full constant regions with a hydrophilic helical peptide linker therebetween, as described in for example US5637481; multivalent and multispecific binding proteins, for example polypeptide dimers having a binding region with an Ig heavy chain variable region in the first domain and a binding region with an Ig light chain variable region in the second domain, commonly referred to as bispecific antibodies (also discloses higher order structures for generating bispecific, trispecific or tetraspecific molecules, as described in for example US5837242; minibody constructs with VL and VH chains connected, and the VL and VH chains further connected to the antibody hinge region and CH3 region via a peptide spacer, and the constructs can dimerize to form bispecific / multivalent molecules, as described in for example US5837821;VH and VL domains in any orientation, linked via a short peptide linker (e.g., 5 or 10 amino acids) or not linked via a linker at all, which may form dimers to form bispecific bifunctional antibodies; trimers and tetramers, as described, for example, in US5844094; a string of VH domains (or VL domains from family members) linked by peptide bond formation with a crosslinkable group at the C-terminus, which further associates with VL domains to form a series of Fv (or scFv), as described, for example, in US5864019; and single-chain binding polypeptides in which the VH and VL domains are linked via a peptide linker are combined into multivalent structures (using scFV or bispecific antibody-like forms) via non-covalent or chemical crosslinking to form, for example, homodivalent, heterodivalent, trivalent and tetravalent structures, as described, for example, in US5869620. The content of the above applications is incorporated herein by reference in its entirety.;

[0590] Other methods for preparing multispecific or bispecific antibody molecules can be found, for example, in US5910573, US5932448, US5959083, US5989830, US6005079, US6239259, US6294353, US6333396, US6476198, US6511663, US6670453, US6743896, US6809185, US6833441, US7129330, US7183076, US7521056, US7527787, US7534866, US7612181, US2002 / 004587, US2002 / 076406, US2002 / 103345, US2003 / 207346, US2003 / 211078, US2004 / 219643, US2004 / 220388, US2004 / 242847, US2005 / 003403, US2005 / 004352, US2005 / 069552, US2005 / 079170, US2005 / 100543, US2005 / 136049, US2005 / 136051, US2005 / 163782, US2005 / 266425, US2006 / 083747, US2006 / 120960, US2006 / 204493, US2006 / 263367, US2007 / 004909, US2007 / 087381, US2007 / 128150, US2007 / 141049, US2007 / 154901, US2007 / 274985, US2008 / 050370, US2008 / 069820, US2008 / 152645, US2008 / 171855, US2008 / 241884, US2008 / 254512, US2008 / 260738, US2009 / 130106, US2009 / 148905, US2009 / 155275, US2009 / 162359, US2009 / 162360, US2009 / 175851, US2009 / 175867, US2009 / 232811, US2009 / 234105, US2009 / 263392, US2009 / 274649, EP346087, WO00 / 06605, WO02 / 072635, WO04 / 081051, WO06 / 020258, WO2007 / 044887, WO2007 / 095338A2, WO2007 / 137760A2, WO2008 / 119353, WO2009 / 021754, WO2009 / 068630,WO91 / 03493, WO93 / 23537, WO94 / 09131, WO94 / 12625, WO95 / 09917, WO96 / 37621, WO99 / 64460. The contents of the above applications are incorporated herein by reference in their entirety.

[0591] The polypeptides of the antibody molecules described herein can be straight or branched chains, which can contain modified amino acids, and which can be interspersed with non-amino acids. The antibody molecules can also be modified; for example, by means such as disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as binding to a labeled component. The polypeptides can be isolated from natural sources, can be produced by eukaryotic or prokaryotic hosts by recombinant techniques, or can be the products of synthetic procedures.

[0592] The antibody molecules described herein can be used in unbound form alone, or can be conjugated to a substance, such as a toxin or a moiety (e.g., a therapeutic agent; a radiolabeled compound; a molecule of plant, fungal, or bacterial origin; or a biological protein (e.g., a protein toxin) or a particle (e.g., a recombinant viral particle, such as via a viral capsid protein). For example, an anti-C5 antibody can be conjugated to a radioisotope (such as an α-, β-, or γ-emitter, or a β- and γ-emitter).

[0593] The antibody molecules can be derivatized or linked to another functional molecule (e.g., another peptide or protein). As used herein, a "derivatized" antibody molecule is an antibody molecule that has been modified. Derivatization methods include (but are not limited to) adding a fluorescent moiety, a radiolabeled nucleotide, a toxin, an enzyme, or an affinity ligand, such as biotin. Thus, the antibody molecules are intended to include derivatized and otherwise modified forms of the antibodies described herein, including immunoadhesion molecules. For example, the antibody molecules can be functionally linked (by chemical conjugation, gene fusion, non-covalent binding, or otherwise) to one or more other molecular entities, such as another antibody (e.g., a bispecific or bifunctional antibody), a detectable reagent, a toxin, an agent, and / or a protein or peptide that can mediate the binding of the antibody or antibody moiety to another molecule (such as, the streptavidin core region or a polyhistidine tag).

[0594] Some types of derivatized antibody molecules are produced by crosslinking two or more antibodies (antibodies of the same type or different types, e.g., to produce bispecific antibodies). Suitable crosslinking agents include heterobifunctional crosslinking agents having two different reactive groups separated by a suitable spacer (e.g., m-maleimidobenzoyl-N-hydroxysuccinimide ester) or homobifunctional crosslinking agents (e.g., dibutyl succinate). Such crosslinking agents are available from Pierce Chemical Company, Rockford, Ill.

[0595] Suitable detectable reagents for derivatization (or labeling) of anti-dengue antibody molecules include fluorescent compounds, various enzymes, cofactors, luminescent substances, bioluminescent substances, fluorescent-emitting metal atoms (e.g., europium (Eu) and other lanthanide elements), and radioactive substances (described hereinafter). Exemplary fluorescent detectable reagents include fluorescein, fluorescein isothiocyanate, rhodamine, 5-dimethylamine-1-naphthalenesulfonyl chloride, phycoerythrin, etc. Antibodies can also be derivatized with detectable enzymes such as alkaline phosphatase, horseradish peroxidase, β-galactosidase, acetylcholinesterase, glucose oxidase, etc. When an antibody is derivatized with a detectable enzyme, it is detected by adding other reagents for the enzyme to produce a detectable reaction product. For example, when the detectable reagent horseradish peroxidase is present, the addition of hydrogen peroxide and diaminobenzidine produces a detectable colored reaction product. Antibody molecules can also be derivatized with cofactors (e.g., streptavidin / biotin and avidin / biotin). For example, an antibody can be derivatized with biotin and detected via indirect measurement of streptavidin or avidin binding. Examples of suitable fluorescent substances include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride, or phycoerythrin; examples of luminescent substances include luminol; and examples of bioluminescent substances include luciferase, luciferin, and aequorin.

[0596] Labeled antibody molecules can be used, e.g., in a diagnostic and / or experimental manner in a variety of situations, including (i) separating a predetermined antigen by standard techniques such as affinity chromatography or immunoprecipitation; (ii) detecting a predetermined antigen (e.g., in a cell lysate or cell supernatant) to assess protein abundance and expression patterns; (iii) monitoring protein content in tissues as part of a clinical test procedure, e.g., to determine the efficacy of an established treatment protocol.

[0597] The antibody molecules described herein can bind to another molecular entity, typically a label or a therapeutic (e.g., antimicrobial (e.g., antibacterial or bactericidal), immunomodulatory, immunostimulatory, cytotoxic or cytostatic) agent or moiety. Radioisotopes can be used in diagnostic or therapeutic applications. Radioisotopes that can be conjugated to the antibody molecule include (but are not limited to) α-, β- or γ-emitters, or β- and γ-emitters. Such radioisotopes include (but are not limited to) iodine ( 131 I or 125 I), yttrium ( 90 Y), lutetium ( 177 Lu), actinium ( 225 Ac), praseodymium, astatine ( 211 At), rhenium ( 186 Re), bismuth ( 212 Bi or 213 Bi), indium ( 111 In), technetium ( 99 mTc), phosphorus ( 32 P), rhodium ( 188 Rh), sulfur ( 35 S), carbon ( 14 C), tritium ( 3 H), chromium ( 51 Cr), chlorine ( 36 Cl), cobalt ( 57 Co or 58 Co), iron ( 59 Fe), selenium ( 75 Se) or gallium ( 67 Ga). Radioisotopes suitable for use as therapeutic agents include yttrium ( 90 Y), lutetium ( 177 Lu), actinium ( 225 Ac), praseodymium, astatine ( 211 At), rhenium ( 186 Re), bismuth ( 212 Bi or 213 Bi) and rhodium ( 188 Rh). Radioisotopes suitable for use as labels (e.g., for diagnostics) include iodine ( 131 I or 125 I), indium ( 111 In), technetium ( 99 mTc), phosphorus ( 32 P), carbon ( 14 C) and tritium ( 3 H), or one or more of the therapeutic isotopes listed above.

[0598] The present disclosure provides radiolabeled antibody molecules and methods for labeling antibody molecules. In one embodiment, a method for labeling an antibody molecule is disclosed. The method includes contacting the antibody molecule with a chelating agent, thereby producing a bound antibody. The bound antibody is radiolabeled with a radioisotope (e.g., 111 indium, 90 yttrium, and 177 lutetium), thereby producing a labeled antibody molecule.

[0599] In one embodiment, the antibody molecule is conjugated to a therapeutic agent. Therapeutically active radioisotopes are disclosed herein. Examples of other therapeutic agents include (but are not limited to) taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, maytansinoids (e.g., maytansinol (see U.S. Patent No. 5,208,020)), CC-1065 (see U.S. Patents Nos. 5,475,092, 5,585,499, 5,846,545) and analogs or homologs thereof.Therapeutic agents include, but are not limited to, antimetabolites (e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil, decarbazine), alkylating agents (e.g., mechlorethamine, thiotepa chlorambucil, CC-1065, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin), anthracyclinies (e.g., daunorubicin (formerly daunomycin) and doxorubicin), antibiotics (e.g., actinomycin D (formerly actinomycin), bleomycin, mithramycin, and anthramycin (AMC)), and antimitotic agents (e.g., vincristine, vinblastine, paclitaxel, and maytansinoids).

[0600] In one embodiment, an anti-C5 antibody molecule (e.g., a monospecific, bispecific, or multispecific antibody molecule) is covalently linked, e.g., fused, to another moiety (e.g., a protein, e.g., a fusion molecule (e.g., a fusion protein)).

[0601] As used herein, "fusion protein" and "fusion polypeptide" refer to a polypeptide having at least two moieties covalently linked together, where each of the moieties is a polypeptide. In one embodiment, each of the moieties is a polypeptide having different properties. The properties can be biological properties, such as in vitro or in vivo activity. The properties can also be simple chemical or physical properties, such as binding to a target molecule, catalyzing a reaction, etc. The two moieties can be directly linked by a single peptide bond or via a linker (e.g., a peptide linker), but are in reading frame with each other.

[0602] In one aspect, the present invention provides a method for providing a target binder that specifically binds to C5 (such as human C5). For example, the target binding molecule is an antibody molecule. The method includes: providing a target protein comprising at least a portion of a non-human protein, the portion being homologous to the corresponding portion of the human target protein (such as at least 70, 75, 80, 85, 87, 90, 92, 94, 95, 96, 97, 98% identical), but differing by at least one amino acid (such as at least one, two, three, four, five, six, seven, eight, or nine amino acids); obtaining a binder (such as an antibody molecule) that specifically binds to the target protein; and evaluating the efficacy of the binder in modulating the activity of the target protein. The method may further include administering the binder (such as an antibody molecule) or a derivative (such as a humanized antibody molecule) to an individual (such as a human individual).

[0603] In another aspect, the present disclosure provides a method for preparing the antibody molecules disclosed herein. The method includes: providi...

Claims

1. An isolated antibody or antigen-binding fragment thereof that binds to complement component 5, comprising: (a) A VH that comprises the HCDR1 amino acid sequence of SEQ ID NO:22; the HCDR2 amino acid sequence of SEQ ID NO:29; and the HCDR3 amino acid sequence of SEQ ID NO:35; and (b) A VL that comprises the LCDR1 amino acid sequence of SEQ ID NO:38, the LCDR2 amino acid sequence of SEQ ID NO:44, and the LCDR3 amino acid sequence of SEQ ID NO:49, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are according to the Chothia numbering.

2. An isolated antibody or antigen-binding fragment thereof that binds to complement component 5, comprising: (a) A VH that comprises the HCDR1 amino acid sequence of SEQ ID NO:55; the HCDR2 amino acid sequence of SEQ ID NO:60; and the HCDR3 amino acid sequence of SEQ ID NO:66; and (b) A VL that comprises the LCDR1 amino acid sequence of SEQ ID NO:71, the LCDR2 amino acid sequence of SEQ ID NO:77, and the LCDR3 amino acid sequence of SEQ ID NO:82, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are according to the Kabat numbering.

3. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which comprises a VH that comprises the amino acid sequence of SEQ ID NO:

4.

4. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which comprises a VL that comprises the amino acid sequence of SEQ ID NO:

11.

5. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which comprises a VH that comprises the amino acid sequence of SEQ ID NO:4 and a VL that comprises the amino acid sequence of SEQ ID NO:

11.

6. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which is an antigen-binding fragment.

7. The antibody or antigen-binding fragment thereof according to claim 6, wherein the antigen-binding fragment comprises Fab, F(ab')2, Fv, or scFv.

8. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which comprises a heavy chain constant region selected from IgG1, IgG2, IgG3, or IgG4 or a heavy chain constant region of a chimeric of two or more isotypes.

9. The antibody or antigen-binding fragment thereof according to claim 8, wherein the chimeric of two or more isotypes is an IgG2 / 4 chimeric.

10. The antibody or antigen-binding fragment thereof according to claim 8, wherein the heavy chain constant region comprises one or more amino acid modifications in the hinge, CH2, or CH3 region.

11. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which comprises a light chain constant region selected from κ or λ.

12. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which comprises a heavy chain constant region selected from the heavy chain constant regions of IgG1, IgG2, IgG3, IgG4 or a chimera of two or more isotypes, and a light chain constant region selected from the light chain constant regions of κ or λ.

13. The antibody or antigen-binding fragment thereof according to claim 12, wherein the chimera of two or more isotypes is a chimera of IgG2 and IgG4.

14. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which comprises an Fc region.

15. The antibody or antigen-binding fragment thereof according to claim 14, wherein the Fc region comprises one or both of the Met-428-Leu and Asn-434-Ser substitutions at the residues corresponding to methionine 428 and asparagine 434, respectively, according to EU numbering.

16. The antibody or antigen-binding fragment thereof according to claim 14, wherein the Fc region comprises one, two or three of the Met-252-Tyr, Ser-254-Thr and Thr-256-Glu substitutions at the residues corresponding to methionine 252, serine 254 and threonine 256, respectively, according to EU numbering.

17. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which comprises two VH and two VL.

18. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or antigen-binding fragment is a humanized antibody molecule.

19. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or antigen-binding fragment is a monoclonal antibody molecule.

20. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or antigen-binding fragment is a synthetic antibody molecule.

21. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or antigen-binding fragment is a monospecific antibody molecule.

22. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which is a multispecific antibody molecule.

23. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which is a bispecific antibody molecule.

24. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the complement component 5 is human complement component 5.

25. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which binds to human complement component 5 with a K D ' less than 0.1 μg / ml or 0.6 nM.

26. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which binds to human complement component 5 with a K between 0.03 and 0.08 μg / ml or between 0.2 nM and 0.53 nM D '.

27. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which binds to human complement component 5, as determined by ELISA, with an EC less than 2 μg / ml. 50 and binds to human complement component 5, as determined by ELISA.

28. The antibody or antigen-binding fragment thereof according to claim 27, which binds to human complement component 5 at an EC of less than 0.5 μg / ml, as determined by ELISA. 50 as determined by ELISA.

29. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which binds to human complement component 5 at an EC between 0.01 μg / ml and 2 μg / ml, as determined by ELISA. 50 ​ 30. The antibody or antigen-binding fragment thereof according to claim 29, which binds to human complement component 5 at an EC between 0.02 μg / ml and 0.2 μg / ml, as determined by ELISA. 50 ​ 31. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which binds to human complement component 5 at an EC between 0.03 μg / ml and 0.8 μg / ml, as determined by ELISA. 50 Binds to human complement component 5, as determined by ELISA.

32. The antibody or antigen-binding fragment thereof according to claim 31, which binds to human complement component 5 at an EC between 0.03 μg / ml and 0.16 μg / ml, as determined by ELISA. 50 ​ 33. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which inhibits hemolysis with an IC50 of less than 10 μg / ml, as determined by an in vitro hemolysis assay.

34. The antibody or antigen-binding fragment thereof according to claim 1 or 2, which inhibits hemolysis with an IC50 between 0.5 μg / ml and 6 μg / ml, as determined by an in vitro hemolysis assay.

35. The antibody or antigen-binding fragment thereof according to claim 34, which inhibits hemolysis with an IC50 between 2 μg / ml and 6 μg / ml, as determined by an in vitro hemolysis assay.

36. The antibody or antigen-binding fragment thereof according to claim 1 or 2 inhibits hemolysis with an IC50 between 0.5 μg / ml and 3.3 μg / ml, as determined by an in vitro hemolysis assay.

37. The antibody or antigen-binding fragment thereof according to claim 36 inhibits hemolysis with an IC50 between 2.3 μg / ml and 3.3 μg / ml, as determined by an in vitro hemolysis assay.

38. The antibody or antigen-binding fragment thereof according to claim 1 or 2 binds to human complement component 5 comprising the amino acid sequence of SEQ ID NO:

53.

39. The antibody or antigen-binding fragment thereof according to claim 1, wherein: (1) LCDR1, LCDR2, LCDR3, HCDR1, and HCDR2 belong to Chothia CDR canonical classes 2, 1, 1, 1, and 2, respectively; and (2) the antibody or antigen-binding fragment thereof comprises at least one of the complementarity-determining region-complementarity-determining region contacts selected from the group consisting of a) VH-30(Thr) and VH-28(Ile); b) VH-31(Asp) and VH-28(Ile) or VH-29(Phe); c) VH-32(Phe) and VH-94(Arg), VH-96(Phe), or VH-100(Trp); d) VH-94(Arg) and VH-101(Asp); e) VL-25(Ala) and VL-29(Ile) or VL-71(Phe); f) VL-55(Tyr) and VL-47(Leu) or VL-58(Val); g) VL-90(Gln) and VL-92(Leu), VL-93(Asn), VL-95(Pro), or VL-97(Ser); or h) VL-96(Val) and VL-98(Phe).

40. The antibody or antigen-binding fragment thereof according to claim 9, wherein the heavy chain constant region comprises one or more amino acid modifications in the hinge, CH2, or CH3 region.

41. A pharmaceutical composition comprising the isolated antibody or antigen-binding fragment thereof according to claim 1 or 2 and a pharmaceutically acceptable carrier, excipient, or stabilizer.

42. An isolated nucleic acid encoding the VH and VL of the antibody or antigen-binding fragment thereof according to claim 1 or 2.

43. An expression vector comprising the nucleic acid according to claim 42.

44. A host cell comprising the nucleic acid according to claim 42.

45. A method for preparing an antibody or antigen-binding fragment thereof, comprising culturing the host cell according to claim 44 under conditions suitable for gene expression, thereby expressing the antibody or antigen-binding fragment thereof according to claim 1 or 2.

46. A method for inhibiting complement component 5 in vitro or ex vivo, comprising contacting complement component 5 in vitro or ex vivo with the antibody or antigen-binding fragment thereof according to claim 1 or 2.

47. Use of the antibody or antigen-binding fragment thereof according to claim 1 or 2 in the preparation of a medicament or pharmaceutical composition for treating a disorder in an individual in need thereof, wherein the disorder is paroxysmal nocturnal hemoglobinuria (PNH).

48. Use according to claim 47, wherein the antibody or antigen-binding fragment thereof is administered to the individual at a dose between 0.1 mg / kg and 50 mg / kg.

49. A method for detecting complement component 5, comprising (i) contacting a sample with the antibody or antigen-binding fragment thereof according to claim 1 or 2 under conditions permitting interaction of the antibody or antigen-binding fragment thereof with complement component 5, and (ii) detecting the formation of a complex between the antibody or antigen-binding fragment thereof and the sample, the method being for non-diagnostic purposes.

50. The method according to claim 49, further comprising contacting a reference sample with the antibody or antigen-binding fragment thereof according to claim 1 or 2 under conditions permitting interaction of the antibody or antigen-binding fragment thereof with complement component 5, and (ii) detecting the formation of a complex between the antibody or antigen-binding fragment thereof and the sample.

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