Antibodies for use as a therapeutic agent against bacterial infections - Patents.com

Abstract

The present invention relates to antibodies that bind to Acinetobacter baumannii and their use in the diagnosis and prevention and treatment of bacterial infections caused by Acinetobacter baumannii. In particular, the present invention relates to monoclonal antibodies that specifically bind to the cell wall of Acinetobacter baumannii bacteria, for example on live bacteria.

Description

[Technical Field]

[0001] 1. Field of the Invention The present invention relates to antibodies that bind to Acinetobacter baumannii and their use in the diagnosis and prevention and treatment of bacterial infections caused by Acinetobacter baumannii. Mixed in 2. [Background technology]

[0002] 2.Background The genus Acinetobacter consists of 26 named species and 9 genomic species. Acinetobacter baumannii is a bacterial pathogen primarily associated with hospital-acquired infections. It is a Gram-negative bacillus.

[0003] Acinetobacter baumannii specifically targets moist tissues such as mucous membranes or exposed skin areas. If left untreated, this infection can lead to sepsis and death. The presence of Acinetobacter baumannii in hospital environments poses a significant risk, especially in intensive care units where patients suffer from chronic illnesses.

[0004] Carbapenems are beta-lactam antibiotics that are structurally distinct from other commonly used beta-lactam antibiotics, such as the penicillin and cephalosporin classes. Carbapenems have proven to be the drugs of choice for the treatment of extended-spectrum beta-lactamase (ESBL)-producing bacteria, including A. baumannii strains, which are associated with poor clinical outcomes in severe infections in hospital settings, such as pneumonia and bacteremia.

[0005] The World Health Organization has listed carbapenem-resistant Acinetobacter baumannii (CRAB) as one of the highest priority pathogens threatening human health. Indeed, CRAB is a significant cause of ventilator-associated pneumonia (VAP) in many countries in the developing and developed world, and has been found to cause over 30% of neonatal sepsis cases in several studies in the developing world.

[0006] Currently, the classification of Acinetobacter baumannii includes three European clones (ECI-III), eight worldwide clones (WW1-8—effectively becoming eight international clones, IC1-8), and two global clones (GC1 and GC2). ECI = WW1 = IC1, ECII = WW2 = IC2, and ECIII = WW3 = IC3 are all defined by multilocus sequence typing (MLST). Global clones 1 and 2, which correspond to IC1 and IC2, respectively, are also supported by whole-genome phylogenetic analysis (Pathog Dis. 2014 Aug;71(3):292-301. doi:10.1111 / 2049-632X.12125. Epub 2014 Jan 27, the contents of which are incorporated herein by reference).

[0007] Studies have shown that GC2 is the major global lineage associated with carbapenem resistance.

[0008] The present invention aims to provide a monoclonal antibody for the diagnosis and treatment of bacterial infections caused by Acinetobacter baumannii. Summary of the Invention [Means for solving the problem]

[0009] 3. Summary of the Invention The present invention provides monoclonal antibodies suitable for the diagnosis, prevention, and treatment of bacterial infections caused by Acinetobacter baumannii. In particular, the present invention provides monoclonal antibodies that specifically bind to the cell wall of Acinetobacter baumannii bacteria, e.g., on live bacteria. Advantageously, the present invention provides monoclonal antibodies that specifically bind to the bacterial wall of Acinetobacter baumannii bacteria and induce complement activation (e.g., as measured by a flow cytometry-based assay).

[0010] The present invention identifies novel antibody targets on the surface of Acinetobacter baumannii bacteria for the diagnosis, prevention, and treatment of bacterial infections caused by Acinetobacter baumannii. In particular, the present invention is the first to demonstrate that the Oxa-23 enzyme is present on the surface of live bacteria and can be targeted by diagnostic and therapeutic antibodies. Furthermore, the present invention is the first to demonstrate that the lipooligosaccharide (LOS)-type OC1 on the surface of live bacteria can be targeted by diagnostic and therapeutic antibodies. Finally, the present invention is the first to demonstrate that the KL49 carbohydrate capsular antigen on the surface of live bacteria can be targeted by diagnostic and therapeutic antibodies. Validation of these novel targets on the surface of Acinetobacter baumannii bacteria provides an important advance in the diagnosis, prevention, and treatment of bacterial infections caused by Acinetobacter baumannii. The present invention provides a particularly important advancement in the diagnosis, prevention, and treatment of bacterial infections caused by, but not limited to, carbapenem-resistant Acinetobacter baumannii (CRAB), for which existing carbapenem treatments are ineffective. As noted above, CRAB is particularly associated with the G2 lineage of Acinetobacter baumannii.

[0011] The present invention further provides novel monoclonal antibodies that bind to Oxa-23 on the surface of Acinetobacter baumannii bacteria. Such antibodies are particularly useful for diagnosing Acinetobacter baumannii. The present invention also provides novel antibodies that bind to Oxa-23 on the surface of Acinetobacter baumannii bacteria, induce complement activation, and thereby kill the bacteria. Such antibodies are particularly useful for preventing and treating bacterial infections caused by Acinetobacter baumannii.

[0012] The present invention further provides novel monoclonal antibodies that bind to the OC1 LOS on the surface of Acinetobacter baumannii bacteria. Such antibodies are particularly useful for diagnosing Acinetobacter baumannii. The present invention also provides novel antibodies that bind to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, induce complement activation, and thereby kill the bacteria. Such antibodies are particularly useful for preventing and treating bacterial infections caused by Acinetobacter baumannii.

[0013] The present invention further provides a novel monoclonal antibody that binds to KL49 on the surface of Acinetobacter baumannii bacteria. Such an antibody is particularly useful for diagnosing Acinetobacter baumannii. The present invention also provides a novel antibody that binds to KL49 on the surface of Acinetobacter baumannii bacteria, induces complement activation, and thereby kills the bacteria. Such an antibody is particularly useful for preventing and treating bacterial infections caused by Acinetobacter baumannii.

[0014] Antibody sequences are referred to herein by the internal reference number of the associated antibody as well as by the SEQ ID NO. Any disclosure herein that lists an antibody reference number is intended to include the disclosure with the corresponding nucleic acid or amino acid sequence number (SEQ ID NO) shown in Tables 1 and 2.

[0015] 3.1 Anti-Oxa-23 antibody Provided herein are antibodies that specifically bind to Oxa-23. For example, antibodies 1348, 1349, 1540, 1548, and 1550, exemplified herein, have been shown to specifically bind to Oxa-23 on outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria.

[0016] Provided are antibodies that specifically bind to Oxa-23 on the cell wall surface of Acinetobacter baumannii bacteria, e.g., on live bacteria. In one embodiment, the antibodies specifically bind to Oxa-23 on the surface of Acinetobacter baumannii bacteria, as measured by indirect whole-cell ELISA. Because there is a high correlation between outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria and live Acinetobacter baumannii bacteria, such antibodies have also been found to specifically bind to Oxa-23 on outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria.

[0017] In one embodiment, the antibody induces complement activation (eg, as measured by a flow cytometry-based assay).

[0018] In one embodiment, the antibody specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria and induces complement activation (e.g., as measured by a flow cytometry-based assay), and the HCDR3 is the HCDR3 of antibody 1348, 1349, 1540, 1548, or 1550.

[0019] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2 and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2 and LCDR3, wherein HCDR3 is the HCDR3 of antibody 1348, 1349, 1540, 1548 or 1550.

[0020] In one embodiment, the HCDR3 is the HCDR3 of antibody 1348.

[0021] In one embodiment, the HCDR3 is the HCDR3 of antibody 1349.

[0022] In one embodiment, the HCDR3 is the HCDR3 of antibody 1540.

[0023] In one embodiment, the HCDR3 is the HCDR3 of antibody 1548.

[0024] In one embodiment, the HCDR3 is the HCDR3 of antibody 1550.

[0025] In one embodiment, the invention provides an anti-Oxa-23 antibody, The antibody specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria and induces complement activation (as measured, for example, by a flow cytometry-based assay). the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2 and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2 and LCDR3; These six CDRs are those of antibodies 1348, 1349, 1540, 1548 or 1550.

[0026] In one embodiment, the invention provides an anti-Oxa-23 antibody, the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2 and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2 and LCDR3; These six CDRs are those of antibodies 1348, 1349, 1540, 1548 or 1550.

[0027] In one embodiment, the antibody has the six CDRs of antibody 1348.

[0028] In one embodiment, the antibody has the six CDRs of antibody 1349.

[0029] In one embodiment, the antibody has the six CDRs of antibody 1540.

[0030] In one embodiment, the antibody has the six CDRs of antibody 1548.

[0031] In one embodiment, the antibody has the six CDRs of antibody 1550.

[0032] In one embodiment, the antibody specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria and induces complement activation (e.g., as measured by a flow cytometry-based assay); The variable heavy (VH) domain and variable light (VL) domain sequences comprise the variable heavy (VH) domain and variable light (VL) domain sequences of antibody 1348, 1349, 1540, 1548 or 1550, respectively, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable heavy (VH) domain sequence, and optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable light (VL) domain sequence.

[0033] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and variable light (VL) domain sequence, respectively, comprise the variable heavy (VH) domain sequence and variable light (VL) domain sequence of antibody 1348, 1349, 1540, 1548, or 1550, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable heavy (VH) domain sequence, and optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable light (VL) domain sequence.

[0034] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1348, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1348, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0035] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1349, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1349, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0036] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1540, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1540, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0037] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1548, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1548, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0038] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1550, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1550, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0039] In one embodiment, the antibody specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria and induces complement activation (e.g., as measured by a flow cytometry-based assay); the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, the variable heavy (VH) domain sequence and the variable light (VL) domain sequence comprising sequences that have at least 90%, at least 95%, at least 98%, or at least 99% identity to the variable heavy (VH) domain sequence and variable light (VL) domain sequence of antibody 1348, 1349, 1540, 1548, or 1550, respectively; However, the antibodies have the CDRs of antibodies 1348, 1349, 1540, 1548, or 1550, respectively.

[0040] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence have at least 90%, at least 95%, at least 98%, or at least 99% identity to the variable heavy (VH) domain sequence and variable light (VL) domain sequence, respectively, of antibody 1348, 1349, 1540, 1548, or 1550; However, the antibodies have the CDRs of antibodies 1348, 1349, 1540, 1548, or 1550, respectively.

[0041] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1348, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1348, provided that the antibody has the CDRs of antibody 1348.

[0042] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1349, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1349, provided that the antibody has the CDRs of antibody 1349.

[0043] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the VH domain sequence of antibody 1540, and the variable light (VL) domain sequence comprises a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the VL domain sequence of antibody 1540, provided that the antibody has the CDRs of antibody 1540.

[0044] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1548, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1548, provided that the antibody has the CDRs of antibody 1548.

[0045] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the VH domain sequence of antibody 1550, and the variable light (VL) domain sequence comprises a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the VL domain sequence of antibody 1550, provided that the antibody has the CDRs of antibody 1550.

[0046] In one embodiment, the invention provides an antibody that specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria, wherein the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence comprise the variable heavy (VH) and variable light (VL) domain sequences of antibody 1348, 1349, 1540, 1548, or 1550, respectively.

[0047] In one embodiment, the antibody specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1348.

[0048] In one embodiment, the antibody specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1349.

[0049] In one embodiment, the antibody specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1540.

[0050] In one embodiment, the antibody specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1548.

[0051] In one embodiment, the antibody specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1550.

[0052] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence comprise the variable heavy (VH) and variable light (VL) domain sequences of antibody 1348, 1349, 1540, 1548, or 1550, respectively.

[0053] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1348.

[0054] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1349.

[0055] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1540.

[0056] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1548.

[0057] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1550.

[0058] In one example, the antibody is selected from the group consisting of antibodies 1348, 1349, 1540, 1548, or 1550.

[0059] In one embodiment, the antibody is antibody 1348.

[0060] In one embodiment, the antibody is antibody 1349.

[0061] In one embodiment, the antibody is antibody 1540.

[0062] In one embodiment, the antibody is antibody 1548.

[0063] In one embodiment, the antibody is antibody 1550.

[0064] Antibodies that bind to the same epitope on Oxa-23 as the antibodies described elsewhere herein are provided.

[0065] For example, antibodies are provided that bind to the same epitope as antibody 1348, 1349, 1540, 1548 or 1550, as defined by their VH and VL sequences.

[0066] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1348, as defined, for example, by its VH and VL sequences.

[0067] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1349, as defined, for example, by its VH and VL sequences.

[0068] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1540, as defined, for example, by its VH and VL sequences.

[0069] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1548, as defined, for example, by its VH and VL sequences.

[0070] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1550, as defined, for example, by its VH and VL sequences.

[0071] The antibody may contact Oxa-23 with a footprint that overlaps completely or partially with the footprint of an antibody disclosed elsewhere herein. As described elsewhere herein, competition between antibodies can be determined using, for example, SPR, to provide antibodies that compete with IgG antibodies for binding to Oxa-23 (compete for binding to their epitopes), as described elsewhere herein.

[0072] Antibodies of the invention may compete for binding to Oxa-23 with any of the anti-Oxa-23 antibodies described herein, such as antibodies 1348, 1349, 1540, 1548 and 1550, as defined by their respective VH and VL sequences.

[0073] The antibody of the present invention may compete with antibody 1348 for binding to Oxa-23.

[0074] The antibody of the present invention may compete with antibody 1349 for binding to Oxa-23.

[0075] The antibody of the present invention may compete with antibody 1540 for binding to Oxa-23.

[0076] The antibody of the present invention may compete with antibody 1548 for binding to Oxa-23.

[0077] The antibody of the present invention may compete with antibody 1550 for binding to Oxa-23.

[0078] Nucleic acid sequences provided by the invention may include sequences encoding the VH and / or VL domains of an anti-Oxa-23 antibody as defined anywhere herein.

[0079] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1348.

[0080] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1349.

[0081] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1540.

[0082] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1548.

[0083] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1550.

[0084] 3.2 Anti-OC1 LOS antibody Antibodies that specifically bind to OC1 lipooligosaccharide (LOS) are provided herein, such as antibodies 1042, 1043, 1403, 1405, 1407, 1408, and 1413, which have been shown to specifically bind to OC1 LOS on the surface of Acinetobacter baumannii bacteria.

[0085] Provided are antibodies that specifically bind to the OC1 LOS on the cell wall surface of Acinetobacter baumannii bacteria, e.g., on live bacteria. In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, as measured by indirect whole-cell ELISA. Because there is a high correlation between the outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria and live Acinetobacter baumannii bacteria, such antibodies have also been found to specifically bind to the OC1 LOS on the outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria.

[0086] In one embodiment, the antibody induces complement activation (eg, as measured by a flow cytometry-based assay).

[0087] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria and induces complement activation (e.g., as measured by a flow cytometry-based assay), and the HCDR3 is the HCDR3 of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413.

[0088] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3; The HCDR3 is the HCDR3 of antibody 1042, 1043, 1403, 1405, 1407, 1408 or 1413.

[0089] In one embodiment, the HCDR3 is the HCDR3 of antibody 1042.

[0090] In one embodiment, the HCDR3 is the HCDR3 of antibody 1043.

[0091] In one embodiment, the HCDR3 is the HCDR3 of antibody 1403.

[0092] In one embodiment, the HCDR3 is the HCDR3 of antibody 1405.

[0093] In one embodiment, the HCDR3 is the HCDR3 of antibody 1407.

[0094] In one embodiment, the HCDR3 is the HCDR3 of antibody 1408.

[0095] In one embodiment, the HCDR3 is the HCDR3 of antibody 1413.

[0096] In one embodiment, the invention provides an anti-OC1 LOS antibody, The antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria and induces complement activation (as measured, for example, by a flow cytometry-based assay). the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2 and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2 and LCDR3; These six CDRs are those of antibodies 1042, 1043, 1403, 1405, 1407, 1408 or 1413.

[0097] In one embodiment, the invention provides an anti-OC1 LOS antibody, the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2 and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2 and LCDR3; These six CDRs are those of antibodies 1042, 1043, 1403, 1405, 1407, 1408 or 1413.

[0098] In one embodiment, the antibody has the six CDRs of antibody 1042.

[0099] In one embodiment, the antibody has the six CDRs of antibody 1043.

[0100] In one embodiment, the antibody has the six CDRs of antibody 1403.

[0101] In one embodiment, the antibody has the six CDRs of antibody 1405.

[0102] In one embodiment, the antibody has the six CDRs of antibody 1407.

[0103] In one embodiment, the antibody has the six CDRs of antibody 1408.

[0104] In one embodiment, the antibody has the six CDRs of antibody 1413.

[0105] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria and induces complement activation (e.g., as measured by a flow cytometry-based assay); The variable heavy (VH) domain and variable light (VL) domain sequences comprise the variable heavy (VH) domain and variable light (VL) domain sequences of antibody 1042, 1043, 1403, 1405, 1407, 1408 or 1413, respectively, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable heavy (VH) domain sequence, and optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable light (VL) domain sequence.

[0106] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, respectively, of antibody 1042, 1043, 1403, 1405, 1407, 1408 or 1413, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable heavy (VH) domain sequence, and optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable light (VL) domain sequence.

[0107] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1042, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1042, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0108] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1043, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1043, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0109] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1403, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1403, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0110] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1405, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1405, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0111] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1407, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1407, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0112] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1408, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1408, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0113] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1413, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1413, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0114] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii and induces complement activation (e.g., as measured by a flow cytometry-based assay); the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence have at least 90%, at least 95%, at least 98%, or at least 99% identity to the variable heavy (VH) domain sequence and variable light (VL) domain sequence of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413, respectively; However, the antibodies have the six CDRs of antibodies 1042, 1043, 1403, 1405, 1407, 1408, or 1413, respectively.

[0115] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence have at least 90%, at least 95%, at least 98%, or at least 99% identity to the variable heavy (VH) domain sequence and the variable light (VL) domain sequence, respectively, of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413; However, the antibodies have the six CDRs of antibodies 1042, 1043, 1403, 1405, 1407, 1408, or 1413, respectively.

[0116] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1042, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1042, provided that the antibody has the six CDRs of antibody 1042.

[0117] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1043, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1043, provided that the antibody has the six CDRs of antibody 1043.

[0118] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1403, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1403, with the proviso that the antibody has the six CDRs of antibody 1403.

[0119] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1405, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1405, with the proviso that the antibody has the six CDRs of antibody 1405.

[0120] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1407, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1407, provided that the antibody has the six CDRs of antibody 1407.

[0121] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1408, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1408, provided that the antibody has the six CDRs of antibody 1408.

[0122] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1413, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1413, with the proviso that the antibody has the six CDRs of antibody 1413.

[0123] In one embodiment, the invention provides an antibody that specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, The antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence comprise the variable heavy (VH) and variable light (VL) domain sequences of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413, respectively.

[0124] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1042.

[0125] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1043.

[0126] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1403.

[0127] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1405.

[0128] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1407.

[0129] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1408.

[0130] In one embodiment, the antibody specifically binds to the OC1 LOS on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1413.

[0131] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence comprise the variable heavy (VH) and variable light (VL) domain sequences of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413, respectively.

[0132] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1042.

[0133] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1043.

[0134] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1403.

[0135] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1405.

[0136] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1407.

[0137] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1408.

[0138] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1413.

[0139] In one embodiment, the antibody is selected from the group consisting of antibodies 1042, 1043, 1403, 1405, 1407, 1408, and 1413.

[0140] In one embodiment, the antibody is antibody 1042.

[0141] In one embodiment, the antibody is antibody 1043.

[0142] In one embodiment, the antibody is antibody 1403.

[0143] In one embodiment, the antibody is antibody 1405.

[0144] In one embodiment, the antibody is antibody 1407.

[0145] In one embodiment, the antibody is antibody 1408.

[0146] In one embodiment, the antibody is antibody 1413.

[0147] Antibodies are provided that bind to the same epitope on OC1 LOS as the antibodies described elsewhere herein.

[0148] For example, antibodies that bind to the same epitope as antibody 1042, 1043, 1403, 1405, 1407, 1408 or 1413, as defined by their VH and VL sequences, are provided.

[0149] In one embodiment, an antibody that binds to the same epitope as antibody 1042 is provided.

[0150] In one embodiment, an antibody that binds to the same epitope as antibody 1043 is provided.

[0151] In one embodiment, an antibody that binds to the same epitope as antibody 1403 is provided.

[0152] In one embodiment, an antibody that binds to the same epitope as antibody 1405 is provided.

[0153] In one embodiment, an antibody that binds to the same epitope as antibody 1407 is provided.

[0154] In one embodiment, an antibody that binds to the same epitope as antibody 1408 is provided.

[0155] In one embodiment, an antibody that binds to the same epitope as antibody 1413 is provided.

[0156] The antibodies may contact OC1 LOS with a footprint that overlaps completely or partially with the footprint of an antibody disclosed elsewhere herein. As described elsewhere herein, competition between antibodies can be determined using, for example, SPR, to provide antibodies that compete with an IgG antibody for binding to OC1 LOS (compete for binding to their epitopes), as described elsewhere herein.

[0157] The antibodies of the invention can compete for binding to OC1 LOS on the surface of Acinetobacter baumannii bacteria with any of the anti-OC1 LOS antibodies described herein, such as antibodies 1042, 1043, 1403, 1405, 1407, 1408, and 1413, as defined by their VH and VL sequences.

[0158] The antibody of the present invention may compete with antibody 1042 for binding to OC1 LOS.

[0159] The antibody of the present invention may compete with antibody 1043 for binding to OC1 LOS.

[0160] The antibody of the present invention may compete with antibody 1403 for binding to OC1 LOS.

[0161] The antibody of the present invention may compete with antibody 1405 for binding to OC1 LOS.

[0162] The antibody of the present invention may compete with antibody 1407 for binding to OC1 LOS.

[0163] The antibody of the present invention may compete with antibody 1408 for binding to OC1 LOS.

[0164] The antibody of the present invention may compete with antibody 1413 for binding to OC1 LOS.

[0165] Nucleic acid sequences provided by the invention may include sequences encoding the VH and / or VL domains of an anti-OC1 LOS antibody as defined anywhere herein.

[0166] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1042.

[0167] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1043.

[0168] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1403.

[0169] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1405.

[0170] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1407.

[0171] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1408.

[0172] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1413.

[0173] 3.3 Anti-KL49 antibody Antibodies that specifically bind to KL49 are provided herein. For example, antibodies 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, and 1416 exemplified herein have been shown to specifically bind to KL49 on the surface of Acinetobacter baumannii bacteria.

[0174] Provided are antibodies that specifically bind to KL49 on the cell wall surface of Acinetobacter baumannii bacteria, e.g., on live bacteria. In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, as measured by indirect whole-cell ELISA. Because there is a high correlation between outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria and live Acinetobacter baumannii bacteria, such antibodies have also been found to specifically bind to KL49 on outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria.

[0175] In one embodiment, the antibody induces complement activation (eg, as measured by a flow cytometry-based assay).

[0176] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii and induces complement activation (e.g., as measured by a flow cytometry-based assay), and the HCDR3 is the HCDR3 of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416.

[0177] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3; The HCDR3 is the HCDR3 of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415 or 1416.

[0178] In one embodiment, the HCDR3 is the HCDR3 of antibody 1345.

[0179] In one embodiment, the HCDR3 is the HCDR3 of antibody 1347.

[0180] In one embodiment, the HCDR3 is the HCDR3 of antibody 1350.

[0181] In one embodiment, the HCDR3 is the HCDR3 of antibody 1351.

[0182] In one embodiment, the HCDR3 is the HCDR3 of antibody 1363.

[0183] In one embodiment, the HCDR3 is the HCDR3 of antibody 1364.

[0184] In one embodiment, the HCDR3 is the HCDR3 of antibody 1397.

[0185] In one embodiment, the HCDR3 is the HCDR3 of antibody 1398.

[0186] In one embodiment, the HCDR3 is the HCDR3 of antibody 1400.

[0187] In one embodiment, the HCDR3 is the HCDR3 of antibody 1401.

[0188] In one embodiment, the HCDR3 is the HCDR3 of antibody 1402.

[0189] In one embodiment, the HCDR3 is the HCDR3 of antibody 1404.

[0190] In one embodiment, the HCDR3 is the HCDR3 of antibody 1409.

[0191] In one embodiment, the HCDR3 is the HCDR3 of antibody 1410.

[0192] In one embodiment, the HCDR3 is the HCDR3 of antibody 1412.

[0193] In one embodiment, the HCDR3 is the HCDR3 of antibody 1414.

[0194] In one embodiment, the HCDR3 is the HCDR3 of antibody 1415.

[0195] In one embodiment, the HCDR3 is the HCDR3 of antibody 1416.

[0196] In one embodiment, the invention provides an anti-KL49 antibody, The antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, induces complement activation (e.g., as measured by a flow cytometry-based assay), and the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2 and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2 and LCDR3; These six CDRs are those of antibodies 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415 or 1416.

[0197] In one embodiment, the invention provides an anti-KL49 antibody, the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2 and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2 and LCDR3; These six CDRs are those of antibodies 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415 or 1416.

[0198] In one embodiment, the antibody has the six CDRs of antibody 1345.

[0199] In one embodiment, the antibody has the six CDRs of antibody 1347.

[0200] In one embodiment, the antibody has the six CDRs of antibody 1350.

[0201] In one embodiment, the antibody has the six CDRs of antibody 1351.

[0202] In one embodiment, the antibody has the six CDRs of antibody 1363.

[0203] In one embodiment, the antibody has the six CDRs of antibody 1364.

[0204] In one embodiment, the antibody has the six CDRs of antibody 1397.

[0205] In one embodiment, the antibody has the six CDRs of antibody 1398.

[0206] In one embodiment, the antibody has the six CDRs of antibody 1400.

[0207] In one embodiment, the antibody has the six CDRs of antibody 1401.

[0208] In one embodiment, the antibody has the six CDRs of antibody 1402.

[0209] In one embodiment, the antibody has the six CDRs of antibody 1404.

[0210] In one embodiment, the antibody has the six CDRs of antibody 1409.

[0211] In one embodiment, the antibody has the six CDRs of antibody 1410.

[0212] In one embodiment, the antibody has the six CDRs of antibody 1412.

[0213] In one embodiment, the antibody has the six CDRs of antibody 1414.

[0214] In one embodiment, the antibody has the six CDRs of antibody 1415.

[0215] In one embodiment, the antibody has the six CDRs of antibody 1416.

[0216] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria and induces complement activation (e.g., as measured by a flow cytometry-based assay); The variable heavy (VH) domain sequence and variable light (VL) domain sequence comprise the variable heavy (VH) domain sequence and variable light (VL) domain sequence of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415 or 1416, respectively, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable heavy (VH) domain sequence, and optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable light (VL) domain sequence.

[0217] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, respectively, of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable heavy (VH) domain sequence, and optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable light (VL) domain sequence.

[0218] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1345, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1345, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0219] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1347, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1347, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0220] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1350, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1350, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0221] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1351, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1351, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0222] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1363, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1363, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0223] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1364, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1364, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0224] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1397, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1397, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0225] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1398, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1398, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0226] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1400, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1400, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0227] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1401, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1401, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0228] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1402, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1402, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0229] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1404, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1404, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0230] In one embodiment, the antibody comprises the variable heavy (VH) domain sequence of antibody 1409, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1409, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0231] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1410, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1410, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0232] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1412, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1412, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0233] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1414, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1414, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0234] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1415, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1415, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0235] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence of antibody 1416, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs), and a variable light (VL) domain sequence of antibody 1416, optionally with 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs).

[0236] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria and induces complement activation (e.g., as measured by a flow cytometry-based assay); the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence have at least 90%, at least 95%, at least 98%, or at least 99% identity to the variable heavy (VH) domain sequence and the variable light (VL) domain sequence, respectively, of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416; provided that the antibodies have the six CDRs of antibodies 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416, respectively.

[0237] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence, respectively, have at least 90%, at least 95%, at least 98%, or at least 99% identity to the variable heavy (VH) domain sequence and the variable light (VL) domain sequence of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416; provided that the antibodies have the six CDRs of antibodies 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416, respectively.

[0238] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1345, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1345, provided that the antibody has the six CDRs of antibody 1345.

[0239] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1347, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1347, provided that the antibody has the six CDRs of antibody 1347.

[0240] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1350, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1350, provided that the antibody has the six CDRs of antibody 1350.

[0241] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1351, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1351, provided that the antibody has the six CDRs of antibody 1351.

[0242] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1363, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1363, provided that the antibody has the six CDRs of antibody 1363.

[0243] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1364, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1364, provided that the antibody has the six CDRs of antibody 1364.

[0244] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1397, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1397, provided that the antibody has the six CDRs of antibody 1397.

[0245] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1398, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1398, provided that the antibody has the six CDRs of antibody 1398.

[0246] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1400, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1400, provided that the antibody has the six CDRs of antibody 1400.

[0247] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1401, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1401, with the proviso that the antibody has the six CDRs of antibody 1401.

[0248] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the VH domain sequence of antibody 1402, and the variable light (VL) domain sequence comprises a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the VL domain sequence of antibody 1402, with the proviso that the antibody has the six CDRs of antibody 1402.

[0249] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the VH domain sequence of antibody 1404, and the variable light (VL) domain sequence comprises a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to the VL domain sequence of antibody 1404, with the proviso that the antibody has the six CDRs of antibody 1404.

[0250] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1409, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1409, provided that the antibody has the six CDRs of antibody 1409.

[0251] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1410, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1410, provided that the antibody has the six CDRs of antibody 1410.

[0252] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1412, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1412, with the proviso that the antibody has the six CDRs of antibody 1412.

[0253] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1414, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1414, provided that the antibody has the six CDRs of antibody 1414.

[0254] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1415, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1415, with the proviso that the antibody has the six CDRs of antibody 1415.

[0255] In one embodiment, the variable heavy (VH) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1416, and the variable light (VL) domain sequence comprises a sequence that is at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1416, with the proviso that the antibody has the six CDRs of antibody 1416.

[0256] In one embodiment, the invention provides an antibody that specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, The antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and variable light (VL) domain sequence comprise the variable heavy (VH) domain sequence and variable light (VL) domain sequence of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416, respectively.

[0257] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1345.

[0258] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1347.

[0259] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1350.

[0260] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1351.

[0261] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1363.

[0262] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1364.

[0263] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1397.

[0264] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1398.

[0265] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1400.

[0266] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1401.

[0267] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1402.

[0268] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1404.

[0269] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1409.

[0270] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1410.

[0271] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1412.

[0272] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1414.

[0273] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1415.

[0274] In one embodiment, the antibody specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria, and the antibody comprises the VH and VL domain sequences of antibody 1416.

[0275] In one embodiment, the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and variable light (VL) domain sequence comprise the variable heavy (VH) domain sequence and variable light (VL) domain sequence, respectively, of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416.

[0276] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1345.

[0277] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1347.

[0278] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1350.

[0279] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1351.

[0280] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1363.

[0281] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1364.

[0282] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1397.

[0283] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1398.

[0284] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1400.

[0285] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1401.

[0286] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1402.

[0287] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1404.

[0288] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1409.

[0289] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1410.

[0290] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1412.

[0291] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1414.

[0292] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1415.

[0293] In one embodiment, the antibody comprises the VH and VL domain sequences of antibody 1416.

[0294] In one embodiment, the antibody is selected from the group consisting of antibodies 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415 and 1416.

[0295] In one embodiment, the antibody is antibody 1345.

[0296] In one embodiment, the antibody is antibody 1347.

[0297] In one embodiment, the antibody is antibody 1350.

[0298] In one embodiment, the antibody is antibody 1351.

[0299] In one embodiment, the antibody is antibody 1363.

[0300] In one embodiment, the antibody is antibody 1364.

[0301] In one embodiment, the antibody is antibody 1397.

[0302] In one embodiment, the antibody is antibody 1398.

[0303] In one embodiment, the antibody is antibody 1400.

[0304] In one embodiment, the antibody is antibody 1401.

[0305] In one embodiment, the antibody is antibody 1402.

[0306] In one embodiment, the antibody is antibody 1404.

[0307] In one embodiment, the antibody is antibody 1409.

[0308] In one embodiment, the antibody is antibody 1410.

[0309] In one embodiment, the antibody is antibody 1412.

[0310] In one embodiment, the antibody is antibody 1414.

[0311] In one embodiment, the antibody is antibody 1415.

[0312] In one embodiment, the antibody is antibody 1416.

[0313] Antibodies are provided that bind to the same epitope on KL49 as the antibodies described elsewhere herein.

[0314] For example, antibodies are provided that bind to the same epitope as antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415 or 1416 as defined by their VH and VL sequences.

[0315] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1345, as defined, for example, by its VH and VL sequences.

[0316] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1347, as defined, for example, by its VH and VL sequences.

[0317] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1350, as defined, for example, by its VH and VL sequences.

[0318] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1351, as defined, for example, by its VH and VL sequences.

[0319] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1363, as defined, for example, by its VH and VL sequences.

[0320] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1364, as defined, for example, by its VH and VL sequences.

[0321] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1397, as defined, for example, by its VH and VL sequences.

[0322] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1398, as defined, for example, by its VH and VL sequences.

[0323] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1400, as defined, for example, by its VH and VL sequences.

[0324] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1401, as defined, for example, by its VH and VL sequences.

[0325] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1402, as defined, for example, by its VH and VL sequences.

[0326] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1404, as defined, for example, by its VH and VL sequences.

[0327] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1409, as defined, for example, by its VH and VL sequences.

[0328] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1410, as defined, for example, by its VH and VL sequences.

[0329] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1412, as defined, for example, by its VH and VL sequences.

[0330] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1414, as defined, for example, by its VH and VL sequences.

[0331] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1415, as defined, for example, by its VH and VL sequences.

[0332] In one embodiment, an antibody is provided that binds to the same epitope as antibody 1416, as defined, for example, by its VH and VL sequences.

[0333] The antibody may contact KL49 with a footprint that overlaps completely or partially with the footprint of an antibody disclosed elsewhere herein. As described elsewhere herein, competition between antibodies can be determined using, for example, SPR, to provide antibodies that compete with an IgG antibody for binding to KL49 (compete for binding to their epitopes), as described elsewhere herein.

[0334] Antibodies of the invention may compete for binding to KL49 with any of the anti-KL49 antibodies described herein, such as, for example, antibodies 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415 and 1416, as defined by their respective VH and VL sequences.

[0335] The antibody of the present invention may compete with antibody 1345 for binding to KL49.

[0336] The antibody of the present invention may compete with antibody 1347 for binding to KL49.

[0337] The antibody of the present invention may compete with antibody 1350 for binding to KL49.

[0338] The antibody of the present invention may compete with antibody 1351 for binding to KL49.

[0339] The antibody of the present invention may compete with antibody 1363 for binding to KL49.

[0340] The antibody of the present invention may compete with antibody 1364 for binding to KL49.

[0341] The antibody of the present invention may compete with antibody 1397 for binding to KL49.

[0342] The antibody of the present invention may compete with antibody 1398 for binding to KL49.

[0343] The antibody of the present invention may compete with antibody 1400 for binding to KL49.

[0344] The antibody of the present invention may compete with antibody 1401 for binding to KL49.

[0345] The antibody of the present invention may compete with antibody 1402 for binding to KL49.

[0346] The antibody of the present invention may compete with antibody 1404 for binding to KL49.

[0347] The antibody of the present invention may compete with antibody 1409 for binding to KL49.

[0348] The antibody of the present invention may compete with antibody 1410 for binding to KL49.

[0349] The antibody of the present invention may compete with antibody 1412 for binding to KL49.

[0350] The antibody of the present invention may compete with antibody 1414 for binding to KL49.

[0351] The antibody of the present invention may compete with antibody 1415 for binding to KL49.

[0352] The antibody of the present invention may compete with antibody 1416 for binding to KL49.

[0353] Nucleic acid sequences provided by the present invention may include sequences encoding the VH and / or VL domains of an anti-KL49 antibody as defined anywhere herein.

[0354] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1345.

[0355] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1347.

[0356] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1350.

[0357] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1351.

[0358] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1363.

[0359] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1364.

[0360] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1397.

[0361] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1398.

[0362] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1400.

[0363] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1401.

[0364] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1402.

[0365] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1404.

[0366] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1409.

[0367] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1410.

[0368] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1412.

[0369] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1414.

[0370] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1415.

[0371] The nucleic acid may comprise a sequence encoding the VH and / or VL domain of antibody 1416.

[0372] 3.4 Antibodies in general In one embodiment, an antibody as defined anywhere herein exhibits complement dependent cytotoxicity (CDC) activity.

[0373] An antibody defined anywhere herein may be a human IgG1 or a human IgG4. In one embodiment, the antibody is a human IgG1. In one embodiment, the antibody is a human IgG1 comprising the constant region sequence of SEQ ID NO: 418. In one embodiment, the antibody is a human IgG4. In one embodiment, the antibody is a human IgG4 comprising the constant region sequence of SEQ ID NO: 436.

[0374] An antibody defined anywhere herein may be a human IgA1 (eg, comprising the constant region sequence of SEQ ID NO: 484) or a human IgA2 (eg, comprising the constant region sequence of SEQ ID NO: 485).

[0375] An antibody defined anywhere herein may comprise a kappa (κ) light chain constant region, preferably the constant domain sequence of SEQ ID NO: 448. The invention provides a vector comprising a nucleic acid defined anywhere herein, optionally the vector is a CHO vector.

[0376] The present invention provides a host cell comprising a nucleic acid as defined anywhere herein, or a vector as defined anywhere herein.

[0377] The present invention provides a pharmaceutical composition comprising an antibody as defined anywhere herein and a pharmaceutically acceptable excipient.

[0378] The invention provides a pharmaceutical composition comprising an isolated nucleic acid encoding an antibody as defined anywhere herein, or an isolated nucleic acid as defined anywhere herein, and a pharmaceutically acceptable excipient.

[0379] In one embodiment, the pharmaceutical composition is formulated for administration by injection.

[0380] In one embodiment, the pharmaceutical composition is formulated for intravenous, intramuscular, or subcutaneous administration.

[0381] In one embodiment, the pharmaceutical composition further comprises at least one additional therapeutic agent.

[0382] In one embodiment, the additional therapeutic agent is at least one, preferably one or two, additional antibodies.

[0383] In one embodiment, the additional therapeutic agent is a carbapenem.

[0384] In one embodiment, the additional therapeutic agent is colistin.

[0385] In one embodiment, the pharmaceutical composition comprises a first antibody that specifically binds to Oxa-23 and a second antibody that specifically binds to OC1 LOS.

[0386] In one embodiment, the pharmaceutical composition comprises a first antibody that specifically binds to Oxa-23 and a second antibody that specifically binds to KL49.

[0387] In one embodiment, the pharmaceutical composition comprises a first antibody that specifically binds to OC1 LOS and a second antibody that specifically binds to KL49.

[0388] In one embodiment, the pharmaceutical composition comprises a first antibody that specifically binds to Oxa-23, a second antibody that specifically binds to OC1 LOS, and a third antibody that specifically binds to KL49.

[0389] The present invention provides a diagnostic kit comprising at least one antibody defined anywhere herein. In one embodiment, the diagnostic kit comprises a first antibody that specifically binds to Oxa-23 and a second antibody that specifically binds to OC1 LOS. In one embodiment, the diagnostic kit comprises a first antibody that specifically binds to Oxa-23 and a second antibody that specifically binds to KL49. In one embodiment, the diagnostic kit comprises a first antibody that specifically binds to OC1 LOS and a second antibody that specifically binds to KL49. In one embodiment, the diagnostic kit comprises a first antibody that specifically binds to Oxa-23, a second antibody that specifically binds to OC1 LOS, and a third antibody that specifically binds to KL49.

[0390] The present invention provides a kit comprising a pharmaceutical composition as defined anywhere herein. In one embodiment, the kit further comprises at least one additional therapeutic agent. In one embodiment, the additional therapeutic agent is an additional pharmaceutical composition comprising at least one, preferably one or two, additional antibodies. In one embodiment, the kit further comprises a carbapenem. In one embodiment, the kit further comprises colistin.

[0391] In one embodiment, the at least one additional antibody is selected from an antibody that specifically binds to Oxa-23, an antibody that specifically binds to OC1 LOS, and an antibody that specifically binds to KL49.

[0392] In one embodiment, the kit comprises a first antibody that specifically binds to Oxa-23 and a second antibody that specifically binds to OC1 LOS.

[0393] In one embodiment, the kit comprises a first antibody that specifically binds to Oxa-23 and a second antibody that specifically binds to KL49.

[0394] In one embodiment, the kit comprises a first antibody that specifically binds to OC1 LOS and a second antibody that specifically binds to KL49.

[0395] In one embodiment, the kit comprises a first antibody that specifically binds to Oxa-23, a second antibody that specifically binds to OC1 LOS, and a third antibody that specifically binds to KL49.

[0396] In one embodiment, the kit further comprises a label or instructions for use in preventing and / or treating a bacterial infection caused by Acinetobacter baumannii in a human, optionally the label or instructions comprising a marketing authorization number (e.g., an FDA or EMA approval number), and optionally the kit comprises an IV or injection device comprising the antibody. Preferably, the antibody is contained in a sealed container.

[0397] Optionally, the kit contains instructions therein for the simultaneous, separate or sequential administration of the therapeutic agents.

[0398] An antibody as defined anywhere herein or a composition as defined anywhere herein may be provided for use as a medicament.

[0399] An antibody as defined anywhere in this specification or a composition as defined anywhere in this specification may be provided for use in a method of treating a bacterial infection caused by Acinetobacter baumannii, the method comprising administering the antibody or composition to a patient.

[0400] An antibody as defined anywhere in the present specification or a composition as defined anywhere in the present specification may be provided for use in a method of preventing a bacterial infection caused by Acinetobacter baumannii, the method comprising administering the antibody or composition to a patient.

[0401] Where an antibody defined anywhere herein that specifically binds to Oxa-23 is administered to a patient, the presence of Oxa-23 may already be confirmed in a sample from that patient, although this is not required.

[0402] When an antibody defined anywhere herein that specifically binds to OC1 LOS is administered to a patient, the presence of OC1 LOS may already be confirmed in a sample from that patient, although this is not required.

[0403] When an antibody defined anywhere herein that specifically binds to KL49 is administered to a patient, the presence of KL49 may already be confirmed in a sample from that patient, although this is not required.

[0404] There is also provided the use of an antibody as defined anywhere herein, or a composition as defined anywhere herein, in the manufacture of a medicament for use in a method of treating a bacterial infection caused by Acinetobacter baumannii.

[0405] There is also provided the use of an antibody as defined anywhere herein, or a composition as defined anywhere herein, in the manufacture of a medicament for use in a method of preventing a bacterial infection caused by Acinetobacter baumannii.

[0406] The present invention provides a method of treating a bacterial infection caused by Acinetobacter baumannii in a patient, the method comprising administering to the patient a therapeutically effective amount of an antibody as defined anywhere herein, or a composition as defined anywhere herein.

[0407] The present invention provides a method of preventing a bacterial infection caused by Acinetobacter baumannii in a patient, the method comprising administering to the patient a therapeutically effective amount of an antibody as defined anywhere herein, or a composition as defined anywhere herein.

[0408] In one embodiment, the bacterial infection caused by Acinetobacter baumannii is a nosocomial bacterial infection caused by Acinetobacter baumannii.

[0409] In one embodiment, the patient has a lower respiratory tract infection, eg, pneumonia.

[0410] In one embodiment, the patient has sepsis.

[0411] In one embodiment, the patient has bacteremia.

[0412] In one embodiment, the method further comprises at least one additional therapeutic agent.

[0413] In one embodiment, the administration of the additional therapeutic agents is simultaneous, separate or sequential.

[0414] In one embodiment, the additional therapeutic agent is at least one, preferably one or two, additional antibodies.

[0415] In one embodiment, the method comprises a first antibody that specifically binds to Oxa-23 and a second antibody that specifically binds to OC1 LOS.

[0416] In one embodiment, the method comprises a first antibody that specifically binds to Oxa-23 and a second antibody that specifically binds to KL49.

[0417] In one embodiment, the method comprises a first antibody that specifically binds to OC1 LOS and a second antibody that specifically binds to KL49.

[0418] In one embodiment, the pharmaceutical composition comprises a first antibody that specifically binds to Oxa-23, a second antibody that specifically binds to OC1 LOS, and a third antibody that specifically binds to KL49.

[0419] In one embodiment, the method further comprises administering a carbapenem.

[0420] In one embodiment, the method further comprises administering colistin.

[0421] Also provided is the use of an antibody as defined anywhere herein for determining the presence or absence of Acinetobacter baumannii in a sample, wherein determining the presence of Acinetobacter baumannii in the sample can be used to diagnose an infection caused by Acinetobacter baumannii in a patient.

[0422] Also provided is a method for determining the presence or absence of Acinetobacter baumannii in a sample, which may include contacting the sample with an antibody as defined anywhere herein and testing for binding between the antibody and Acinetobacter baumannii in the sample, wherein detection of binding indicates the presence of Acinetobacter baumannii in the sample and wherein absence of binding indicates the absence of Acinetobacter baumannii in the sample.

[0423] Also provided is the use of an antibody defined anywhere herein that specifically binds to Oxa-23 to determine the presence or absence of Oxa-23 in a sample. Determining the presence of Oxa-23 in a sample can be used to determine a treatment protocol for the patient. For example, a patient may be identified as a candidate for treatment with an antibody that specifically binds Oxa-23 if Oxa-23 is determined to be present in the patient's sample. The patient may or may not have previously been diagnosed with an Acinetobacter baumannii infection.

[0424] Also provided is the use of an antibody defined anywhere herein that specifically binds to OC1 LOS to determine the presence or absence of OC1 LOS in a sample. Determining the presence of OC1 LOS in a sample can be used to determine a treatment protocol in a patient. For example, a patient may be identified as a candidate for treatment with an antibody that specifically binds to OC1 LOS if the presence of OC1 LOS is determined in the patient's sample. The patient may or may not have already been diagnosed with an Acinetobacter baumannii infection.

[0425] Also provided is the use of an antibody defined anywhere herein that specifically binds to KL49 to determine the presence or absence of KL49 in a sample. Determining the presence of KL49 in a sample can be used to determine a treatment protocol for a patient. For example, a patient may be identified as a candidate for treatment with an antibody that specifically binds to KL49 if the presence of KL49 is determined in the patient's sample. The patient may or may not have already been diagnosed with an Acinetobacter baumannii infection.

[0426] In one embodiment, the antibody is conjugated to a detectable label.

[0427] In one embodiment, the sample is obtained from a human infected with or suspected of being infected with Acinetobacter baumannii. In one embodiment, the sample is obtained from a human infected with or suspected of being infected with Acinetobacter baumannii who exhibits one or more symptoms of a bacterial infection. In one embodiment, the sample is a serum, plasma, or whole blood sample, an oral or nasal swab, urine, feces, or cerebrospinal fluid (CSF), or the sample is derived from an organ or tissue suspected of being infected with Acinetobacter baumannii.

[0428] A diagnostic kit is provided for a use defined anywhere herein or a method defined anywhere herein. The diagnostic kit may comprise an antibody defined anywhere herein and, optionally, one or more buffers. In one embodiment, the diagnostic kit comprises a first reagent comprising an antibody defined anywhere herein and a second reagent comprising a detection molecule that binds to the first reagent. In one embodiment, the detection molecule comprises a detectable label or is an antibody bound to a detectable label. [Brief explanation of the drawings]

[0429] 4. Drawings [Figure 1a] Time-resolved core genome phylogeny of GC2 A. baumannii isolates in the Ho Chi Minh ICU. The shaded area indicates the period during which the carbapenem antibiotic imipenem was used for empirical treatment of VAP in the ICU. Labels A–E represent the five carbapenem-resistant genome subclades in GC2. The capsular K locus subtypes of the 10 strains tested for OMV production are also listed on the right. Marked with an asterisk (*) are the four strains from which OMVs were successfully generated and used to immunize Kymab Intellisellect transgenic mice. [Figure 1b] Scanning electron microscope images of unfixed OMV preparations generated from A. baumannii clinical isolates used for immunization. OMVs were prepared from A. baumannii strains BAL_191, BAL_276, BAL_215, and BAL_084. Approximately 95% of the OMVs in this preparation were 25-70 nm in diameter, with larger OMVs with diameters >80 nm comprising 2% of the preparation. Additionally, amorphous structures could also be observed, comprising 3% of the preparation. [Figure 2a]The regime used for OMV immunization. Ten mice received a prime dose of approximately 1 μg of OMV on day 0 of the study. After this, the mice were divided into two study groups. Five mice from group 1 were sacrificed on day 7, and their spleens and lymph nodes were harvested. Five mice from group 2 received an additional boost immunization on day 36 and were then sacrificed on day 43. Blood was collected before the prime and boost administrations and on day 7. The reactivity of these sera to the immunizing OMVs was assessed by ELISA. B cell responses from organs harvested on day 43 can be analyzed using IntelliSelect screening technology. PB = prebleed; SB = sequential bleeds; TB = terminal bleed. [Figure 2b] Polyclonal serum responses to immunization OMVs from Kymab Intellisellect transgenic mice immunized with a mixed pool of four GC2 A. baumannii OMVs, as determined by ELISA. (a) Kinetics of antigen-specific IgG1 responses to the four GC2 A. baumannii OMVs used for immunization. Total antigen-specific IgG1 responses to the four individual GC2 A. baumannii OMVs used for immunization (BAL_084, BAL_191, BAL_215, and BAL_276, bold) are comparable to responses to two additional GC2 A. baumannii OMVs (BAL_339 and BAL_377) that were not present in the immunization pool on day 43 of the study. Specific IgG1 responses were comparable across all immunized mice, and all human Ig isotypes were represented by specific antibodies present in the polyclonal serum. Antigen-specific relative endpoint titers were calculated relative to a pre-bleed taken before the prime immunization. [Figure 3] Gating strategy for sorting antigen-specific IgG+ B cells from the spleens of GC2 CRAB OMV-immunized mice. [Figure 4a]Sunspot plot of 951 paired VH and VL chain sequences recovered from the spleens of four Kymab Intellisellect transgenic mice immunized with GC2 CRAB OMV. Each VH and VL paired sequence is represented by a circle colored by the individual mouse from which it originated. Sequences within a lineage predicted to be derived from a common B cell precursor are connected by a black line. [Figure 4b] Table showing the number of IgH&L paired sequences, proportional mapping to high quality sequences, and allocation to clusters of related sequences indicative of actively evolving B cell responses to immunogens. [Figure 5a] Comparison of mAb binding to GC2 A. baumannii OMVs and unfixed whole bacterial cells as measured by ELISA. mAbs identified as binders in both ELISA binding assays: mAbs that bound to both unfixed whole GC2 A. baumannii bacterial cells and OMVs at levels above the assay threshold shown in the plot are shown in green. Orange are two mAbs that bound only to unfixed whole bacterial cells. mAbs unable to bind to intact bacterial cell walls are shown in white. [Figure 5b] Selection of mAbs for CHO expression and purification based on their ability to both bind to intact bacterial cell walls and induce C3b deposition, as described above. Examples of selections for subsequent CHO expression are shown in bold. [Figure 7a] Table showing the identified targets of each mAb. Methods used include phylogenetic information gathered from HCI (see above), serological expression cloning using genomic phage libraries (SEC), and Western blot (WB) using specific mAbs. To demonstrate therapeutic efficacy, mAbs in bold (*) were tested in an in vivo challenge model of A. baumannii. [Figure 7b]An example Western blot analysis revealed that the mAb binds to three different targets: a high molecular weight target (KL49 capsule - upper panel), a 10 kD target (OC1 LOS - middle panel), and a 30 kD protein (Oxa-23 - lower panel). DETAILED DESCRIPTION OF THE INVENTION

[0430] 5. Detailed Description of the Invention The present invention provides monoclonal antibodies for the diagnosis and treatment of patients with bacterial infections caused by Acinetobacter baumannii.

[0431] The antibodies described herein are described with respect to the following concepts, aspects, statements, configurations and embodiments: Unless otherwise stated, all concepts, embodiments, statements, configurations and aspects should be read as being combinable with any other concept, aspect, statement, configuration or embodiment unless such combination does not make technical sense or is explicitly stated otherwise. The CDR, VH and VL sequences of the antibodies referred to herein are provided in Table 1.

[0432] 5.1.Definition Unless otherwise defined herein, scientific and technical terms shall have the meanings commonly understood by those of ordinary skill in the art. Further, unless the context otherwise requires, singular terms shall include the plural and plural terms shall include the singular.

[0433] The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Similarly, the word "or" includes "and" unless the context clearly dictates otherwise.

[0434] Although methods and materials similar or equivalent to those described herein can be used to practice or test the present disclosure, suitable methods and compositions are described below. The abbreviation "eg" is derived from the Latin exempli gratia and is used herein to indicate a non-limiting example. Thus, the abbreviation "eg" is synonymous with the term "for example."

[0435] In the present specification and claims, the term "about" is used to modify values ​​and ranges thereof, such as the amount, concentration, volume, process temperature, process time, yield, flow rate, and pressure of a component in a composition, used in describing examples of the present disclosure. The term "about" refers to variations in numerical values ​​that may occur due to approximation considerations, such as typical measuring and handling procedures used to prepare a compound, composition, concentrate, or use formulation; inadvertent errors in these procedures; and differences in the manufacture, source, or purity of starting materials or components used to carry out the method. The term "about" also encompasses amounts that vary with aging of a formulation having a particular initial concentration or mixture, and amounts that vary with mixing or processing of a formulation having a particular initial concentration or mixture. When modified by the term "about," the claims appended hereto include amounts equivalent to these quantities.

[0436] As used herein, "administering" or "administration" refers to the act of injecting or otherwise physically delivering an exogenous substance (e.g., an antibody provided herein, or its encoding nucleic acid, e.g., in an expression vector) to a patient, such as by mucosal, intradermal, intravenous, intramuscular delivery, inhalation, e.g., nebulization, and / or any other physical delivery described herein or known in the art. When an infection or a symptom thereof is being treated, administration of the substance typically occurs after the onset of the infection or a symptom thereof. When an infection or a symptom thereof is being prevented, administration of the substance typically occurs before the onset of the infection or a symptom thereof.

[0437] The terms "antibody," "immunoglobulin," or "Ig" are used interchangeably herein and refer to an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or a combination thereof, via at least one antigen recognition site within the variable region of the immunoglobulin molecule. As used herein, the term "antibody" encompasses intact polyclonal antibodies, intact monoclonal antibodies, antibody fragments (such as Fab, Fab', F(ab')2, and Fv fragments), single-chain Fv (scFv) variants, multispecific antibodies such as bispecific antibodies (including biconjugated antibodies), chimeric antibodies, humanized antibodies, human antibodies, fusion proteins containing an antigenic portion of an antibody, and any other modified immunoglobulin molecule containing an antigen recognition site, so long as the antibody exhibits the desired biological activity. The term "antibody" may also refer to a Y-shaped glycoprotein composed of four polypeptide chains (two light (L) chains and two heavy (H) chains) and having a molecular weight of approximately 150 kDa. There are five mammalian Ig heavy chain isotypes, represented by the Greek letters alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ). Each heavy chain type defines an antibody class: IgA, IgD, IgE, IgG, and IgM. The γ and α classes are further divided into subclasses, e.g., IgG1, hIgG2, mIgG2A, mIgG2B, IgG3, IgG4, IgA1, and IgA2, based on differences in constant domain sequence and function. In mammals, there are two types of immunoglobulin light chains: lambda and kappa. The "variable region" or "variable domain" of an antibody refers to the amino-terminal domain of the antibody's heavy or light chain. The heavy and light chain variable domains may be referred to as "VH" and "VL," respectively. These domains are generally the most variable parts of an antibody (compared to other antibodies of the same class) and contain the antigen-binding site. An example of an antibody is a heavy chain only (ie, H2) antibody, which comprises a dimer of a heavy chain (5'VH-(optional hinge)-CH2-CH3-3') and lacks light chains.

[0438] The antibodies described herein include antibodies that can be oligoclonal, polyclonal, monoclonal (including full-length monoclonal antibodies), camelized, chimeric, CDR-grafted, multispecific, bispecific (including bibinding antibodies), catalytic, chimeric, humanized, fully human, anti-idiotypic, and can be labeled in soluble or conjugated form, as well as fragments, variants, or derivatives thereof, alone or in combination with other amino acid sequences provided by known techniques. Antibodies can be derived from any species. The antibodies described herein can be naked or conjugated to other molecules, such as toxins, radioisotopes, etc.

[0439] The terms "antigen-binding domain," "antigen-binding region," "antigen-binding fragment," and the like refer to the portion of an antibody (e.g., the complementarity-determining region (CDR)) that contains the amino acid residues that interact with an antigen and confer on the binder its specificity and affinity for the antigen. The antigen-binding region can be derived from any animal species, including rodents (e.g., rabbits, rats, or hamsters) and humans. Preferably, the antigen-binding region is of human origin.

[0440] Antigen-binding fragments described herein can include single-chain Fvs (scFvs), single-chain antibodies, single-domain antibodies, domain antibodies, Fv fragments, Fab fragments, F(ab') fragments, F(ab') fragments, antibody fragments exhibiting the desired biological activity, disulfide-stabilized variable regions (dsFvs), dimeric variable regions (diabodies), anti-idiotypic (anti-Id) antibodies (including, for example, anti-Id antibodies against antibodies), intrabodies, linear antibodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments and epitope-binding fragments of any of the above. In particular, antibodies and antibody fragments described herein can include immunoglobulin molecules and immunologically active fragments of immunoglobulin molecules, i.e., molecules containing an antigen-binding site. Digestion of antibodies with the enzyme papain produces two identical antigen-binding fragments, also known as "Fab" fragments, and an "Fc" fragment lacking antigen-binding activity but capable of crystallization. As used herein, "Fab" refers to an antibody fragment containing one constant domain and one variable domain of each of the heavy and light chains. The term "Fc region" is used herein to define the C-terminal region of an immunoglobulin heavy chain, including native-sequence Fc regions and variant Fc regions. "Fc fragment" refers to the carboxy-terminal portions of both H chains held together by disulfides. The effector functions of an antibody are determined by the sequence of the Fc region, which is also recognized by Fc receptors (FcRs) found on certain types of cells. Digestion of an antibody with the enzyme pepsin produces an F(ab')2 fragment, in which the two arms of the antibody molecule remain linked and contain two antigen-binding sites. The F(ab')2 fragment retains the ability to cross-link antigens.

[0441] As used herein, "Fv" refers to the minimum fragment of an antibody that retains both the antigen-recognition and antigen-binding sites. This region consists of a dimer of one heavy-chain variable domain and one light-chain variable domain in tight, non-covalent or covalent association. In this configuration, the three CDRs from each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv containing only three antigen-specific CDRs) has the ability to recognize and bind antigen, albeit with lower affinity than the entire binding site.

[0442] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., an individual antibody comprising the population that is identical except for possible naturally occurring mutations and / or post-translational modifications (e.g., isomerization, amidation), which may be present in minor amounts. Monoclonal antibodies are highly specific and are directed against a single antigenic determinant or epitope. In contrast, polyclonal antibody preparations typically contain different antibodies directed against different antigenic determinants (or epitopes). As used herein, the term "monoclonal antibody" encompasses both intact and full-length monoclonal antibodies, as well as antibody fragments (e.g., Fab, Fab', F(ab'), Fv), single-chain (scFv) variants, fusion proteins containing an antibody portion, and any other modified immunoglobulin molecule containing an antigen-recognition site. Furthermore, "monoclonal antibody" refers to such antibodies produced by a variety of methods, including, but not limited to, hybridoma, phage selection, recombinant expression, and transgenic animals.

[0443] Monoclonal antibodies as used herein include "chimeric" antibodies in which a portion of the heavy and / or light chain is identical to or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain is identical to or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, and fragments of such antibodies, which exhibit the desired biological activity.

[0444] The term "humanized antibody" refers to a subset of chimeric antibodies in which a "hypervariable region" from a non-human immunoglobulin (donor antibody) substitutes residues from a hypervariable region of a human immunoglobulin (recipient antibody). Generally, a humanized antibody will comprise substantially all of at least one, and usually two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin sequence and all or substantially all of the framework regions are those of a human immunoglobulin sequence, although the framework regions may contain one or more substitutions which improve antibody performance, such as binding affinity, isomerization, immunogenicity, etc.

[0445] The terms "hypervariable region," "CDR region," or "CDR" refer to the regions of an antibody variable domain that are hypervariable in sequence and / or form structurally defined loops. Generally, the antigen-binding site of an antibody contains six hypervariable regions: three in the VH (CDRH1, CDRH2, CDRH3) and three in the VL (CDRL1, CDRL2, CDRL3). These regions of the antibody heavy and light chains confer antigen-binding specificity to the antibody. CDRs can be defined according to the Kabat system (Kabat, E.A. et al., 1991, "Sequences of Proteins of Immunological Interest," 5th edition, NIH Publication no. 91-3242, USDapartment of Health and Human Services). Other systems may be used to define CDRs, such as the system devised by Chothia et al. (see Chothia, C. & Lesk, AM, 1987, "Canonical structures for the hypervariable regions of immunoglobulins", J. Mol. Biol., 196, 901-917) and the IMGT system (see Lefranc, MP, 1997, "Unique database numbering system for immunogenetic analysis", Immunol. Today, 18, 50). Antibodies typically contain three heavy chain CDRs and three light chain CDRs. The term CDR is used herein to refer to one or several of these regions. Those skilled in the art can easily compare different nomenclature systems and determine whether a particular sequence can be defined as a CDR.

[0446] A "human antibody" is an antibody having an amino acid sequence corresponding to that of an antibody produced by a human and / or made using any of the techniques for making human antibodies, specifically excluding humanized antibodies containing non-human antigen-binding residues. The term "specifically binds" refers to a measurable and reproducible interaction, such as binding between a target and an antibody, that determines the presence of the target in the presence of a heterogeneous population of molecules, including biomolecules. For example, an antibody that specifically binds to a target (which may be an epitope) is an antibody that binds to this target with higher affinity, avidity, more readily, and / or for a longer period of time than it binds to other targets. In one example, the extent of binding of the antibody to an unrelated target is less than about 10% of the binding of the antibody to the target, as measured, for example, by radioimmunoassay (RIA).

[0447] As used herein, "approval number" or "marketing authorization number" refers to a number issued by a regulatory agency when the regulatory agency determines that a particular medical product and / or composition may be sold and / or offered for sale within that agency's jurisdiction. As used herein, "regulatory agency" refers to, for example, one of the agencies responsible for evaluating the safety and effectiveness of medical products and / or compositions and controlling the sale / marketing of such products and / or compositions in a given territory. The Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EPA) in Europe are just two examples of such regulatory agencies. Other non-limiting examples include the SDA, MPA, MHPRA, IMA, ANMAT, Hong Kong Department of Health-Drug Office, CDSCO, Medsafe, and KFDA.

[0448] As used herein, the term "carrier" refers to a diluent, adjuvant (e.g., Freund's adjuvant (complete and incomplete)), excipient, or vehicle used in administering a therapeutic agent. Such pharmaceutical carriers can be sterile liquids, such as water and oils, such as those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. Water is a preferred carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions.

[0449] As used herein, the term "composition" is intended to encompass a product containing specified ingredients (e.g., antibodies), optionally in specified amounts, as well as any product resulting directly or indirectly from the combination of specified ingredients, optionally in specified amounts.

[0450] As used herein, the terms "comprising" or "comprises" are used in reference to antibodies, uses, compositions, methods, and their respective components that are essential to the methods or compositions of the invention, but are open to including non-specified elements (whether essential or not).

[0451] The term "consisting of" refers to the antibodies, uses, compositions, methods, and each component thereof described herein, excluding any element not recited in the description of the example.

[0452] As used herein, the term "consisting essentially of" refers to elements required for a given example. The term permits the presence of elements that do not materially affect the basic and novel or functional characteristics of the example.

[0453] An "effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired effect (including therapeutic or prophylactic results). A "therapeutically effective amount" refers to the minimum concentration necessary to bring about measurable improvement or prevention of a particular disorder. A therapeutically effective amount may vary depending on factors such as the patient's infection status, age, sex, and weight, and the ability of the antibody to elicit a desired response in an individual. A therapeutically effective amount is also an amount in which the therapeutically beneficial effects outweigh any toxic or harmful effects of the antibody. A "prophylactically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. In some examples, an effective amount of an antibody is from about 0.1 mg / kg (mg of antibody per kg of subject body weight) to about 100 mg / kg. In particular examples, an effective amount of an antibody provided herein is about 0.1 mg / kg, about 0.5 mg / kg, about 1 mg / kg, about 3 mg / kg, 5 mg / kg, about 10 mg / kg, about 15 mg / kg, about 20 mg / kg, about 25 mg / kg, about 30 mg / kg, about 35 mg / kg, about 40 mg / kg, about 45 mg / kg, about 50 mg / kg, about 60 mg / kg, about 70 mg / kg, about 80 mg / kg, about 90 mg / kg, or about 100 mg / kg (or within these ranges). In some examples, "effective amount," as used herein, also refers to the amount of an antibody that achieves a particular result (e.g., induces complement activation).

[0454] As used herein, the term "epitope" refers to a localized region on an antigen or antigen surface having immunogenic activity that can bind to one or more antigen-binding regions of an antibody and elicit an immune response in an animal, preferably a mammal, and most preferably a human. An epitope with immunogenic activity is a portion of an antigen (e.g., a polypeptide, carbohydrate, or lipid molecule) that elicits an antibody response in an animal. An epitope with antigenic activity is a portion of an antigen to which an antibody specifically binds, as determined by any method well known in the art, such as the immunoassays described herein. An antigenic epitope need not necessarily be immunogenic. Epitopes usually consist of chemically active surface groupings of molecules, such as amino acids or sugar side chains, and possess specific three-dimensional structural characteristics as well as specific charge characteristics. The region of a polypeptide that contributes to an epitope can be contiguous amino acids of the polypeptide, or an epitope can be formed by the assembly of two or more non-contiguous regions of the polypeptide. An epitope may or may not be a three-dimensional surface feature of an antigen. As described elsewhere herein, competition between antibodies can also be determined, for example, using SPR.

[0455] The term "excipient," as used herein, refers to an inert substance commonly used as a diluent, vehicle, preservative, binder, or stabilizer for a drug, and includes, but is not limited to, proteins (e.g., serum albumin, etc.), amino acids (e.g., aspartic acid, glutamic acid, lysine, arginine, glycine, histidine, etc.), fatty acids and phospholipids (e.g., alkylsulfonates, caprylates, etc.), surfactants (e.g., SDS, polysorbates, nonionic surfactants, etc.), sugars (e.g., sucrose, maltose, trehalose, etc.), and polyols (e.g., mannitol, sorbitol, etc.). See also Remington's Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, Pa., which is incorporated herein by reference in its entirety.

[0456] The term "heavy chain," when used in reference to antibodies, refers to five different types, designated alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ), based on the amino acid sequence of the heavy chain constant domain. These different types of heavy chains are well known and give rise to five classes of antibodies: IgA, IgD, IgE, IgG, and IgM, including two subclasses of IgA, IgA1 and IgA2, and four subclasses of IgG, IgG1, IgG2, IgG3, and IgG4. Preferably, the heavy chain is a human heavy chain. In the human population, multiple heavy chain constant region alleles exist for each immunoglobulin or immunoglobulin subclass. The nucleotide and amino acid sequences of these allelic variants are accessible in publicly available databases, such as IMGT, ENSEMBL Swiss-Prot, and Uniprot. Allelic variants can also be identified in various genome sequencing projects. In one example, an antibody disclosed herein comprises a heavy chain encoded by an IgG1 constant region allele, including, but not limited to, human IGHG1*01, IGHG1*02, IGHG1*03, IGHG1*04, and IGHG1*05 (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). In one example, an antibody disclosed herein comprises a protein encoded by an IgG4 constant region allele, including, but not limited to, human IGHG4*01, IGHG4*02, IGHG4*03, and IGHG4*04 (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). In another example, the heavy chain is an IgA isotype, human IgA1 or human IgA2, exemplary amino acid sequences of which are shown in Table 2. In another example, the heavy chain is a neutralized IgG isotype, such as neutralized IgG4. In a particular example, the antibody comprises a human gamma 4 constant region. In another example, the heavy chain constant region does not bind to Fc-γ receptors and contains, for example, a Leu235Glu mutation. In another example, the heavy chain constant region contains a Ser228Pro mutation to increase stability. In another example, the heavy chain constant region is IgG4-PE.In another example, the antibodies disclosed herein comprise a heavy chain constant region encoded by a mouse IgG1 constant region allele, including, but not limited to, mouse IGHG1*01 or IGHG1*02.

[0457] The term "host", as used herein, refers to an animal, preferably a mammal, and most preferably a human.

[0458] As used herein, the term "host cell" refers to a particular subject cell transfected with a nucleic acid molecule, and the progeny or potential progeny of such a cell. The progeny of such a cell may not be identical to the parent cell transfected with the nucleic acid molecule due to mutations or environmental influences that may occur in subsequent generations or in the integration of the nucleic acid molecule into the host cell genome.

[0459] The term "in combination" in the context of the administration of other treatments refers to the use of two or more treatments. The use of the term "in combination" does not limit the order in which treatments are administered to an infected subject. A first treatment can be administered before (e.g., 1 minute, 45 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), simultaneously with, or after (e.g., 1 minute, 45 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the second treatment is administered to the subject. Any additional therapy can be administered in any order with the other additional therapies. In certain instances, the antibody can be administered in combination with one or more treatments.

[0460] As used herein, "injection device" refers to a device designed to perform injections, which includes temporarily fluidly connecting the injection device to human tissue, usually subcutaneous tissue. Furthermore, injection includes administering a quantity of liquid medication into the tissue and disconnecting or removing the injection device from the tissue. In some examples, the injection device may be an intravenous or IV device, which is a type of injection device used when the target tissue is blood in the circulatory system, e.g., blood in a vein. A common, but non-limiting, example of an injection device is a needle and a syringe.

[0461] As used herein, "instructions" refers to written, printed, or graphical indication of contents on an article's immediate container, e.g., written markings on a vial containing a pharmaceutically active agent, or details of the composition and use of a product of interest included in a kit containing the composition of interest. The instructions describe a method of treatment that is intended to be performed or carried out.

[0462] An "isolated" or "purified" antibody or protein is one that has been identified, separated, and / or recovered from components of its production environment (e.g., natural or recombinant). For example, the antibody or protein is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the antibody is derived, or, if chemically synthesized, substantially free of chemical precursors or other chemicals. The term "substantially free of cellular material" includes preparations of antibodies in which the antibody is separated from cellular components of the cells from which it is isolated or recombinantly produced. Thus, an antibody that is substantially free of cellular material includes preparations of antibodies that contain less than about 30%, 20%, 10%, or 5% (by dry weight) of heterologous protein (also referred to herein as "contaminating protein"). If the antibody is recombinantly produced, it is also preferably substantially free of culture medium; i.e., culture medium represents less than about 20%, less than about 10%, or less than about 5% of the volume of the protein preparation. When an antibody is produced by chemical synthesis, it is preferably substantially free of chemical precursors or other chemicals, i.e., separated from chemical precursors or other chemicals involved in protein synthesis. Thus, such preparations of antibodies contain less than about 30%, 20%, 10%, or 5% (by dry weight) of chemical precursors or compounds other than the antibody of interest. In preferred examples, the antibody is isolated or purified.

[0463] Terms such as "Kabat numbering" are recognized in the art and refer to a numbering system for amino acid residues that are more variable (i.e., hypervariable) than other amino acid residues in an antibody heavy chain variable region or antigen-binding portion thereof (Kabat et al., (1971) Ann. NY Acad. Sci., 190:382-391 and Kabat et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, USDapartment of Health and Human Services, NIH Publication No. 91-3242). In the heavy chain variable region, the hypervariable regions typically range from amino acid positions 31 to 35 in CDR1, amino acid positions 50 to 65 in CDR2, and amino acid positions 95 to 102 in CDR3.

[0464] As used herein, "label" or "labeled" refers to the addition of a detectable moiety to a polypeptide, such as a radioactive label, a fluorescent label, an enzyme label, a chemiluminescent label, or a biotinyl group or gold. Radioisotopes or radionuclides include H, C, N, S, Y, Tc, In, I, I; fluorescent labels include rhodamine, lanthanide fluorophores, or FITC; enzyme labels may include horseradish peroxidase, β-galactosidase, luciferase, and alkaline phosphatase.Additional labels include, by way of example and not limitation, enzymes such as glucose-6-phosphate dehydrogenase ("G6PDH"), alpha-D-galactosidase, glucose oxidase, glucose amylase, carbonic anhydrase, acetylcholinesterase, lysozyme, malate dehydrogenase, and peroxidase; dyes (e.g., cyanine dyes, such as Cy5™, Cy5.5™, or Cy7™); additional fluorescent labels or fluorophores, such as fluorescein and its derivatives, fluorescent dyes, GFP (GFP stands for "green fluorescent protein"), other fluorescent proteins (e.g., mCherry, mTomato), dansyl, umbelliferone, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde, and fluorescamine; fluorescent dyes, such as lanthanide cryptates and chelates, such as europium (Perkin Elmer and Cisbio Assays); chemiluminescent labels or chemiluminescers, such as isoluminol, luminol, and dioxetanes; sensitizers; coenzymes; enzyme substrates; particles, such as latex or carbon particles; metal sols; microcrystals; liposomes; cells, etc. (which may be further labeled with dyes, catalysts, or other detectable groups); molecules, such as biotin, digoxigenin, or 5-bromodeoxyuridine; toxin moieties, such as a toxin moiety selected from the group consisting of Pseudomonas exotoxin (PE or a cytotoxic fragment or variant thereof), diphtheria toxin or a cytotoxic fragment or variant thereof, botulinum toxin A, B, C, D, E, or F, ricin or a cytotoxic fragment thereof, such as ricin A, abrin or a cytotoxic fragment thereof, saporin or a cytotoxic fragment thereof, pokeweed antiviral toxin or a cytotoxic fragment thereof, and bryodin 1 or a cytotoxic fragment thereof.

[0465] The term "light chain," when used with respect to an antibody, refers to an immunoglobulin light chain, of which there are two types in mammals: lambda (λ) and kappa (κ). The light chain is preferably a human light chain. The light chain constant region is preferably a human constant region. Multiple light chain constant region alleles exist in the human population. The nucleotide and amino acid sequences of these allelic variants are accessible in publicly available databases such as IMGT, ENSEMBL Swiss-Prot, and Uniprot. In one example, the antibodies disclosed herein include proteins encoded by human kappa constant region alleles, including, but not limited to, IGKC*01, IGKC*02, IGKC*03, IGKC*04, and IGKC*05 (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). In one example, the antibodies disclosed herein include proteins encoded by human lambda constant region alleles, including, but not limited to, IGLC1*01, IGLC1*02, IGLC2*01, IGLC2*02, IGLC2*03, IGLC3*01, IGLC3*02, IGLC3*03, IGLC3*04, IGLC6*01, IGLC7*01, IGLC7*02, and IGLC7*03 (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). In another example, an antibody disclosed herein comprises a light chain constant region encoded by a mouse kappa constant region allele, including, but not limited to, IGKC*01, IGKC*03, or IGKC*03 (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). In another example, an antibody disclosed herein comprises a light chain constant region encoded by a mouse lambda constant region allele, including, but not limited to, IGLC1*01, IGLC2*01, or IGLC3*01 (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0466] "Percent (%) amino acid sequence identity" with respect to a peptide, polypeptide, or antibody sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical with amino acid residues in a particular peptide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, without considering conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be accomplished in a variety of ways within the skill of the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEG ALIGN™ (DNASTAR) software. In one embodiment, the percent identity is about 70%. In one embodiment, the percent identity is about 75%. In one embodiment, the percent identity is about 80%. In one embodiment, the percent identity is about 85%. In one embodiment, the percent identity is about 90%. In one embodiment, the percent identity is about 92%. In one embodiment, the percent identity is about 95%. In one embodiment, the percent identity is about 97%. In one embodiment, the percent identity is about 98%. In one embodiment, the percent identity is about 99%. In one embodiment, the percent identity is 100%.

[0467] The terms "naturally-occurring" or "natural" when used in reference to biological material such as a nucleic acid molecule, polypeptide, host cell, etc., refer to something that is found in nature and has not been manipulated by human beings.

[0468] As used herein, "packaging" refers to the manner in which components are grouped and / or secured together into a unit suitable for distribution and / or use. Packaging can include, for example, boxes, bags, syringes, ampoules, vials, tubes, clamshell packages, barriers and / or containers to maintain sterility, labeling, etc.

[0469] As used herein, the term "pharmaceutically acceptable," as used herein in reference to a pharmaceutical composition, means approved by a state or federal regulatory agency or listed in the US Pharmacopeia, the European Pharmacopeia, or other generally recognized pharmacopoeias for use in animals, particularly humans.

[0470] As used herein, the terms "polynucleotide," "nucleotide," "nucleic acid," "nucleic acid molecule," and other similar terms are used interchangeably and include DNA, RNA, mRNA, and the like.

[0471] As used herein, "prevent," "preventing," and "prevention" refer to the total or partial inhibition of the progression, recurrence, onset, or spread of an infection resulting from the administration of a therapy or combination of therapies (e.g., a combination of prophylactic or therapeutic agents such as antibodies) provided herein.

[0472] The term "soluble" refers to a polypeptide that lacks one or more transmembrane or cytoplasmic domains found in its native or membrane-bound form. In one example, a "soluble" form of a polypeptide lacks both a transmembrane domain and a cytoplasmic domain.

[0473] The term "subject" or "patient" refers to any animal, including, but not limited to, mammals. As used herein, the term "mammal" refers to a vertebrate that either suckles its young and gives birth to live young (eutherian or placental mammals) or lays eggs (metatherian or non-placental mammals). Examples of mammalian species include, but are not limited to, humans and other primates, including non-human primates such as chimpanzees, other ape and monkey species; livestock, including cattle, sheep, pigs, goats, and horses; domestic mammals, including dogs and cats; laboratory animals, including rodents, such as mice, rats (e.g., cotton rats), and guinea pigs; and birds, including domestic, wild, and game birds, including chickens, turkeys, and other poultry, ducks, geese, and the like.

[0474] When used in the present specification, "substantially all" refers to at least 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or about 100%.

[0475] The term "surfactant" as used herein refers to organic substances with an amphiphilic structure. That is, they are composed of groups with opposite solubility tendencies, typically an oil-soluble hydrocarbon chain and a water-soluble ionic group. Depending on the charge of the surface-active moiety, surfactants can be classified as anionic, cationic, and nonionic surfactants. Surfactants are often used as wetting agents, emulsifiers, solubilizers, and dispersants in the preparation of various pharmaceutical compositions and biological materials.

[0476] As used herein, the term "tag" refers to any type of moiety attached to a polynucleotide encoding, for example, a polypeptide and / or antibody as described herein. For example, a polynucleotide encoding an antibody described herein can contain one or more additional tag-encoding nucleotide sequences that encode, for example, a detectable moiety or a moiety that aids in affinity purification. When translated, the tag and antibody can be in the form of a fusion protein. The term "detectable" or "detection" with respect to a tag refers to any tag that can be visualized or whose presence can be determined and / or measured in other ways (e.g., by quantification). A non-limiting example of a detectable tag is a fluorescent tag.

[0477] As used herein, the term "therapeutic agent" refers to any agent that can be used to treat, manage, or ameliorate a bacterial infection caused by Acinetobacter baumannii and / or one or more symptoms associated therewith. In certain instances, the term "therapeutic agent" refers to an antibody. In certain other instances, the term "therapeutic agent" refers to an agent other than an antibody. Preferably, a therapeutic agent is an agent that is known to be, has been used in the past, or is currently being used to treat, manage, or ameliorate a bacterial infection caused by Acinetobacter baumannii and / or one or more symptoms associated therewith.

[0478] As used herein, the term "therapy" refers to any protocol, method, and / or agent that can be used to prevent, manage, treat, and / or ameliorate a bacterial infection caused by Acinetobacter baumannii. In certain instances, the term "therapy" refers to biologic, supportive, and / or other therapies useful in the prevention, management, treatment, and / or amelioration of a bacterial infection caused by Acinetobacter baumannii known to those of skill in the art, such as healthcare professionals.

[0479] The terms "treat," "treatment," and "treating" refer to the reduction or amelioration of the progression, severity, and / or duration of a bacterial infection caused by Acinetobacter baumannii resulting from the administration of one or more therapies (including, but not limited to, the administration of one or more prophylactic or therapeutic agents, such as antibodies). In certain instances, such terms refer to the reduction in bacterial load and / or the suppression or alleviation of one or more symptoms associated with a bacterial infection caused by Acinetobacter baumannii. The reduction in bacterial load can be measured by counting cultured bacterial colonies on nutrient agar plates after plating of organ homogenates. IL-6 levels are measured by ELISA.

[0480] The terms "variable region" or "variable domain" refer to portions of the light and heavy chains, typically the amino-terminal 120-130 amino acids of the heavy chain and approximately 100-110 amino acids of the light chain, which vary significantly in sequence among antibodies and are used to determine the binding and specificity of each particular antibody for its specific antigen. Sequence variability is concentrated in regions called complementarity-determining regions (CDRs), while the more conserved regions within the variable domain are called framework regions (FRs). CDRs are primarily responsible for antibody-antigen interactions. The numbering of amino acid positions used herein is according to IMGT (Lefranc MP, "IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains," Dev. Comp. Immunol. 27(1):55-77 (2003)). In a preferred example, the variable region is a human variable region.

[0481] Definitions of common terms in cell biology and molecular biology can be found in "The Merck Manual of Diagnosis and Therapy", 19th Edition, published by Merck Research Laboratories, 2006 (ISBN 0-911910-19-0); Robert S. Porter et al. (eds.), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0-632-02182-9); Benjamin Lewin, Genes X, published by Jones & Bartlett Publishing, 2009 (ISBN-10:0763766321); Kendrew et al. (Eds.), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8) and Current Protocols in Protein Sciences 2009, Wiley Intersciences, Coligan et al., eds.

[0482] Unless otherwise specified, this disclosure includes, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual (4ed.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA (2012); Davis et al., Basic Methods in Molecular Biology, Elsevier Science Publishing, Inc., New York, USA (1995); or Methods in Enzymology: Guide to Molecular Cloning Techniques. Vol.152, SLBerger and ARKimmel Eds., Academic Press Inc., San Diego, USA (1987); Current Protocols in Protein Science (CPPS) (John E. Coligan, et al., ed., John Wiley and Sons, Inc.), Current Protocols in Cell Biology (CPCB) (Juan S. Bonifacino et al., ed., John Wiley and Sons, Inc.) and Culture of Animal Cells: A Manual of Basic Technique by Standard procedures were performed as described in R. Ian Freshney, Publisher: Wiley-Liss; 5th edition (2005), Animal Cell Culture Methods (Methods in Cell Biology, Vol. 57, Jennie P. Mather and David Barnes editors, Academic Press, 1st edition, 1998) (all of which are incorporated herein by reference in their entirety).

[0483] Other terms are defined herein within the description of various examples of the present disclosure.

[0484] In the disclosure herein relating to antibodies defined by an antibody sequence, the antibody sequence may be defined by reference to an internal antibody reference number or SEQ ID NO. A disclosure herein reciting an internal antibody reference number should also be considered a disclosure of the same subject matter if the sequence defined by the internal antibody reference number is replaced by the corresponding SEQ ID NO.

[0485] 5.2 Anti-Oxa-23 antibody The antibodies of the invention bind to Oxa-23 on the surface of intact bacteria (ie, with an unruptured membrane / cell wall), eg, on live bacteria.

[0486] The Oxa-23 carbapenemase enzyme is a 30 kD protein expressed by the oxa-23 gene. Oxa-23 is a class D β-lactamase, a major group of enzymes involved in resistance to carbapenem antibiotics (Docquier JD, Mangani S. Structure-Function Relationship of Class D Carbapenemases. Curr Drug Targets. 2016;17(9):1061-71. doi:10.2174 / 1389450116666150825115824. PMID:26302798. (The contents of which are incorporated herein by reference)).

[0487] The Oxa-23 gene, which encodes the Oxa-23 carbapenemase enzyme, is widely distributed among clinical isolates of Acinetobacter baumannii and reduces the efficacy of treatment with carbapenem antibiotics.

[0488] The sequence of the wild-type Oxa-23 enzyme is provided under GenBank accession number AJ132105.1 and is as follows: [ka] As shown in.

[0489] Identifying mAbs that bind to Oxa-23 is crucial. We unexpectedly found that Oxa-23 can be targeted by antibodies or closely related antibodies in the Acinetobacter baumannii cell membrane, a previously unknown targeting site. In other words, we unexpectedly discovered that the Oxa-23 enzyme is a membrane protein present on the surface of living bacteria. Furthermore, we unexpectedly found that antibodies that block the enzymatic function of Oxa-23 can be used to sensitize Acinetobacter baumannii to carbapenems. Furthermore, we unexpectedly found that the Oxa-23-binding epitope is highly conserved across G2 clonal strains of Acinetobacter baumannii. Notably, its binding epitope appears to be conserved across at least 60% of G2 clonal strains of Acinetobacter baumannii. Therefore, the present invention demonstrates that targeting the Oxa-23 enzyme is a highly attractive target for antibody-based diagnostics and therapeutics of Acinetobacter baumannii. In other words, antibodies targeting Oxa-23 on the surface of live bacteria can be considered pan-Acinetobacter baumannii antibodies.

[0490] Therefore, antibodies of the present invention that specifically bind to Oxa-23 are highly important for the diagnosis of infections caused by Acinetobacter baumannii and for the treatment of infections caused by Acinetobacter baumannii in patients, particularly in patients in whom Oxa-23 is known to be present.

[0491] Until the present invention, Oxa-23 was widely thought to be associated with the bacterial periplasm and had not been considered a potential antibody target on the bacterial surface. (Chiu CH, Liu YH, Wang YC, Lee YT, Kuo SC, Chen TL, Lin JC, Wang FD. In vitro activity of SecA inhibitors in combination with carbapenems against carbapenem-hydrolyzing class D β-lactamase-producing Acinetobacter baumannii. J Antimicrob Chemother. 2016 Dec;71(12):3441-3448. doi:10.1093 / jac / dkw331. Epub 2016 Aug 19. PMID:27543656, the contents of which are incorporated herein by reference.) This target was only unexpectedly identified and validated by the methodology used by the inventors to discover the antibody.

[0492] In particular examples, the antibody is a fully human antibody, such as a fully human monoclonal antibody.

[0493] Antibody 1348 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 21, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 22, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 23, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 24. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 20. Antibody 1348 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 26, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 27, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 28, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 29. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 25. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0494] Antibody 1349 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 31, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 32, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 33, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 34. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 30. Antibody 1349 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 36, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 37, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 28, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 38. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 35. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). In one embodiment, the heavy chain constant region sequence is SEQ ID NO: 418. In one embodiment, the light chain constant region sequence is SEQ ID NO: 448. In one embodiment, the antibody comprises a heavy chain comprising a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 31 and a heavy chain constant region amino acid sequence of SEQ ID NO: 418. In one embodiment, the antibody comprises a light chain comprising a light chain variable region (VL) amino acid sequence of SEQ ID NO: 36 and a light chain constant region amino acid sequence of SEQ ID NO: 448. In one embodiment, the antibody is antibody 1349. Antibody 1349 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 31, a heavy chain constant region amino acid sequence of SEQ ID NO: 418, a light chain variable region (VL) amino acid sequence of SEQ ID NO: 36, and a light chain constant region amino acid sequence of SEQ ID NO: 448. Antibody 1540 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 21, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 22, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 23, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 24. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 20. Antibody 1540 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 26, with a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 27, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 28, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 29.The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 25. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0495] Antibody 1548 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 172, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 173, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 174. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 171. Antibody 1548 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 176, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 149, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 177, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 178. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 175. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0496] Antibody 1550 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 180, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 181, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 173, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 182. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 179. Antibody 1550 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 184, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 185, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 28, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 186. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 183. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0497] 5.3 Anti-OC1 LOS antibody The antibodies of the present invention bind to OC1 LOS on the surface of intact bacteria (ie, with an unruptured membrane / cell wall), eg, on live bacteria.

[0498] Bacterial lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are unique, complex glycolipids that provide characteristic components of the outer membrane of Gram-negative bacteria. LPS and LOS contain a core oligosaccharide combined with repeating sugar units that extend from the cell surface. LPS and LOS constitute the protective barrier known to line the bacterial wall.

[0499] Until the present invention, such LPS and LOS had not been considered as potential antibody targets on bacterial surfaces due to their structural and antigenic diversity, in part due to work performed on the KDO glycomolecule, a target that was only unexpectedly identified and validated by the methodology used by the inventors to discover antibodies.

[0500] OC1 LOS is a 10 kD lipooligosaccharide expressed by the OC1 gene. Details of its structure can be found in Kenyon JJ, Nigro SJ, Hall RM. Variation in the OC locus of Acinetobacter baumannii genomes predicts extensive structural diversity in the lipooligosaccharide. PLoS ONE. 2014 Sep 23;9(9):e107833. doi:10.1371 / journal.pone.0107833. PMID:25247305; PMCID:PMC4172580 (the contents of which are incorporated herein by reference).

[0501] We unexpectedly discovered that the OC1 LOS not only serves as a target for diagnostic and therapeutic antibodies, but also that its binding epitope is highly conserved across the G2 clonal strains of Acinetobacter baumannii. In particular, the binding epitope appears to be conserved across at least 70% of the G2 clonal strains of Acinetobacter baumannii. Therefore, targeting the OC1 LOS is highly attractive as a target for antibody-based diagnostics and therapeutics for Acinetobacter baumannii. In other words, antibodies targeting the OC1 LOS on the surface of live bacteria can be considered pan-Acinetobacter baumannii antibodies.

[0502] Without wishing to be bound by theory, it is believed that the antibodies of the present invention bind to the core oligosaccharide of OC1 LOS.

[0503] The antibodies of the present invention that specifically bind to OC1 LOS are of great importance for the diagnosis of infections caused by Acinetobacter baumannii and for the treatment of infections caused by Acinetobacter baumannii in patients, particularly in patients known to have OC1 LOS.

[0504] In particular examples, the antibody is a fully human antibody, such as a fully human monoclonal antibody.

[0505] Antibody 1042 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 188, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 32, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 33, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 189. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 187. Antibody 1042 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 191, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 37, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 28, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 192. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 190. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0506] Antibody 1043 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 194, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 195, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 33, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 196. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 193. Antibody 1043 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 198, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 37, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 9, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 199. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 197. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0507] Antibody 1403 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 88, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 22, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 89, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 90. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 87. Antibody 1403 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 92, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 93, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 28, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 94. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 91. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0508] Antibody 1405 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 103, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 104, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 33, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 105. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 102. Antibody 1405 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 107, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 27, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 28, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 108. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 106. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0509] Antibody 1407 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 110, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 111, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 33, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 112. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 109. Antibody 1407 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 114, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 115, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 28, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 116. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 113. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0510] Antibody 1408 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 118, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 104, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 33, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 119. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 117. Antibody 1408 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 121, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 122, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 28, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 123. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 120. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0511] Antibody 1413 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 144, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 145, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 33, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 146. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 143. Antibody 1413 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 148, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 149, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 150, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 151. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 147. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0512] 5.4 Anti-KL49 antibody The antibodies of the present invention bind to KL49 on the surface of intact bacteria (ie, with an unruptured membrane / cell wall), eg, on live bacteria.

[0513] KL49 is produced by A. baumannii strains and is a form of capsular polysaccharide (CPS) that surrounds the cell outer membrane. CPS is a densely packed, high-molecular-weight carbohydrate composed of repeating oligosaccharide units that provides a barrier against environmental stressors, resistance to antimicrobial compounds, and immunological defense mechanisms.

[0514] The structure of the KL49 capsular antigen is described in Singh JK, Adams FG, Brown MH. Diversity and Function of Capsular Polysaccharide in Acinetobacter baumannii Front Microbiol.2019 Jan 9;9-3301.doi:10.3389 / fmicb.2018.03301.PMID:30687280;PMCID:PMC6333632, the contents of which are incorporated herein by reference.

[0515] The presence of the KL49 capsule is associated with high virulence and increased mortality, and Acinetobacter baumannii KL49 has now emerged as the dominant clone in Southeast Asia (Zhou K, Tang X, Wang L, Guo Z, Xiao S, Wang Q, Zhuo C. An Emerging Clone (ST457) of Acinetobacter baumannii Clonal Complex 92 With Enhanced Virulence and Increasing Endemicity in South China. J Infect Dis. 2018 Nov 13;67(suppl_2):S179-S188. doi:10.1093 / cid / ciy691. PMID:30423046, all of which are incorporated herein by reference). Therefore, our discovery that the KL49 protein is present on the surface of live bacteria and can be targeted by diagnostic and therapeutic antibodies is of great value in enabling early diagnosis and treatment of these patients.

[0516] Therefore, the antibodies of the present invention that specifically bind to KL49 are highly important for the diagnosis of infections caused by Acinetobacter baumannii and for the treatment of infections caused by Acinetobacter baumannii in patients, particularly in patients in which KL49 is known to be present.

[0517] In particular examples, the antibody is a fully human antibody, such as a fully human monoclonal antibody.

[0518] Antibody 1345 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 2, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 4, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 5. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 1. Antibody 1345 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 7, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 8, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 9, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 10. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 6. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0519] Antibody 1347 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 12, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 14. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 11. Antibody 1347 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 16, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 19. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 15. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0520] Antibody 1350 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 40, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 41. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 39. Antibody 1350 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 16, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 19. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 42. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0521] Antibody 1351 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 44, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 45. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 43. Antibody 1351 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 47, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 10. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 46. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0522] Antibody 1363 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 49, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 50. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 48. Antibody 1363 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 52, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 19. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 51. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0523] Antibody 1364 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 54, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 55. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 53. Antibody 1364 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 57, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 58, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 59. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 56. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0524] Antibody 1397 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 61, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 62. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 60. Antibody 1397 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 64, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 59. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 63. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0525] Antibody 1398 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 66, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 67. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 65. Antibody 1398 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 69, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 59. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 68. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0526] Antibody 1400 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 71, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 72. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 70. Antibody 1400 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 74, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 59. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 73. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0527] Antibody 1401 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 76, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 77. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 75. Antibody 1401 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 79, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 80. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 78. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0528] Antibody 1402 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 82, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 83. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 81. Antibody 1402 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 85, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 86. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 84. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are shown in Table 2).

[0529] Antibody 1404 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 96, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 97, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 98. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 95. Antibody 1404 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 100, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 101, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 59. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 99. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0530] Antibody 1409 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 125, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 126. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 124. Antibody 1409 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 128, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 129. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 127. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0531] Antibody 1410 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 131, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 132. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 130. Antibody 1410 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 134, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 135. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 133. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0532] Antibody 1412 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 137, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 138, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 139. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 136. Antibody 1412 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 141, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 142, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 86. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 140. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0533] Antibody 1414 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 153, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 154, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 155, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 156. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 152. Antibody 1414 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 158, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 159. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 157. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0534] Antibody 1415 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 161, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 162, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 163. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 160. Antibody 1415 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 165, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 135. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 164. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2).

[0535] Antibody 1416 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 167, comprising a CDRH1 amino acid sequence (IMGT) of SEQ ID NO: 3, a CDRH2 amino acid sequence (IMGT) of SEQ ID NO: 13, and a CDRH3 amino acid sequence (IMGT) of SEQ ID NO: 168. The heavy chain nucleic acid sequence of the VH domain is SEQ ID NO: 166. Antibody 1416 has a light chain variable region (VL) amino acid sequence of SEQ ID NO: 170, comprising a CDRL1 amino acid sequence (IMGT) of SEQ ID NO: 17, a CDRL2 amino acid sequence (IMGT) of SEQ ID NO: 18, and a CDRL3 amino acid sequence (IMGT) of SEQ ID NO: 10. The light chain nucleic acid sequence of the VL domain is SEQ ID NO: 169. The VH domain can be combined with any of the heavy chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). The VL domain can be combined with any of the light chain constant region sequences described herein (the nucleotide and corresponding amino acid sequences of which are set forth in Table 2). In one embodiment, the heavy chain constant region sequence is SEQ ID NO: 418. In one embodiment, the light chain constant region sequence is SEQ ID NO: 448. In one embodiment, the antibody comprises a heavy chain comprising a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 167 and a heavy chain constant region amino acid sequence of SEQ ID NO: 418. In one embodiment, the antibody comprises a light chain comprising a light chain variable region (VL) amino acid sequence of SEQ ID NO: 170 and a light chain constant region amino acid sequence of SEQ ID NO: 448. In one embodiment, the antibody is antibody 1416. Antibody 1416 has a heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 167, a heavy chain constant region amino acid sequence of SEQ ID NO: 418, a light chain variable region (VL) amino acid sequence of SEQ ID NO: 170, and a light chain constant region amino acid sequence of SEQ ID NO: 448.

[0536] 5.5 Antibody Function - Binding Measurements Antibodies that specifically bind to the surface of Acinetobacter baumannii bacteria can be identified, for example, by immunoassays (e.g., ELISA), BIAcore™, or other techniques known to those of skill in the art.

[0537] An antibody specifically binds to a target if it binds with higher affinity than to any cross-reactive antigen, as determined using experimental techniques such as radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). Typically, a specific or selective response is at least twice the background signal or noise, and more typically more than 10 times the background (e.g., more than 15 times, more than 20 times, more than 50 times, or more than 100 times). For a discussion of antibody specificity, see, e.g., Paul, ed., 1989, Fundamental Immunology Second Edition, Raven Press, New York at pages 332-336.

[0538] Any suitable method can be used to determine whether an antibody binds to the surface of Acinetobacter baumannii bacteria. Such methods may include ELISA to determine antibody specificity. An antibody can be said to bind to an antigen if the level of binding to that antigen is at least 2.5-fold greater, e.g., at least 10-fold greater, than binding to a control antigen. Binding between an antibody and its cognate antigen is often referred to as specific binding. Precise identification of the residues bound by an antibody can usually be obtained using X-ray crystallography. This technique can be used to determine that the antibodies described herein bind to one or more residues of the Oxa-23 enzyme, OC1 LOS, or KL49 on the surface of Acinetobacter baumannii bacteria.

[0539] The binding assay can be conveniently measured using an indirect whole bacterial cell ELISA. Alternatively, the binding assay can be conveniently measured using OMVs rather than bacterial cells. Thus, for example, when using an ELISA assay to examine binding to live bacteria, binding to OMVs can be suitably used as plate-coating antigens.

[0540] If the antibody epitope is a linear continuous epitope, binding and binding affinity can be determined using synthetic purified peptide sequences.

[0541] The specific binding antigen of an antibody (e.g., Oxa-23, OC1 LOS, or KL49) can be determined using a phage expression library, for example, as described in Example 5. For example, shotgun A. baumannii genomic DNA is incorporated into a phage expression library. The antibody is then screened for reactivity with phage plaques from the expression library to identify individual phages that bind to the antibody. The identified phages are sequenced, and the sequencing information is used to elucidate the binding antigen of the antibody. Suitable phage methods for antigen identification are known to those of skill in the art. For example, a suitable phage method is described in Lodes MJ, Dillon DC, Houghton RL, Skeiky YA. Expression cloning. Methods Mol Med. 2004;94:91-106. doi:10.1385 / 1-59259-679-7:91. PMID:14959824 (the contents of which are incorporated herein by reference).

[0542] Identification of Oxa-23, OC1 LOS or KL49 as the binding antigen can also be performed using Western blotting on specific GC2 strains genetically identified as producing the respective molecules.

[0543] To assess binding affinity and cross-reactivity, mAbs can be screened for binding to a panel of clinically relevant CRAB isolates using high-content imaging (HCI) assays and a system for image-based morphological profiling. (Maes M, Dyson ZA, Smith SE, Goulding DA, Ludden C, Baker S, Kellam P, Reece ST, Dougan G, Bartholdson Scott JA. A novel therapeutic antibody screening method using bacterial high-content imaging reveals functional antibody binding phenotypes of Escherichia coli ST131. Sci Rep. 2020 Jul 24;10(1):12414. doi:10.1038 / s41598-020-69300-8, the contents of which are incorporated herein by reference.)

[0544] SPR can be used to determine antibody binding to Oxa-23, OC1 LOS or KL49 from a cell wall context. A suitable SPR protocol is shown below: 1. Mouse anti-human (or other relevant species-matched human, rat, or non-human vertebrate antibody constant region) IgG is coupled to a biosensor chip (e.g., a dextran-coated gold chip) such as by primary amine coupling. Thus, anti-Fc antibodies can be covalently immobilized to the chip surface by amine coupling. 2. Expose mouse anti-human IgG (or other compatible species antibody) to the test antibody (e.g., in human IgG format) to capture the test antibody on the chip; 3. Pass the test antigen over the chip capture surface at a series of concentrations up to 100 nM, for example, 0.39 nM, 1.56 nM, 6.25 nM, 25 nM, and 100 nM, as well as a control experiment of 0 nM (i.e., buffer alone). The buffer can optionally be an aqueous solution of 0.01 M HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), 0.15 M NaCl, and 0.05% v / v surfactant P20, buffered to pH 7.4; and 4. Surface plasmon resonance is used to determine the binding affinity of the test antibody to the test antigen. KD, Ka and Kd can then be calculated.

[0545] SPR can be performed using any standard SPR instrument, such as with a Biacore™, or using a ProteOn XPR36™ (Bio-Rad®).

[0546] Regeneration of the capture surface can be achieved using a 3M magnesium chloride solution, which removes the captured test antibody and allows the surface to be used for another interaction. Binding data can be fitted to a unique 1:1 model using standard techniques, e.g., analytical software such as Biacore Universal Analysis Software.

[0547] Methods for determining binding (e.g., ELISA) can also be used to determine competition between molecules, such as between a test antibody and a known antibody, and can be performed using the test antibody and the known antibody in IgG format, or optionally in scFv format.

[0548] Methods that determine binding (e.g., ELISA) can also be used to determine the cross-reactivity of antibodies with different clones or strains of Acinetobacter baumannii.

[0549] 5.6 Antibody Function - Induction of Complement Activation The complement cascade is a potent, serum-based mechanism that results in the insertion of protein pores into the membranes of Gram-negative bacteria, killing the bacteria. This protein pathway is triggered by antibodies, and therefore the ability of antibodies to trigger the complement cascade is an important functional outcome for certain antibodies of the invention.

[0550] C3b is cleaved from serum C3 protein to initiate the complement cascade, and mAb binding to bacterial membranes initiates the formation of an enzyme complex containing the complement proteins C1q, C2, and C4, which cleaves C3. Thus, detection of C3b on bacterial membranes correlates with successful initiation of the complement cascade.

[0551] The ability of an antibody to induce complement activation can be determined by an in vitro assay, such as a flow cytometry-based assay to detect mAb-induced deposition of complement component C3b on the surface of OMVs. Such an assay is described in Fisher et al., Journal of Immunological Methods, https: / / doi.org / 10.1016 / j.jim.2019.07.002, the contents of which are incorporated herein by reference. Such an assay is used in the Examples herein and involves five major steps: 1. FM4-64 stained GC2 A. baumannii OMVs are incubated with compensation beads to which the OMVs nonspecifically associate for 10 minutes, after which the bead-OMV complexes are washed and blocked with PBS 0.1% (w / v) BSA. 2. The bead-OMV complex is added to small scale expressed mAb in HEK 293 supernatant, normalized to 100 μg / ml, and incubated together for 3 hours at 37°C. 3. Complement proteins are prepared by reconstituting lyophilized guinea pig complement in gelatin veronal buffer and added to the bead-OMV-antibody complexes, followed by incubation at 37°C for 15 minutes. 4. After washing, FITC-conjugated anti-C3 detection antibody is added to the bead-based complex and incubated for an additional 15 minutes. 5. After further washing, fluorescence is assessed on an Attune NxT flow cytometer equipped with a high-throughput autosampler to identify and quantify FM4-64+FITC+bead-based immune complexes.

[0552] C3b complement deposition is reported as the fold change in geometric mean fluorescence intensity on the FITC channel / HuIgG1 isotype control.

[0553] 5.7 Gene Segments In some embodiments, the antibodies comprise VH and / or VL domains and framework regions of human germline gene segment sequences. The gene segment sequences from which exemplary antibodies described herein are derived are shown in Table 3.

[0554] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment.

[0555] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment.

[0556] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the V gene segment is IGHV3-23*04, IGHV3-9*01, IGHV2-5*10, IGHV3-9*01, or IGHV3-30*18; and / or the J gene segment is IGHJ2*01, IGHJ3*02, IGHJ4*02, IGHJ6*02, or IGHJ5*02.

[0557] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the V gene segment is IGHV3-23*04.

[0558] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the V gene segment is IGHV3-9*01.

[0559] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the V gene segment is IGHV2-5*10.

[0560] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the V gene segment is IGHV3-9*01.

[0561] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the V gene segment is IGHV3-30*18.

[0562] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the J gene segment is IGHJ2*01.

[0563] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the J gene segment is IGHJ3*02.

[0564] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the J gene segment is IGHJ4*02.

[0565] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the J gene segment is IGHJ6*02.

[0566] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the J gene segment is IGHJ5*02.

[0567] In one example, the antibody comprises an antibody VH domain derived from the recombination of a human heavy chain V gene segment, a human heavy chain D gene segment, and a human heavy chain J gene segment, wherein the heavy chain V gene segment and J gene segment are in the combination shown in Table 3 for any one of the antibodies.

[0568] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV3-15*01, IGKV3D-15*d01, IGKV1-17*01, IGKV1-9*d01, IGKV1D-39*01, IGKV1-16*02, IGKV1-6*01, IGKV3D-15*d01, IGKV1-12*01, or IGKV1D-16*01; and / or the J gene segment is IGKJ4*01, IGKJ3*01, IGKJ1*01, or IGKJ2*04.

[0569] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV3-15*01.

[0570] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV3D-15*d01.

[0571] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV1-17*01.

[0572] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV1-9*d01.

[0573] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV1D-39*01.

[0574] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV1-16*02.

[0575] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV1-6*01.

[0576] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV3D-15*d01.

[0577] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the V gene segment is IGKV1-12*01.

[0578] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the J gene segment is IGKJ4*01.

[0579] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the J gene segment is IGKJ3*01.

[0580] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the J gene segment is IGKJ1*01.

[0581] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the J gene segment is IGKJ2*04.

[0582] In one example, the antibody comprises an antibody VL domain derived from the recombination of a human light chain V gene segment and a human light chain J gene segment, wherein the light chain V gene segment and J gene segment are in the combination shown in Table 3 for any one of the antibodies.

[0583] 5.8 Sequence Identity In some examples, the antibody comprises an amino acid sequence that has a high level of sequence identity to the amino acid sequence of one of the exemplary antibodies described herein and shown in Table 1.

[0584] In one example, the amino acid sequence is at least 70% identical to the designated SEQ ID NO. In one example, the amino acid sequence is at least 75% identical to the designated SEQ ID NO. In one example, the amino acid sequence is at least 95% identical to the designated SEQ ID NO. In one example, the amino acid sequence is at least 96% identical to the designated SEQ ID NO. In one example, the amino acid sequence is at least 97% identical to the designated SEQ ID NO. In one example, the amino acid sequence is at least 98% identical to the designated SEQ ID NO. In one example, the amino acid sequence is at least 99% identical to the designated SEQ ID NO. In one example, the amino acid sequence is at least 99.5% identical to the designated SEQ ID NO.

[0585] In one example, an antibody is provided having an entire heavy chain sequence that is at least 70% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire heavy chain sequence that is at least 75% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire heavy chain sequence that is at least 80% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire heavy chain sequence that is at least 85% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire heavy chain sequence that is at least 90% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire heavy chain sequence that is at least 95% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire heavy chain sequence that is at least 96% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire heavy chain sequence that is at least 97% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire heavy chain sequence that is at least 98% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, e.g., the combination of the SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein.In one example, an antibody is provided having an entire heavy chain sequence that is at least 99% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, e.g., the combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire heavy chain sequence that is at least 99.5% identical to the amino acid sequence of the entire heavy chain sequence of any antibody disclosed herein, e.g., the combination of SEQ ID NOs for the heavy chain variable domain and heavy chain constant domain sequences disclosed herein.

[0586] In one example, an antibody is provided having an entire light chain sequence that is at least 70% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire light chain sequence that is at least 75% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire light chain sequence that is at least 80% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire light chain sequence that is at least 85% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire light chain sequence that is at least 90% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire light chain sequence that is at least 95% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire light chain sequence that is at least 96% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire light chain sequence that is at least 97% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, for example, a combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire light chain sequence that is at least 98% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, e.g., the combination of the SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein.In one example, an antibody is provided having an entire light chain sequence that is at least 99% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, e.g., the combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein. In one example, an antibody is provided having an entire light chain sequence that is at least 99.5% identical to the amino acid sequence of the entire light chain sequence of any antibody disclosed herein, e.g., the combination of SEQ ID NOs for the light chain variable domain and light chain constant domain sequences disclosed herein.

[0587] In one example, an antibody is provided that has at least 70% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 75% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 80% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 85% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 90% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 95% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 96% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 97% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 98% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 99% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein. In one example, an antibody is provided that has at least 99.5% sequence identity across both the entire heavy chain and light chain sequences with the sequence of any antibody disclosed herein.

[0588] 5.9 Substitution In some examples, the antibodies contain amino acid substitutions compared to the sequences defined herein.

[0589] In some examples, antibodies are provided that are defined by the same sequence as one of the exemplary antibodies described herein and set forth in Table 1, but the sequence includes amino acid substitutions.

[0590] Amino acid substitutions include modifications in which an amino acid is replaced with a different naturally occurring amino acid residue. Such substitutions can be classified as "conservative," in which an amino acid residue present in a polypeptide is replaced with another naturally occurring amino acid having similar properties with respect to polarity, side chain functionality, or size. Such conservative substitutions are well known in the art. Substitutions encompassed by the present invention can also be "non-conservative," in which an amino acid residue present in the peptide is replaced with an amino acid having different properties, for example, a naturally occurring amino acid from a different group (e.g., replacing a charged or hydrophobic amino acid with alanine), or a naturally occurring amino acid is replaced with a non-conventional amino acid.

[0591] In one embodiment, conservative amino acid substitutions are as described herein. For example, substitutions can be Y for F, T for S or K, P for A, E for D or Q, N for D or G, R for K, G for N or A, T for S or K, D for N or E, I for L or V, F for Y, S for T or A, R for K, G for N or A, K for R, A for S, K or P. In another embodiment, conservative amino acid substitutions can be Y for F, T for A or S, I for L or V, W for Y, M for L, N for D, G for A, T for A or S, D for N, I for L or V, F for Y or L, S for A or T, and A for S, G, T or V.

[0592] In one example, the amino acid substitutions are located outside of the CDR sequences.

[0593] 5.10 Light Chain In some examples, the antibody comprises a kappa light chain. The kappa light chain constant region amino acid and nucleotide sequences are set forth in SEQ ID NOs: 447-456.

[0594] In one example, the light chain can be a lambda light chain. The lambda light chain constant region amino acid and nucleotide sequences can be found in SEQ ID NOs: 457-481.

[0595] 5.11 Isotypes, Constant Regions and Modifications Selection of the appropriate format of the antibody (e.g., IgG4 or IgG1) can be used to achieve the desired result.

[0596] The antibody format may be an antibody with limited Fc effector function, for example an IgG4, for example a stabilized IgG4 isotype.

[0597] The antibodies described herein can comprise a human constant region, e.g., an effector-null human constant region, such as an IgG4 constant region or an IgG1 constant region, optionally wherein the constant region is IgG4-PE (SEQ ID NOs: 441-446 and 482-483), or a disabled IgG1 as defined in SEQ ID NOs: 425-426.

[0598] In a preferred embodiment, the constant region of the antibody is SEQ ID NO:418.

[0599] In other embodiments, the antibody is of any of the isotypes or constant regions defined above. In one embodiment, the constant region is wild-type human IgG1 (SEQ ID NOs: 417-424). For example, the constant region is an effector-capable IgG1 constant region, optionally with ADCC and / or CDC activity. In one embodiment, the constant region has been engineered to enhance ADCC and / or CDC and / or ADCP. In another embodiment, the constant region has been engineered to enhance effector function.

[0600] In some embodiments, antibodies may contain modifications that enhance the antibody's clustering ability, making it a better substrate for complement fixation. The Fc domain of IgG1 may be mutated, for example, at E345 or E430, to strengthen the Fc:Fc interaction between antibodies and stimulate hexamer formation, which enhances the induction of CDC and ADCC of target cells (de Jong et al., PloS Biol 14(1)e1002344 2016). Hexamer formation is optionally combined with bispecific antibody formats.

[0601] The IgG4 constant region can be any of the IgG4 constant region amino acid sequences or can be encoded by any of the nucleic acid sequences (SEQ ID NOs: 435 to 440). The heavy chain constant region can be an IgG4 containing both the Leu235Glu mutation and the Ser228Pro mutation. This "IgG4-PE" heavy chain constant region (SEQ ID NOs: 441 to 446 and 482 to 483) is effector null.

[0602] An alternative effector-null human constant region is a disabled IgG1, which is an IgG1*01 allele containing a L235A and / or a G237A mutation (e.g., LAGA, SEQ ID NOs: 425-426). In one example, an antibody or antibody fragment disclosed herein comprises an IgG1 heavy chain constant region, the sequence containing an alanine at positions 235 and / or 237 (EU index numbering). The antibody-dependent cellular phagocytosis (ADCP) mechanism is discussed in Guel et al., "Antibody-Dependent Phagocytosis of Tumor Cells by Macrophages: A Potent Effector Mechanism of Monoclonal Antibody Therapy of Cancer", Cancer Res., 75(23), December 1, 2015.

[0603] The potency of Fc-mediated effects can be enhanced by engineering the Fc domain through a variety of established techniques. Such methods increase affinity for specific Fc receptors or decrease affinity for inhibitory Fc receptors, thereby creating a potentially diverse profile of enhanced activation. This can be achieved by modifying one or several amino acid residues (e.g., as described in Lazar et al., 2006, Proc. Natl. Acad. Sci. USA, Mar. 14;103(11):4005-10, the modifications disclosed therein being incorporated herein by reference). Human IgG1 constant regions containing specific mutations or altered glycosylation at residue Asn297 (e.g., N297Q, EU index numbering) have been shown to enhance binding to specific Fc receptors. In one example, such mutations are at one or more residues selected from residues 239, 332, and 330 of the human IgG1 constant region (or equivalent positions in other IgG isotypes). In one example, the antibody or fragment comprises a human IgG1 constant region with one or more mutations independently selected from N297Q, S239D, I332E, and A330L (EU index numbering).

[0604] In another example, increased affinity for Fc receptors is achieved by modifying the native glycosylation profile of the Fc domain, for example, by generating fucosylated or defucosylated variants (as described in Natsume et al., 2009, Drug Des. Devel. Ther., 3:7-16 or Zhou Q., Biotechnol. Bioeng., 2008, Feb. 15, 99(3):652-65, the modifications described therein being incorporated herein by reference). Nonfucosylated antibodies have the tri-mannosyl core structure of the complex N-glycans of Fc that do not contain fucose residues. These glycoengineered antibodies, lacking the core fucose residue from the Fc N-glycan, may exhibit stronger ADCC than their fucosylated counterparts due to enhanced FcγRIIIa binding ability. For example, to increase ADCC, residues in the hinge region can be modified to increase binding to Fc-γRIII (see, e.g., Shields et al., 2001, J. Biol. Chem., Mar 2;276(9):6591-604, the modifications described therein are incorporated herein by reference). Thus, in one example, the antibody or fragment comprises a human IgG heavy chain constant region that is a variant of a wild-type human IgG heavy chain constant region, where the variant human IgG heavy chain constant region binds to a human Fcγ receptor selected from the group consisting of FcyRIIB and FcyRIIA with higher affinity than the wild-type human IgG heavy chain constant region binds to the human Fcγ receptor. In one example, the antibody or fragment comprises a human IgG heavy chain constant region that is a variant of a wild-type human IgG heavy chain constant region, where the variant human IgG heavy chain constant region binds to the human IgG heavy chain constant region with higher affinity than the wild-type human IgG heavy chain constant region binds to human FcyRIIB. In one example, the variant human IgG heavy chain constant region is a variant human IgG1, a variant human IgG2, or a variant human IgG4 heavy chain constant region. In one example, the variant human IgG heavy chain constant region comprises one or more amino acid mutations selected from G236D, P238D, S239D, S267E, L328F, and L328E (EU index numbering system).In another example, the variant human IgG heavy chain constant region comprises a set of amino acid mutations selected from the group consisting of: S267E and L328E; P238D and L328E; P238D and one or more substitutions selected from the group consisting of E233D, G237D, H268D, P271G, and A330R; P238D, E233D, G237D, H268D, P271G, and A330R; G236D and S267E; S239D and S267E; V262E, S267E, and L328F; and V264E, S267E, and L328F (EU index numbering system). In another example, the variant human IgG heavy chain constant region further comprises one or more amino acid mutations that reduce the affinity of the IgG for human FcγRIIIA, human FcγRIIA, or human FcγRI. In one example, FcγRIIB is expressed on a cell selected from the group consisting of a macrophage, a monocyte, a B cell, a dendritic cell, an endothelial cell, and an activated T cell. In one embodiment, the variant human IgG heavy chain constant region comprises one or more of the following amino acid mutations: G236A, S239D, F243L, T256A, K290A, R292P, S298A, Y300L, V305I, A330L, I332E, E333A, K334A, A339T, and P396L (EU index numbering system). In one example, the variant human IgG heavy chain constant region comprises a set of amino acid mutations selected from the group consisting of: S239D; T256A; K290A; S298A; I332E; E333A; K334A; A339T; S239D and I332E; S239D, A330L and I332E; S298A, E333A and K334A; G236A, S239D and I332E; and F243L, R292P, Y300L, V305I and P396L (EU index numbering system). In one example, the variant human IgG heavy chain constant region comprises a S239D, A330L or I332E amino acid mutation (EU index numbering system). In one example, the variant human IgG heavy chain constant region comprises S239D and I332E amino acid mutations (EU index numbering system). In one example, the variant human IgG heavy chain constant region is a variant human IgG1 heavy chain constant region comprising S239D and I332E amino acid mutations (EU index numbering system).In one example, the antibody or fragment thereof comprises an afucosylated Fc region. In another example, the antibody or fragment thereof is defucosylated. In another example, the antibody or fragment thereof is fucosylated.

[0605] In another example, the antibodies and fragments disclosed herein may contain a triple mutation (M252Y / S254T / T256E) that enhances binding to FcRn. For mutations in Table 2 that affect FcRn binding, see Dall'Aqua et al., Immunol 2002;169:5171-5180 (the modifications described therein are incorporated herein by reference).

[0606] Similarly, enhanced CDC can be achieved by amino acid changes that increase affinity for C1q, the first component of the classical complement activation cascade (see Idusogie et al., J. Immunol., 2001, 166:2571-2575, the modifications described being incorporated herein by reference). Another approach is to create a chimeric Fc domain made from human IgG1 and human IgG3 segments, taking advantage of the fact that IgG3 has a higher affinity for C1q (Natsume et al., 2008, Cancer Res., 68:3863-3872, these modifications are incorporated herein by reference). In another example, an antibody or antibody fragment disclosed herein may contain mutant amino acids at residues 329, 331, and / or 322 to alter C1q binding and / or reduce or eliminate CDC activity. In another example, an antibody or antibody fragment disclosed herein may contain an Fc region with modifications at residues 231 and 239, whereby amino acids are replaced to alter the antibody's ability to fix complement. In one example, the antibody or fragment has a constant region that contains one or more mutations selected from E345K, E430G, R344D, and D356R, particularly a double mutation comprising R344D and D356R (EU index numbering system).

[0607] An antibody may have a heavy chain constant region that binds to one or more types of Fc receptor but does not induce cellular effector function, i.e., does not mediate ADCC, CDC, or ADCP activity. Such a constant region may not be able to bind to a specific Fc receptor involved in inducing ADCC, CDC, or ADCP activity. An antibody may have a heavy chain constant region that does not bind to an Fcγ receptor. Thus, in one example, the constant region may contain a Leu235Glu mutation (EU index numbering system).

[0608] In another example, the antibodies disclosed herein are modified to increase or decrease serum half-life. In one embodiment, one or more of the following mutations are introduced to increase the biological half-life of the antibody: T252L, T254S, or T256F. Biological half-life can also be increased by modifying the heavy chain constant region CH1 domain or CL region to contain salvage receptor binding epitopes taken from two loops of the CH2 domain of the Fc region of IgG, as described in U.S. Pat. Nos. 5,869,046 and 6,121,022 (the modifications described in these documents are incorporated herein by reference). In another example, the Fc hinge region of an antibody or antigen-binding fragment of the invention is mutated to decrease the biological half-life of the antibody or fragment. One or more amino acid mutations are introduced into the CH2-CH3 domain interface region of the Fc-hinge fragment such that the binding of the antibody or fragment to Staphylococcus aureus protein A (SpA) is reduced compared to the SpA binding of the native Fc-hinge domain. Other methods for increasing serum half-life are known to those skilled in the art. Thus, in one example, the antibody or fragment is PEGylated. In another example, the antibody or fragment is fused to an albumin-binding domain, such as an albumin-binding single-domain antibody (dAb). In another example, the antibody or fragment is PASylated (i.e., genetically fused to a polypeptide sequence composed of PAS (XL-Protein GmbH), which forms an uncharged random coil structure with a large hydrodynamic volume). In another example, the antibody or fragment is XTENylated® / rPEGylated (i.e., genetically fused to a therapeutic peptide with a non-exactly repetitive peptide sequence (Amunix, Versartis)). In another example, the antibody or fragment is ELPylated (i.e., genetically fused to an ELP repeat sequence (PhaseBio)). These various half-life extending fusions are described in detail in Trohl, BioDrugs (2015) 29:215-239, which fusions are incorporated herein by reference.

[0609] The antibody may have a modified constant region that increases stability. Thus, in one example, the heavy chain constant region contains a Ser228Pro mutation. In another example, the antibodies and fragments disclosed herein contain a heavy chain hinge region that has been modified to alter the number of cysteine ​​residues. This modification can be used to facilitate assembly of the light and heavy chains or to increase or decrease the stability of the antibody.

[0610] 5.12 Acinetobacter baumannii Classification Clone G2 and Strain G2 GC2 strains are defined based on whole genome sequencing data and phylogenetic analysis. GC2 representative strains are available from ATCC and NCTC. All assays for OC1 LOS and Oxa-23 described herein can be reproduced using the publicly available strain NCTC 13424.

[0611] (http: / / www.pheculturecollections.org.uk / products / bacteria / detail.jsp?refId=NCTC+13424&collection=nctc, the contents of which are incorporated herein by reference)

[0612] The prototype strain LAC-4 (GenBank reference: GCA_000786735.1) is also frequently cited in the literature and can be used to reproduce all assays for KL49 described herein (https: / / www.genome.jp / kegg-bin / show_organism?org=abal.PMID:25728466.Sci Rep 5:8643(2015)DOI:10.1038 / srep08643, the contents of which are incorporated herein by reference).

[0613] Antibodies that specifically bind to the G2 clone of Acinetobacter baumannii may be cross-reactive with related antigens, such as those of other clones of Acinetobacter baumannii.

[0614] The methods for determining binding described herein can also be used to determine the cross-reactivity of antibodies with different clones or strains of Acinetobacter baumannii.

[0615] 5.13 Antibody production In some instances, the antibody is a monoclonal antibody.Methods for producing monoclonal antibodies are known, including, for example, fusing myeloma cells with cells from animals immunized with desired antigens.In other instances, monoclonal antibodies can be produced using recombinant DNA technology.

[0616] In some examples, the antibody is a human antibody. In one example, the antibody is a fully human antibody. In one example, the antibody is a fully human monoclonal antibody.

[0617] 5.14 Nucleic Acids, Vectors, and Host Cells Nucleic acids encoding the VH domain and / or VL domain of any one of the antibodies described herein are also provided. Nucleic acids encoding the VH domain of any one of the antibodies described herein are provided. Nucleic acids encoding the VL domain of any one of the antibodies described herein are provided.

[0618] The SEQ ID NOs and nucleic acid sequences encoding the VH and VL domains of each exemplary antibody described herein are provided in Table 1.

[0619] In one example, the nucleic acid sequence is at least 70% identical to the designated SEQ ID NO. In one example, the nucleic acid sequence is at least 80% identical to the designated SEQ ID NO. In one example, the nucleic acid sequence is at least 90% identical to the designated SEQ ID NO. In one example, the nucleic acid sequence is at least 95% identical to the designated SEQ ID NO. In one example, the nucleic acid sequence is at least 96% identical to the designated SEQ ID NO. In one example, the nucleic acid sequence is at least 97% identical to the designated SEQ ID NO. In one example, the nucleic acid sequence is at least 98% identical to the designated SEQ ID NO. In one example, the nucleic acid sequence is at least 99% identical to the designated SEQ ID NO. In one example, the nucleic acid sequence is at least 99.5% identical to the designated SEQ ID NO.

[0620] In one example, the nucleic acid encodes the heavy chain of any one of the antibodies described herein. In another example, the nucleic acid encodes the light chain of any one of the antibodies described herein.

[0621] In one example, the nucleic acid is an isolated and purified nucleic acid.

[0622] Also provided is a vector containing the above nucleic acid. In one example, the vector can be a CHO cell expression vector. In one example, the vector can be a HEK293 cell expression vector.

[0623] Also provided is a host cell containing the above-mentioned nucleic acid. In some examples, the host cell is a eukaryotic cell, such as a mammalian cell, preferably a CHO cell (e.g., a CHO cell grown in suspension culture). HEK293 cells are an alternative cell line for production.

[0624] 5.15 Pharmaceutical Compositions In one example, a pharmaceutical composition is provided that includes an effective amount of an antibody described herein and a pharmaceutically acceptable excipient. The effective amount of an antibody described herein to be used therapeutically will depend, for example, on the therapeutic objectives, the route of administration, and the condition of the patient. In one example, the composition includes other excipients or stabilizers.

[0625] Pharmaceutically acceptable excipients are known and include carriers, excipients, or stabilizers that are non-toxic to cells or mammals exposed to the cells or mammals at the dosages and concentrations used. Often, physiologically acceptable excipients are aqueous pH buffered solutions. Examples of physiologically acceptable excipients include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; antioxidants including low molecular weight (less than about 10 residues) polypeptides; proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as ethylenediaminetetraacetic acid (EDTA); sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or non-ionic surfactants such as TWEEN™, polyethylene glycol (PEG), and PLURONICS™.

[0626] Antibodies can be administered intravenously, through the nose, lungs, for example, as a liquid or powder aerosol (lyophilized), or by liquid spray. The compositions can also be administered parenterally or subcutaneously. When administered systemically, the compositions must be sterile, pyrogen-free, and in a physiologically acceptable solution, with due regard to pH, isotonicity, and stability. These conditions are known to those skilled in the art.

[0627] Methods of administering a prophylactic or therapeutic agent (e.g., an antibody disclosed herein) or pharmaceutical composition include, but are not limited to, parenteral administration (e.g., intradermal, intramuscular, intraperitoneal, intravenous, and subcutaneous), epidural, and mucosal (e.g., intranasal and oral routes). In a specific example, a prophylactic or therapeutic agent (e.g., an antibody disclosed herein) or pharmaceutical composition is administered intranasally, intramuscularly, intravenously, or subcutaneously. The prophylactic or therapeutic agent or composition can be administered by any convenient route, for example, by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, intranasal mucosa, rectal mucosa, intestinal mucosa, etc.), and can be administered together with other biologically active agents. Administration can be systemic or local. Each dose may or may not be administered by the same route of administration.

[0628] Various delivery systems are known and can be used to administer prophylactic or therapeutic agents (e.g., antibodies disclosed herein), including, but not limited to, liposomes, microparticles, microcapsules, recombinant cells capable of expressing the antibody, receptor-mediated endocytosis (see, e.g., Wu and Wu, J. Biol. Chem. 262:4429-4432 (1987)), construction of nucleic acids as part of retroviruses or other vectors, etc. In addition, pulmonary administration can be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent. See, e.g., U.S. Patent Nos. 6,019,968, 5,985,320, 5,985,309, 5,934,272, 5,874,064, 5,855,913, 5,290,540, and 4,880,078; and PCT Publication Nos. WO 92 / 19244, WO 97 / 32572, WO 97 / 44013, WO 98 / 31346, and WO 99 / 66903, each of which is incorporated herein by reference in its entirety.

[0629] In certain instances, it may be desirable to administer a prophylactic or therapeutic agent or pharmaceutical composition described herein locally to the area in need of treatment. This can be achieved, for example, by local infusion, by topical administration (e.g., by intranasal spray), by injection, or by implants, which are made of porous, non-porous, or gelatinous materials, including membranes, such as sialastic membranes, or fibers. When administering antibodies, care must be taken to use materials to which the antibody does not absorb.

[0630] For drugs intended for local and / or topical administration, such as by absorption into epithelial or mucocutaneous linings, the antibody may be provided as an IgA isotype antibody. For human patients, human IgA1 or human IgA2 antibodies are preferred. Drugs formulated for inhalation and / or delivery of the antibody (or its encoding nucleic acid, e.g., in a DNA vector) to the upper and / or lower respiratory tract, e.g., formulations for delivering nebulized medications, may include IgA (e.g., human IgA1 or human IgA2) antibodies. Thus, inhalers, nebulizers, and similar devices may be provided containing drugs comprising an IgA antibody or its encoding nucleic acid, along with any buffers or other excipients suitable for stabilizing the drug and / or facilitating its delivery to the target tissue.

[0631] 5.16 Therapeutic Use The antibodies described herein can be used to treat or prevent bacterial infections caused by Acinetobacter baumannii. One aspect includes the use of the antibodies or compositions described herein as pharmaceuticals.

[0632] Thus, in one example, there is provided an antibody described herein or a composition described herein for use in a method for treating a bacterial infection caused by Acinetobacter baumannii, the method comprising administering the antibody or composition to a patient. In another example, there is provided an antibody described herein or a composition described herein for use in a method for preventing a bacterial infection caused by Acinetobacter baumannii, the method comprising administering the antibody or composition to a patient.

[0633] The patient may be any animal, including but not limited to a mammal. In one embodiment, the patient is a human. In one embodiment, the patient is an adult. In one embodiment, the patient is a human over the age of 12.

[0634] In one embodiment, the bacterial infection caused by Acinetobacter baumannii is a nosocomial bacterial infection caused by Acinetobacter baumannii.

[0635] In one embodiment, the patient has a lower respiratory tract infection, eg, pneumonia, eg, ventilator-associated pneumonia.

[0636] In one embodiment, the patient has sepsis.

[0637] In one embodiment, the patient has bacteremia.

[0638] In one example, the antibody for use or composition for use as described above alleviates one or more symptoms of a bacterial infection caused by Acinetobacter baumannii.

[0639] In one example, the progression of bacterial infection caused by Acinetobacter baumannii is inhibited.

[0640] In one example, the risk of contracting a bacterial infection caused by Acinetobacter baumannii is reduced.

[0641] In one example, the risk of transmission of bacterial infection caused by Acinetobacter baumannii to and / or from a patient is reduced.

[0642] Provided herein is the use of an antibody described herein or a composition described herein in the manufacture of a medicament for treating a bacterial infection caused by Acinetobacter baumannii. Also provided is the use of an antibody described herein or a composition described herein in the manufacture of a medicament for preventing a bacterial infection caused by Acinetobacter baumannii. Thus, in one example, one or more symptoms of a bacterial infection caused by Acinetobacter baumannii are alleviated. In another example, the progression of a bacterial infection caused by Acinetobacter baumannii is inhibited. In another example, the risk of acquiring a bacterial infection caused by Acinetobacter baumannii is reduced. In another example, the risk of transmission of a bacterial infection caused by Acinetobacter baumannii to and / or from humans is reduced.

[0643] Methods for treating a bacterial infection caused by Acinetobacter baumannii in a human are provided, comprising administering to the human a therapeutically effective amount of an antibody described herein or a composition described herein. Methods for preventing a bacterial infection caused by Acinetobacter baumannii in a human are also provided, comprising administering to the human a therapeutically effective amount of an antibody described herein or a composition described herein. In one example, one or more symptoms of a bacterial infection caused by Acinetobacter baumannii are alleviated. In one example, the progression of a bacterial infection caused by Acinetobacter baumannii is inhibited. In one example, the risk of acquiring a bacterial infection caused by Acinetobacter baumannii is reduced. In one example, the risk of transmission of bacterial infection caused by Acinetobacter baumannii to and / or from humans is reduced.

[0644] In one example, the use of an antibody or composition or method described herein further comprises administering at least one additional therapeutic agent. In one example, the first antibody and the additional therapeutic agent are administered simultaneously, separately, or sequentially. In one example, the additional therapeutic agent is an additional antibody.

[0645] In one embodiment, the additional therapeutic agent is a carbapenem. In this regard, the inventors have determined that due to the mechanism of action of anti-Oxa-23 antibodies, i.e., antibodies that inhibit the activity of the Oxa-23 carbapenemase enzyme, there is a synergistic effect between administration of a carbapenem and administration of an anti-Oxa-23 mAb described herein, thereby inhibiting associated carbapenem resistance.

[0646] In one embodiment, the additional therapeutic agent is colistin.

[0647] In one example, the antibody is administered as an antibody-drug conjugate in which the antibody is linked to a drug moiety, for example, the antibody can be linked to a drug moiety that can be a cytokine, a chemokine, or a small molecule antiviral agent.

[0648] The antibodies described herein can be used to prevent death and shorten the time to recovery and hospital discharge in patients with bacterial infections caused by Acinetobacter baumannii. The patient is generally a human patient and may be a patient diagnosed with a bacterial infection caused by Acinetobacter baumannii. Furthermore, the patient may be a patient already hospitalized for another reason.

[0649] In another example, a kit for treating a bacterial infection caused by Acinetobacter baumannii is provided, the kit including an antibody described herein and instructions for administering the antibody to a subject in need of treatment. Pharmaceutical or diagnostic packs or kits comprising one or more containers filled with one or more ingredients of the pharmaceutical compositions disclosed herein, such as one or more anti-Oxa-23 antibodies provided herein, are also provided. Pharmaceutical or diagnostic packs or kits comprising one or more containers filled with one or more ingredients of the pharmaceutical compositions disclosed herein, such as one or more anti-OC1 LOS antibodies provided herein, are also provided. Pharmaceutical or diagnostic packs or kits comprising one or more containers filled with one or more ingredients of the pharmaceutical compositions disclosed herein, such as one or more anti-KL49 antibodies provided herein, are also provided. Optionally, such containers may bear a notice in a format prescribed by a government agency regulating the manufacture, use, or sale of pharmaceuticals or biological products, the notice reflecting agency approval, e.g., approval number, of the manufacture, use, or sale for human administration.

[0650] In another example, an article of manufacture includes a composition containing an antibody described herein and a container provided with a package insert or label indicating that the composition can be used to treat a bacterial infection caused by Acinetobacter baumannii. In one example, a kit for treating and / or preventing a bacterial infection caused by Acinetobacter baumannii is provided, the kit including an antibody disclosed herein in any example or combination of examples herein (and, optionally, an additional therapeutic agent described elsewhere herein), optionally in combination with a label or instructions for use in treating and / or preventing the infection in a human, optionally, the label or instructions including a marketing authorization number (e.g., an FDA or EMA approval number), and optionally, the kit including an IV or injection device containing the antibody. In another example, the kit includes the antibody contained within a container or IV bag. In another example, the container or IV bag is a sterile container or IV bag. In another example, the antibody is formulated into a pharmaceutical composition contained within a (sterile) container or contained within a (sterile) IV bag. In a further example, the kit further comprises instructions for use.

[0651] In another example, a kit for treating a bacterial infection caused by Acinetobacter baumannii is provided, comprising an antibody described herein and instructions for administering the antibody to a subject in need of treatment. In the kit, the subject in need may be specifically defined as belonging to a particular high-risk group defined by epidemiological data, risk stratification data from human health records, risk stratification by an individual's genotype for certain genes, or the presence of specific biomarkers in a human blood or other tissue sample. When the risk stratification includes a separate pharmaceutical or diagnostic pack or kit, the combined product functions as a related diagnostic / prognostic and treatment kit.

[0652] 5.17 Prevention of infection - prophylactic use The antibodies described herein can be used prophylactically. Administration of the antibodies can prevent or reduce the risk of infection with Acinetobacter baumannii. The antibodies can be used, for example, to prevent infection in at-risk individuals in high-transmission environments, such as hospitals. The antibodies can also be administered to patients on ventilators to reduce their risk of developing ventilator-associated pneumonia.

[0653] 5.18 Diagnostics The antibodies described herein can be used to detect the presence, absence, and / or levels of Acinetobacter baumannii in a patient's biological sample. In one example, the biological sample is a tissue sample (e.g., in a pathology study or biopsy sample of tissue used for diagnosis and prognosis). In another example, the biological sample is blood, plasma, serum, urine, feces, or cerebrospinal fluid (CSF). In another example, the biological sample is from a nasal or throat swab. Liquid samples are convenient for use in many types of diagnostic assays.

[0654] The antibodies described herein can be used to identify the presence, absence, and / or levels of Acinetobacter baumannii at baseline, i.e., before treatment.

[0655] The antibodies described herein can be used to guide treatment, particularly to identify the presence, absence, and / or levels of Acinetobacter baumannii during or after treatment.

[0656] The antibodies described herein can be used to monitor patients to help assess whether a course of treatment is effective and whether treatment should be continued.

[0657] In one example, the antibodies described herein are labeled with a detectable moiety, such as a radioactive label, a fluorescent label, an enzyme label, a chemiluminescent label, or a biotinyl group. Radioisotopes or radionuclides include H, C, N, S, Y, Tc, In, I, and I. Fluorescent labels include rhodamine, lanthanide fluorophores, or FITC. Enzyme labels may include horseradish peroxidase, β-galactosidase, luciferase, and alkaline phosphatase. Additional labels include, by way of example and not limitation, enzymes such as glucose-6-phosphate dehydrogenase ("G6PDH"), alpha-D-galactosidase, glucose oxidase, glucose amylase, carbonic anhydrase, acetylcholinesterase, lysozyme, malate dehydrogenase, and peroxidase; dyes; additional fluorescent labels or fluorophores, such as fluorescein and its derivatives, fluorescent dyes, GFP (GFP stands for "green fluorescent protein"), dansyl, umbelliferone, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde, and fluorescamine; fluorescent dyes, such as lanthanide cryptates and chelates, such as europium (Perkin Elmer and Cisbio Assays); chemiluminescent labels or chemiluminescers, such as isoluminol, luminol, and dioxetanes; sensitizers; coenzymes; enzyme substrates; particles, such as latex or carbon particles; metal sols; microcrystals; liposomes; cells, etc. (which may be further labeled with dyes, catalysts, or other detectable groups); molecules, such as biotin, digoxigenin, or 5-bromodeoxyuridine; toxin moieties, such as a toxin moiety selected from the group consisting of Pseudomonas exotoxin (PE or a cytotoxic fragment or variant thereof), diphtheria toxin or a cytotoxic fragment or variant thereof, botulinum toxin A, B, C, D, E, or F, ricin or a cytotoxic fragment thereof, such as ricin A, abrin or a cytotoxic fragment thereof, saporin or a cytotoxic fragment thereof, pokeweed antiviral toxin or a cytotoxic fragment thereof, and bryodin 1 or a cytotoxic fragment thereof.

[0658] In one example, an antibody can be administered to a patient, where the antibody is conjugated to a label. The presence of the label in the patient can be measured or observed, with a relatively high amount of label indicating a high risk of infection and a relatively low amount of label indicating a relatively low risk of infection. In one example, the label is an imaging agent, an isotope tag, or a fluorescent marker such as green fluorescent protein.

[0659] For diagnostic uses, antibodies with high affinity are particularly useful, especially those with fast on-rates and slow off-rates (eg, as measured by SPR).

[0660] In some embodiments, it is desirable to include two antibodies in a diagnostic assay, preferably directed against different targets on Acinetobacter baumannii. The diagnostic assay can be a double antigen binding assay (DABA). In DABA, a first antibody is used as a capture antibody that binds to Acinetobacter baumannii in the sample (for this purpose, a high-affinity antibody with a fast on-rate and a slow off-rate is desirable, as described above), and a second antibody specific for an epitope different from that of the capture antibody is used for detection. Therefore, the second antibody can be detectably labeled by direct or indirect labeling. DABA can include providing a first antibody (optionally immobilized on a surface), contacting the surface with a sample to allow capture of the antigen (if present), then washing to remove unbound antigen and sample, then exposing the surface to a detection antibody to allow binding to the antigen (if present), washing to remove unbound detection antibody, and detecting the presence of the detection antibody. The presence of the detection antibody indicates that the sample is positive for Acinetobacter baumannii. This type of assay can be used to determine whether a patient is infected with Acinetobacter baumannii.

[0661] In one example, a kit for detecting Acinetobacter baumannii in a biological sample is provided. The kit can be used to screen for Acinetobacter baumannii infection. In one example, the kit includes an antibody according to the invention described anywhere herein and a means for determining whether the antibody binds to Acinetobacter baumannii in the sample. In one example, the antibody is specific for Acinetobacter baumannii. In one example, the antibody is labeled. In another example, the antibody is an unlabeled primary antibody, and the kit includes a means for detecting the primary antibody. In one example, the detection means includes a labeled secondary antibody that is an anti-immunoglobulin antibody. The antibody can be labeled with any suitable marker, including, for example, a fluorochrome, an enzyme, a radionuclide, and a radio-opaque material.

[0662] In one example, a kit for detecting Acinetobacter baumannii is provided, the kit including an antibody described herein. In one example, the kit can also include instructions and one or more reagents for detecting Acinetobacter baumannii.

[0663] 5.19 Discovery of antibodies The present invention is an entirely new approach to the generation and discovery of antibodies for use in the diagnosis and treatment of pathogen infections, particularly bacterial infections. This new approach involves immunizing transgenic mice, such as humanized mice, with bacteria or other pathogens to generate antibodies in an antigen-independent manner, in that there is no inherent bias toward potential target antigens on the pathogen. Furthermore, this new approach provides the opportunity to combine multiple strains of pathogens in the immunization process, allowing the inventors to discover monoclonal antibodies with cross-reactivity across multiple strains of pathogens. The inventors have further discovered that this approach is particularly suitable for bacteria that produce outer membrane vesicles (OMVs), in which case pooled and purified vesicles from multiple bacterial strains can be used to immunize humanized mice. In this regard, the inventors have found an excellent correlation between antibodies that can bind to purified vesicles produced by bacteria and those that can bind to live bacteria. Furthermore, we discovered that pooled OMVs can induce cross-reactive serum responses against additional bacterial strains, thereby generating cross-reactive mAbs within a mouse polyclonal response.

[0664] Thus, the present invention provides a sample comprising multiple different strains of a pathogen, e.g., bacteria, which sample is suitable for use in immunizing transgenic mice, such as humanized mice. In one embodiment, the sample comprises pooled membrane vesicles isolated from multiple strains of the same bacterium.

[0665] Additionally, the present invention provides a method for producing polyclonal human antibodies, comprising: a) exposing a transgenic mouse, such as a humanized mouse, to an antigenic stimulus such that the mouse produces polyclonal antibodies against the antigen; and b) isolating polyclonal antibodies from the mouse; wherein the antigen comprises multiple different strains of a pathogen, e.g., a bacterium.

[0666] Additionally, the present invention provides a method comprising preparing a sample comprising multiple different strains of a pathogen, e.g., a bacterium, suitable for use in immunizing a transgenic mouse, such as a humanized mouse, hi one embodiment, the method further comprises immunizing a mouse with the prepared sample and collecting polyclonal antibodies produced by the mouse.

[0667] In one embodiment, the method further comprises characterizing the binding of the antibody produced by the mouse.

[0668] In one embodiment, the method further comprises isolating monoclonal antibodies, such as fully human monoclonal antibodies, from the polyclonal antibodies produced by the mouse.

[0669] The invention further provides transgenic mice, such as humanized mice, that produce antibodies, which have been immunized with a sample containing multiple different strains of a pathogen, eg, a bacterium.

[0670] In one embodiment, the transgenic mouse is a transgenic mouse that produces hybrid antibodies comprising human variable regions and mouse constant regions. In one embodiment, the transgenic mouse is a humanized mouse that produces antibodies with human variable regions, e.g., fully human antibodies, such as Kymab's proprietary IntelliSelect transgenic mouse platform (e.g., "Darwin").

[0671] As an alternative to mice, rats or other non-human animals such as chickens or llamas can be used for antibody discovery by immunization, as is well known in the art. [Example]

[0672] 6. Working Example 6.1 Example 1: Antibody Generation An end-to-end process enabling the generation of mAbs against current clinical strains of Acinetobacter baumannii is shown in Figure 1. Overall, our strategy targets the most relevant strains for which mAb-based therapy is most desirable due to multidrug resistance (MDR). Transgenic mice carrying humanized immunoglobulin loci that produce antibodies with human heavy and light chain variable regions were immunized with the OMV preparation.

[0673] Figure 1a. Time-resolved core genome phylogeny of GC2 Acinetobacter baumannii isolates in the Ho Chi Minh ICU. The shaded area indicates the period during which the carbapenem antibiotic imipenem was used for empirical treatment of VAP in the ICU. Labels A–E represent the five carbapenem-resistant genomic subclades in GC2. The capsular K locus subtypes of the 10 strains tested for OMV production are also listed on the right. Marked with an asterisk (*) are four strains from which OMVs were successfully generated and used to immunize Kymab Intellisellect transgenic mice.

[0674] Figure 1b. Scanning electron microscopy image of an unfixed OMV preparation generated from the A. baumannii clinical isolates used for immunization. OMVs prepared from A. baumannii strains BAL_191, BAL_276, BAL_215, and BAL_084. Approximately 95% of the OMVs in this preparation were 25-70 nm in diameter, with larger OMVs with diameters >80 nm comprising 2% of the preparation. Additionally, amorphous structures could also be observed, comprising 3% of the preparation.

[0675] Figure 2a. Regime used for OMV immunization. Ten mice received a prime dose of approximately 1 μg of OMV on study day 0. Following this, mice were divided into two study groups. Five mice from group 1 were sacrificed on day 7, and their spleens and lymph nodes were harvested. Five mice from group 2 received an additional boost immunization on day 36 before being sacrificed on day 43. Blood was collected before the prime and boost administrations and on day 7. Reactivity of these sera to the immunizing OMVs was assessed by ELISA. B cell responses from organs harvested on day 43 can be analyzed using IntelliSelect screening technology, with organs harvested on day 7. PB = prebleed; SB = sequential bleeds; TB = terminal bleed.

[0676] Figure 2b. Polyclonal serum responses to immunization OMVs from Kymab Intellisellect transgenic mice immunized with a mixed pool of four GC2 A. baumannii OMVs, as determined by ELISA. (a) Kinetics of antigen-specific IgG1 responses to the four GC2 A. baumannii OMVs used for immunization. Total antigen-specific IgG1 responses to the four individual GC2 A. baumannii OMVs used for immunization (BAL_084, BAL_191, BAL_215, and BAL_276, bold) are comparable to responses to two additional GC2 A. baumannii OMVs (BAL_339 and BAL_377) that were not present in the immunization pool on day 43 of the study. Specific IgG1 responses were comparable in all immunized mice, and all human Ig isotypes were represented by specific antibodies present in the polyclonal sera. Antigen-specific relative endpoint titers were calculated relative to a prebleed taken before the prime immunization.

[0677] 6.2 Example 2: Antibody Screening We developed a method to select antigen-specific IgG+ B cells from the spleens of GC2 CRAB OMV-immunized mice. Using the gating strategy shown in Figure 3 and FM4-64-stained OMVs as a sorting agent, we successfully isolated 2,087 OMV-binding IgG+ B cells from the spleens of GC2 CRAB OMV-immunized mice (Figure 3). After successful antigen-specific selection, we subjected the selected single cells to IgH / L sequencing and bioinformatics analysis. This analysis revealed 951 paired heavy and light chain reads, of which 530 were found to be of the IgG subclass (Figure 4b). Furthermore, 372 paired sequences were found to exist within clusters containing >2 sequences originating from a common B cell precursor. These clusters indicate B cell IgH / L affinity maturation occurring in germinal centers formed in the spleens of immunized mice, and more significantly, suggest convergent antibody evolution between immunized mice, such that clusters containing related sequences from multiple mice evolve. Based on these findings, we selected heavy and light chain antibody pairs that met the following criteria: high-quality next-generation sequencing (NGS) data, two or more amino acid mutations across the heavy and light chains indicative of affinity maturation, an FM4-64 GC2 A. baumannii OMV mean fluorescence intensity of ≥ 7.2 (after arcsine transformation), and no overlap at the amino acid level. The four most highly mutated sequences were selected from within clusters containing multiple related sequences, while more highly mutated sequences from doublets (containing two related sequences) were selected. In addition, we also selected paired sequences that were found to be related to clones previously isolated from bone marrow plasma cells from the same immunized mice and shown to bind GC2 A. baumannii OMV by ELISA. Using these criteria, 284 paired sequences were selected for DNA synthesis and subsequent vector-mediated expression as human IgG1. An additional nine sequences were selected from pools of sorted plasma cells isolated from the bone marrow of the same GC2 A. baumannii OMV-immunized mice that clustered with sequences previously found to bind the immunizing OMV by ELISA.Of the selected clones, 252 were IgG, 28 were IgM, 2 were IgE, and 11 clones were not assigned to a sort subclass in the original selection. DNA constructs expressing individual IgH and IgL pairs as human IgG1 were transfected into human embryonic kidney 293 (HEK 293) cells for small-scale antibody expression.

[0678] Antigen-binding IgG+ B cells were sorted from the spleens of GC2 CRAB OMV-immunized mice. Figure 4. Selection was performed to include only antigen-binding enriched B cells bound to FM4-64 fluorescently labeled GC2 CRAB OMV.

[0679] Figure 4a. Sunspot plot of 951 paired VH and VL chain sequences recovered from the spleens of four Kymab Intellisellect transgenic mice immunized with GC2 CRAB OMV. Each VH and VL paired sequence is represented by a circle colored by the individual mouse from which it originated. Sequences within a lineage predicted to be derived from a common B cell precursor are connected by a black line.

[0680] Figure 4b. Table showing the number of IgH&L paired sequences, proportional mapping to high-quality sequences, and allocation to clusters of related sequences indicative of actively evolving B cell responses to immunogens.

[0681] 6.3 Example 3: Antibody Binding We used ELISA to detect the binding of mAbs expressed at small scale (100–500 μg / ml) in human HEK293 cells to the GC2 A. baumannii OMVs used for immunization. In this ELISA, OMVs are used as plate-coating antigens. Using this ELISA approach, we identified 179 mAbs that bound to the immunized OMVs at levels above a threshold determined by an isotype control: human IgG1 + 3 standard deviations. It is important to note that mAb binding to the immunized GC2 A. baumannii OMVs correlates only with binding to the intact bacterial cell wall, and the target protein may be more abundant in the OMV than in the context of the native bacterial membrane. To address this, we evaluated the ability of mAbs to bind to the unfixed whole GC2 A. baumannii bacterial strain from which the immunized OMVs were derived. The ELISA protocol was adapted to utilize unfixed whole bacterial cells as the plate-coating antigen. Using this assay, 136 mAbs bound to bacterial cells at levels above the threshold determined by the isotype control: human IgG1 + 3 standard deviation, while 179 were confirmed to bind to OMVs. To further elucidate how mAb binding to OMVs correlates with mAb binding to the intact native bacterial wall of the GC2 clinical strain from which the OMVs were derived, we compared the results of both binding assays and found a close correlation between mAb binding to the target in both contexts. Seventy-five percent of the GC2 A. baumannii-binding mAbs also bound to unfixed whole cells of the GC2 A. baumannii strain from which the OMVs were derived (Figure 5a). While 25% of the OMV-binding mAbs did not bind to native bacterial membranes, only two clones were confirmed to bind to unfixed whole bacterial cells, but not to OMVs.Our data demonstrate that the use of OMVs as selection reagents for B-cell plasmablasts is highly effective in identifying IgH / L pairs that can also bind to the intact, unanchored bacterial cell walls of the clinical strains used to generate the OMVs. Furthermore, these data demonstrate the consistency of bacterial target composition between the OMVs and the native cell wall context. We believe this also applies to other Gram-negative bacteria and Acinetobacter spp., although the level of this consistency should be determined for each bacterial species used in our process.

[0682] The complement cascade is a potent, serum-based mechanism that leads to the insertion of protein pores into the membranes of Gram-negative bacteria, killing them. This protein pathway is triggered by antibodies, and therefore, the ability of antibodies to trigger the complement cascade is an important functional outcome of target engagement in our mAb discovery approach. C3b is cleaved from serum C3 protein to drive the complement cascade, and mAb binding to bacterial membranes initiates the formation of an enzyme complex containing the complement proteins C1q, C2, and C4, which cleaves C3. Thus, detection of C3b on bacterial membranes correlates with successful initiation of the complement cascade. To assess the ability of HEK 293-expressed mAbs to induce complement activation, we established an in-house high-throughput flow cytometry-based assay to detect the deposition of the complement component C3b on the surface of OMVs. We modified a published assay to accommodate FM4-64-stained GC2 A. baumannii OMVs, substituting antigen-conjugated beads because they contain target antigens in the bacterial membrane context. We previously observed and evaluated nonspecific association of FM4-64-stained OMVs to specific flow cytometry compensation beads and were able to exploit this association for our assay. Using this assay, we identified 76 mAbs that enhanced complement activation above the assay threshold determined by an isotype control: human IgG1 + 3 standard deviations (Figure 5b). Therefore, we describe an assay that prioritized the preliminary screening of mAbs in small-scale HEK 293 supernatants. We selected the assay based on its ability to distinguish binding signals between IgG1 antibodies and the IgH / L chain pair selected as the IgG1 control. These assays enabled us to identify a large panel of mAbs for further functional characterization. This triage generated a total of 136 mAbs capable of binding to the native bacterial surface of at least one of the four clinical strains used to generate the combined OMVs in the immune panel.The next level of analysis involves expression in Chinese hamster ovary (CHO) cells and purification of selected mAbs, allowing for sufficiently pure material to perform multiple in vitro and in vivo assays. To select clones for downstream analysis and further characterization, we evaluated the data from the primary assay in conjunction with sequence data to ensure that the selected IgH / L pairs covered a wide range of diversity at the sequence level. Selecting the most diverse sequences at this point maximizes the probability of selecting mAbs with distinct functional properties and the potential to target multiple epitopes on the bacterial surface.

[0683] Based on this clustering data, we selected clones with small-scale HEK 293 expression levels >100 μg / ml for CHO cell expression, purification in larger quantities (5-10 mg), and subsequent further analysis in in vitro and in vivo assays. Figure 5 illustrates this screening and selection process.

[0684] Figure 5a. Comparison of mAb binding to GC2 A. baumannii OMVs and unfixed whole bacterial cells as measured by ELISA. mAbs identified as binders in both ELISA binding assays: mAbs that bound to both unfixed whole GC2 A. baumannii bacterial cells and OMVs at levels above the assay threshold shown in the plot are shown in green. Orange are two mAbs that bound only to unfixed whole bacterial cells. mAbs unable to bind to intact bacterial cell walls are shown in white.

[0685] Figure 5b. Selection of mAbs for CHO expression and purification based on their ability to both bind to intact bacterial cell walls and induce C3b deposition, as described above. Examples of selection for subsequent CHO expression are shown in bold.

[0686] 6.4 Example 5: Target Identification Focusing on the identified cross-reactive mAbs, we used a phage expression library incorporating shotgun A. baumannii genomic DNA from strains BAL 084 and BAL 276. Because mAbs may bind to polypeptide epitopes, we screened the mAbs for reactivity with phage plaques from the phage expression library. Using this screening mechanism, we were able to identify individual phages that bound to Abs 1348 and 1349. Phage sequencing revealed that Abs 1348 and 1349 bound to Oxa-23, a class D β-lactamase, a major group of enzymes involved in resistance to carbapenem antibiotics. The identification of mAbs that bind to Oxa-23 is highly significant for targeted diagnostic screening. First, it demonstrates that Oxa-23 can be targeted by antibodies associated with or closely related to the A. baumannii cell membrane, which was previously unknown. Second, Oxa-23 is a functional enzyme that inactivates carbapenems. Because carbapenem resistance is a major clinical problem for the treatment of nosocomial A. baumannii infections, blocking the enzymatic function of Oxa-23 with mAbs may render A. baumannii susceptible to carbapenems. Bacterial lysates separated by SDS-PAGE were also examined and subjected to Western blot analysis for reactivity to individual mAbs. A blot showing the six major linear targets observed is shown in Figure 7b. Based on the cross-reactive binding patterns observed with mAbs 1042, 1043, 1403, 1405, 1407, 1408, and 1413, as well as the binding pattern for the 10 kDa target in Figure 7b, we speculated that this target might be lipooligosaccharide (LOS) type OC1. LOS types were determined for select isolates by OCL-specific PCR. PCR confirmed that all tested clinical A. baumannii isolates were OC1, with only ATCC 17978 being OCL2. LOS were then extracted (by extensive proteinase K treatment to remove any protein) and analyzed by Western blot using mAb 1042.Using the same method as the control, E. coli NCTC 13441 LPS was extracted and probed with a mAb specific for the O25b O antigen (ASN-4). Specific binding to the 10 kD target of 1-42 was observed for the OC1 isolates A. baumannii BAL_191, BAL_339, and BAL_372, but, as expected, no binding was observed for ATCC 17978 (OCL2) or E. coli NCTC 13441 (O25b). This data indicates that the 10 kD target is an OC1 LOS. We hypothesized that mAbs that bind only to strains with the K49 capsular subtype likely bind directly to capsular antigens. Capsular antigens were extracted from selected strains harboring KL49 and subsequently analyzed by SDS-PAGE and Western blot analysis using mAb 1416. These results show that mAb 1416 was able to bind to KL49 extracted from strains BAL_186 (KL49), BAL_242 (KL49), BAL_191 (KL49), BAL_316 (KL49), CM5132 (KL49), CM4980 (KL49), and CM15768 (KL49), but not to capsular antigens extracted from 91an (KL2) or BAL_339 (KL58). The presence of the KL49 capsule is associated with high virulence and increased mortality, and A. baumannii KL49 has now emerged as the dominant clone in Southeast Asia. We were able to confirm that all mAbs that bind to A. baumannii with KL49 capsular subtypes 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, and 1416 bind to KL49 by Western blot, correlating with the strong binding pattern to KL49 isolates observed in the HCI screen.

[0687] Figure 7a. Table showing the identified targets of each mAb. Methods used include phylogenetic information gathered from HCI (see above), serological expression cloning (SEC) using genomic phage libraries, and Western blot (WB) using specific mAbs. To demonstrate therapeutic efficacy, mAbs in bold (*) were tested in an in vivo challenge model of A. baumannii.

[0688] Figure 7b. An exemplary Western blot analysis shows that the mAb binds to three different targets: a high molecular weight target (KL49 capsule - top panel), a 10 kD target (OC1 LOS - middle panel), and a 30 kD protein (Oxa-23 - bottom panel).

[0689] 7. Arrays Table 1 - CDR, VH and VL sequences: The CDRs in the table below were determined according to IMGT.

[0690] [Table 1]

[0691] [Table 2]

[0692] [Table 3]

[0693] [Table 4]

[0694] [Table 5]

[0695] [Table 6]

[0696]

Table 7

[0697]

Table 8

[0698]

Table 9

[0699]

Table 10

[0700]

Table 11

[0701]

Table 12

[0702]

Table 13

[0703]

Table 14

[0704]

Table 15

[0705] Table 16

[0706] Table 17

[0707]

Table 18

[0708] Table 19

[0709] Table 20

[0710] Table 21

[0711] Table 2-Stationary area arrangement:

[0712] Table 22

[0713] Table 23

[0714] Table 24

[0715] Table 25

[0716] Table 26

[0717] Table 27

[0718] Table 28

[0719] Table 29

[0720] Table 30

[0721] Table 31

[0722] Table 32

[0723]

Table 33

[0724] Table 34

[0725] Table 35

[0726] Table 36

[0727] [Table 37]

[0728] [Table 38]

[0729] [Table 39]

[0730] [Table 40]

[0731] Table 3 - Gene segments:

[0732] [Table 41]

[0733] 8. Sections containing antibody references In sections herein relating to antibodies defined by antibody sequences, the antibody sequences may be defined by reference to an internal antibody reference number or SEQ ID NO. Any section herein listing an internal antibody reference number shall also be considered a disclosure of the same subject matter if the sequence defined by the internal antibody reference number is replaced by the corresponding SEQ ID NO. 1. Antibodies that specifically bind to the surface of Acinetobacter baumannii bacteria. 2. The antibody of paragraph 1, wherein the antibody induces complement activation (e.g., as measured by a flow cytometry-based assay). 3. The antibody according to Item 1 or 2, which specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria. 4. The antibody according to item 1 or 2, which specifically binds to Oxa-23 on outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria. 5. The antibody of any one of items 1 to 4, wherein the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR3 is the HCDR3 of antibody 1348, 1349, 1540, 1548, or 1550. 6. The antibody of item 5, wherein the HCDR3 is the HCDR3 of antibody 1348. 7. The antibody of item 5, wherein the HCDR3 is the HCDR3 of antibody 1349. 8. The antibody of item 5, wherein the HCDR3 is the HCDR3 of antibody 1540. 9. The antibody of item 5, wherein the HCDR3 is the HCDR3 of antibody 1548. 10. The antibody of item 5, wherein the HCDR3 is the HCDR3 of antibody 1550. 11. The antibody of any one of items 1 to 4, wherein the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, and the six CDRs are those of antibody 1348, 1349, 1540, 1548, or 1550. 12. The antibody of paragraph 11, wherein the antibody has six CDRs of antibody 1348. 13. The antibody of paragraph 11, wherein the antibody has six CDRs of antibody 1349. 14. The antibody of paragraph 11, wherein the antibody has six CDRs of antibody 1540. 15. The antibody of paragraph 11, wherein the antibody has six CDRs of antibody 1548. 16. The antibody described in paragraph 11, wherein the antibody has six CDRs of antibody 1550. 17. The antibody of any one of paragraphs 1 to 4, wherein the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, respectively, of antibody 1348, 1349, 1540, 1548, or 1550, and optionally has one, two, three, four, or five amino acid changes outside the complementarity-determining regions (CDRs) in the variable heavy (VH) domain sequence, and optionally has one, two, three, four, or five amino acid changes outside the complementarity-determining regions (CDRs) in the variable light (VL) domain sequence. 18. The antibody of clause 17, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1348, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1348, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 19. The antibody of clause 17, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1349, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1349, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 20. The antibody of clause 17, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1540, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1349, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 21. The antibody of clause 17, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1548, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1349, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 22. The antibody of clause 17, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1550, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1349, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 23. The antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence have at least 90%, at least 95%, at least 98%, or at least 99% identity to the variable heavy (VH) domain sequence and the variable light (VL) domain sequence, respectively, of antibody 1348, 1349, 1540, 1548, or 1550; The antibody according to any one of Aspects 1 to 4, wherein the antibody has the CDR of antibody 1348, 1349, 1540, 1548, or 1550, respectively. 24. The antibody of clause 23, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1348, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1348, with the proviso that the antibody comprises the CDRs of antibody 1348. 25. The antibody of clause 23, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1349, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1349, with the proviso that the antibody comprises the CDRs of antibody 1349. 26. The antibody of clause 23, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1349, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1540, with the proviso that the antibody has the CDRs of antibody 1540. 27. The antibody of clause 23, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1349, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1548, with the proviso that the antibody has the CDRs of antibody 1548. 28. The antibody of clause 23, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1349, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1550, with the proviso that the antibody has the CDRs of antibody 1550. 29. The antibody of any one of clauses 1 to 4, wherein the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence comprise the variable heavy (VH) domain sequence and the variable light (VL) domain sequence of antibody 1348, 1349, 1540, 1548, or 1550, respectively. 30. The antibody of paragraph 29, wherein the antibody comprises the VH and VL domain sequences of antibody 1348. 31. The antibody of paragraph 29, wherein the antibody comprises the VH and VL domain sequences of antibody 1349. 32. The antibody of paragraph 29, wherein the antibody comprises the VH and VL domain sequences of antibody 1540. 33. The antibody of paragraph 29, wherein the antibody comprises the VH and VL domain sequences of antibody 1548. 34. The antibody of paragraph 29, wherein the antibody comprises the VH and VL domain sequences of antibody 1550. 35. An antibody that binds to the same epitope on Oxa-23 as the antibody according to any one of items 1 to 34. 36. An antibody that can compete with the antibody of any one of items 1 to 34 for binding to Oxa-23. 37. The antibody described in item 1 or 2, which specifically binds to OCL1 lipooligosaccharide (LOS) on the surface of Acinetobacter baumannii bacteria. 38. The antibody described in item 1 or 2, which specifically binds to OCL1 LOS on outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria. 39. The antibody of clause 37 or clause 38, wherein the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein HCDR3 is the HCDR3 of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413. 40. The antibody of paragraph 39, wherein the HCDR3 is the HCDR3 of antibody 1042. 41. The antibody of paragraph 39, wherein the HCDR3 is the HCDR3 of antibody 1043. 42. The antibody of paragraph 39, wherein the HCDR3 is the HCDR3 of antibody 1403. 43. The antibody of paragraph 39, wherein the HCDR3 is the HCDR3 of antibody 1405. 44. The antibody of paragraph 39, wherein the HCDR3 is the HCDR3 of antibody 1407. 45. The antibody of paragraph 39, wherein the HCDR3 is the HCDR3 of antibody 1408. 46. ​​The antibody of paragraph 39, wherein the HCDR3 is the HCDR3 of antibody 1413. 47. The antibody of clause 37 or clause 38, wherein the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, and the six CDRs are those of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413. 48. The antibody of paragraph 47, wherein the antibody has six CDRs of antibody 1042. 49. The antibody of paragraph 47, wherein the antibody has six CDRs of antibody 1043. 50. The antibody of paragraph 47, wherein the antibody has six CDRs of antibody 1403. 51. The antibody of paragraph 47, wherein the antibody has six CDRs of antibody 1405. 52. The antibody of paragraph 47, wherein the antibody has six CDRs of antibody 1407. 53. The antibody of paragraph 47, wherein the antibody has six CDRs of antibody 1408. 54. The antibody of paragraph 47, wherein the antibody has six CDRs of antibody 1413. 55. The antibody of clause 37 or clause 38, wherein the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, respectively, of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable heavy (VH) domain sequence, and optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable light (VL) domain sequence. 56. The antibody of paragraph 55, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1042, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1042, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 57. The antibody of paragraph 55, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1043, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1043, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 58. The antibody of paragraph 55, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1403, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1403, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 59. The antibody of paragraph 55, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1405, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1405, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 60. The antibody of paragraph 55, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1407, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1407, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 61. The antibody of paragraph 55, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1408, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1408, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 62. The antibody of paragraph 55, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1413, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1413, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 63. The antibody of clause 37 or clause 38, wherein the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence that are at least 90%, at least 95%, at least 98%, or at least 99% identical to the variable heavy (VH) domain sequence and variable light (VL) domain sequence, respectively, of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413, with the proviso that the antibody has the six CDRs of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413, respectively. 64. The antibody of clause 63, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1042, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1042, with the proviso that the antibody has six CDRs of antibody 1042. 65. The antibody of clause 63, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1043, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1043, with the proviso that the antibody has six CDRs of antibody 1043. 66. The antibody of clause 63, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1403, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1403, with the proviso that the antibody has six CDRs of antibody 1403. 67. The antibody of clause 63, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1405, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1405, with the proviso that the antibody has six CDRs of antibody 1405. 68. The antibody of clause 63, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1407, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1407, with the proviso that the antibody has six CDRs of antibody 1407. 69. The antibody of clause 63, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1408, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1408, with the proviso that the antibody has six CDRs of antibody 1408. 70. The antibody of clause 63, wherein the variable heavy (VH) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VH domain sequence of antibody 1413, and the variable light (VL) domain sequence comprises a sequence at least 90%, at least 95%, at least 98%, or at least 99% identical to the VL domain sequence of antibody 1413, with the proviso that the antibody has six CDRs of antibody 1413. 71. The antibody of clause 37 or clause 38, wherein the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, wherein the variable heavy (VH) domain sequence and the variable light (VL) domain sequence comprise the variable heavy (VH) and variable light (VL) domain sequences of antibody 1042, 1043, 1403, 1405, 1407, 1408, or 1413, respectively. 72. The antibody of paragraph 71, wherein the antibody comprises the VH and VL domain sequences of antibody 1042. 73. The antibody of paragraph 71, wherein the antibody comprises the VH and VL domain sequences of antibody 1043. 74. The antibody of paragraph 71, wherein the antibody comprises the VH and VL domain sequences of antibody 1403. 75. The antibody of paragraph 71, wherein the antibody comprises the VH and VL domain sequences of antibody 1405. 76. The antibody of paragraph 71, wherein the antibody comprises the VH and VL domain sequences of antibody 1407. 77. The antibody of paragraph 71, wherein the antibody comprises the VH and VL domain sequences of antibody 1408. 78. The antibody of paragraph 71, wherein the antibody comprises the VH and VL domain sequences of antibody 1413. 79. An antibody that binds to the same epitope on OCL1 LOS as the antibody of any one of items 37 to 78. 80. An antibody that can compete with the antibody of any one of items 37 to 78 for binding to OCL1 LOS. 81. The antibody described in item 1 or 2, which specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria. 82. The antibody described in item 1 or 2, which specifically binds to KL49 on outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria. 83. The antibody of clause 81 or clause 82, wherein the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein HCDR3 is the HCDR3 of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416. 84. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1345. 85. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1347. 86. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1350. 87. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1351. 88. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1363. 89. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1364. 90. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1397. 91. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1398. 92. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1400. 93. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1401. 94. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1402. 95. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1404. 96. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1409. 97. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1410. 98. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1412. 99. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1414. 100. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1415. 101. The antibody of paragraph 83, wherein the HCDR3 is the HCDR3 of antibody 1416. 102. The antibody of clause 81 or clause 82, wherein the antibody comprises a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, and the six CDRs are those of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416. 103. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1345. 104. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1347. 105. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1350. 106. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1351. 107. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1363. 108. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1364. 109. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1397. 110. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1398. 111. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1400. 112. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1401. 113. The antibody of paragraph 102, wherein the antibody has the six CDRs of antibody 1402. 114. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1404. 115. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1409. 116. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1410. 117. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1412. 118. The antibody of paragraph 102, wherein the antibody has the six CDRs of antibody 1414. 119. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1415. 120. The antibody of paragraph 102, wherein the antibody has six CDRs of antibody 1416. 121. The antibody of clause 81 or clause 82, wherein the antibody comprises a variable heavy (VH) domain sequence and a variable light (VL) domain sequence, respectively, of antibody 1345, 1347, 1350, 1351, 1363, 1364, 1397, 1398, 1400, 1401, 1402, 1404, 1409, 1410, 1412, 1414, 1415, or 1416, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable heavy (VH) domain sequence, and optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity determining regions (CDRs) in the variable light (VL) domain sequence. 122. The antibody of paragraph 121, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1345, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1345, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 123. The antibody of paragraph 121, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1347, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1347, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 124. The antibody of paragraph 121, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1350, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1350, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 125. The antibody of paragraph 121, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1351, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable light (VL) domain sequence of antibody 1351, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs). 126. The antibody of paragraph 121, wherein the antibody comprises the variable heavy (VH) domain sequence of antibody 1363, optionally with 1, 2, 3, 4, or 5 amino acid changes outside the complementarity-determining regions (CDRs), and the variable l...

Claims

1. An antibody that specifically binds to the surface of Acinetobacter baumannii bacteria.

2. The antibody of claim 1 , wherein the antibody induces complement activation (e.g., as measured by a flow cytometry-based assay).

3. 3. The antibody of claim 1, which specifically binds to Oxa-23 on the surface of Acinetobacter baumannii bacteria or specifically binds to Oxa-23 on outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria.

4. The antibody (a) a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR3 is selected from the group consisting of SEQ ID NO:24, SEQ ID NO:34, SEQ ID NO:174, and SEQ ID NO:182; or (b) a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3; (i) HCDR1 consists of SEQ ID NO: 32, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 34, LCDR1 consists of SEQ ID NO: 37, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 38; (ii) HCDR1 consists of SEQ ID NO: 22, HCDR2 consists of SEQ ID NO: 23, HCDR3 consists of SEQ ID NO: 24, LCDR1 consists of SEQ ID NO: 27, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 29; (iii) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 173, HCDR3 consists of SEQ ID NO: 174, LCDR1 consists of SEQ ID NO: 149, LCDR2 consists of SEQ ID NO: 177, and LCDR3 consists of SEQ ID NO: 178, or (iv) HCDR1 consists of SEQ ID NO: 181 and HCDR2 consists of SEQ ID NO: 173 wherein HCDR3 consists of SEQ ID NO: 182, LCDR1 consists of SEQ ID NO: 185, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 186; or (c) comprising a variable heavy (VH) domain sequence and a variable light (VL) domain sequence; (i) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 31, and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 36; (ii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 21, and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 26; (iii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 172 and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 176; or (iv) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 180, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 184, optionally with 1, 2, 3, 4 or 5 amino acid changes in the variable heavy (VH) domain sequence outside the complementarity determining regions (CDRs), and optionally with 1, 2, 3, 4 or 5 amino acid changes in the variable light (VL) domain sequence outside the complementarity determining regions (CDRs); or (d) comprising a variable heavy (VH) domain sequence and a variable light (VL) domain sequence; (i) the variable heavy (VH) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 31; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 36; wherein HCDR1 consists of SEQ ID NO: 32, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 34, LCDR1 consists of SEQ ID NO: 37, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 38; (ii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 21; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 26; wherein HCDR1 consists of SEQ ID NO: 22, HCDR2 consists of SEQ ID NO: 23, HCDR3 consists of SEQ ID NO: 24, LCDR1 consists of SEQ ID NO: 27, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 29; (iii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 172; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 176; with the proviso that HCDR1 consists of SEQ ID NO:3, HCDR2 consists of SEQ ID NO:173, HCDR3 consists of SEQ ID NO:174, LCDR1 consists of SEQ ID NO:149, LCDR2 consists of SEQ ID NO:177, and LCDR3 consists of SEQ ID NO:178; or (iv) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 180; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 184; wherein HCDR1 consists of SEQ ID NO: 181, HCDR2 consists of SEQ ID NO: 173, HCDR3 consists of SEQ ID NO: 182, LCDR1 consists of SEQ ID NO: 185, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 186; or (e) comprising a variable heavy (VH) domain sequence and a variable light (VL) domain sequence; (i) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 31, and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 36; (ii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 21, and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 26; (iii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 172 and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 176; or (iv) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 180, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 184; The antibody according to any one of claims 1 to 3.

5. (a) binds to the same epitope on Oxa-23 as an antibody of any one of claims 1 to 4; or (b) capable of competing with the antibody of any one of claims 1 to 4 for binding to Oxa-23; antibody.

6. 3. The antibody of claim 1 or 2, which specifically binds to OCL1 lipooligosaccharide (LOS) on the surface of Acinetobacter baumannii bacteria or specifically binds to OCL1 LOS on outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria.

7. The antibody (a) a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR3 is selected from the group consisting of SEQ ID NO: 189, SEQ ID NO: 196, SEQ ID NO: 90, SEQ ID NO: 105, SEQ ID NO: 112, SEQ ID NO: 119, and SEQ ID NO: 146; or (b) a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3; (i) HCDR1 consists of SEQ ID NO: 32, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 189, LCDR1 consists of SEQ ID NO: 37, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 192; (ii) HCDR1 consists of SEQ ID NO: 195, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 196, LCDR1 consists of SEQ ID NO: 37, LCDR2 consists of SEQ ID NO: 9, and LCDR3 consists of SEQ ID NO: 199; (iii) HCDR1 consists of SEQ ID NO: 22, HCDR2 consists of SEQ ID NO: 89, HCDR3 consists of SEQ ID NO: 90, LCDR1 consists of SEQ ID NO: 93, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 94; (iv) HCDR1 consists of SEQ ID NO: 104, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 105, LCDR1 consists of SEQ ID NO: 27, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 108; (v) HCDR1 consists of SEQ ID NO: 111, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 112, LCDR1 consists of SEQ ID NO: 115, 2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 116; (vi) HCDR1 consists of SEQ ID NO: 104, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 119, LCDR1 consists of SEQ ID NO: 122, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 123, or (vii) HCDR1 consists of SEQ ID NO: 145, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 146, LCDR1 consists of SEQ ID NO: 149, LCDR2 consists of SEQ ID NO: 150, and LCDR3 consists of SEQ ID NO: 151; or (c) comprising a variable heavy (VH) domain sequence and a variable light (VL) domain sequence; (i) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 188, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 191; (ii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 194 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 198; (iii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 88 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 92; (iv) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 103 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 107; (v) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 110 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 114; (vi) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 118 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 121; or (vii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 144 and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 148; optionally having 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in said variable heavy (VH) domain sequence, and optionally having 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in said variable light (VL) domain sequence; or (d) comprising a variable heavy (VH) domain sequence and a variable light (VL) domain sequence; (i) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 188; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 191; wherein HCDR1 consists of SEQ ID NO: 32, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 189, LCDR1 consists of SEQ ID NO: 37, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 192; (ii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 194; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 198; wherein HCDR1 consists of SEQ ID NO: 195, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 196, LCDR1 consists of SEQ ID NO: 37, LCDR2 consists of SEQ ID NO: 9, and LCDR3 consists of SEQ ID NO: 199; (iii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 88; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 92; wherein HCDR1 consists of SEQ ID NO: 22, HCDR2 consists of SEQ ID NO: 89, HCDR3 consists of SEQ ID NO: 90, LCDR1 consists of SEQ ID NO: 93, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 94; (iv) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 103; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 107; wherein HCDR1 consists of SEQ ID NO: 104, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 105, LCDR1 consists of SEQ ID NO: 27, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 108; (v) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 110; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 114; wherein HCDR1 consists of SEQ ID NO: 111, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 112, LCDR1 consists of SEQ ID NO: 115, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 116; (vi) the variable heavy (VH) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 118; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 121; with the proviso that HCDR1 consists of SEQ ID NO: 104, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 119, LCDR1 consists of SEQ ID NO: 122, LCDR2 consists of SEQ ID NO: 28, and LCDR3 consists of SEQ ID NO: 123; or (vii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 144; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 148; wherein HCDR1 consists of SEQ ID NO: 145, HCDR2 consists of SEQ ID NO: 33, HCDR3 consists of SEQ ID NO: 146, LCDR1 consists of SEQ ID NO: 149, LCDR2 consists of SEQ ID NO: 150, and LCDR3 consists of SEQ ID NO: 151; or (e) comprising a variable heavy (VH) domain sequence and a variable light (VL) domain sequence; (i) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 188, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 191; (ii) the variable heavy (VH) domain comprises, preferably comprises, SEQ ID NO: 194 (iii) said variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 88 and said variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 92; (iv) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 103 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 107; (v) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 110 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 114; (vi) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 118, and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 121; (vii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 144, and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 148; The antibody described in claim 6.

8. (a) binds to the same epitope on OCL1 LOS as the antibody of claim 6 or 7; or (b) capable of competing with the antibody of claim 6 or 7 for binding to OCL1 LOS; antibody.

9. 3. The antibody of claim 1 or 2, which specifically binds to KL49 on the surface of Acinetobacter baumannii bacteria or specifically binds to KL49 on outer membrane vesicles (OMVs) of Acinetobacter baumannii bacteria.

10. The antibody (a) a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR3 is selected from the group consisting of SEQ ID NO:168, SEQ ID NO:5, SEQ ID NO:14, SEQ ID NO:41, SEQ ID NO:45, SEQ ID NO:50, SEQ ID NO:55, SEQ ID NO:62, SEQ ID NO:67, SEQ ID NO:72, SEQ ID NO:77, SEQ ID NO:83, SEQ ID NO:98, SEQ ID NO:126, SEQ ID NO:132, SEQ ID NO:139, SEQ ID NO:156, and SEQ ID NO:163; or (b) a variable heavy (VH) domain sequence comprising complementarity determining regions (CDRs) HCDR1, HCDR2, and HCDR3, and a variable light (VL) domain sequence comprising complementarity determining regions LCDR1, LCDR2, and LCDR3; (i) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 168, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 10; (ii) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 4, HCDR3 consists of SEQ ID NO: 5, LCDR1 consists of SEQ ID NO: 8, LCDR2 consists of SEQ ID NO: 9, and LCDR3 consists of SEQ ID NO: 10; (iii) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 14, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 19; (iv) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 41, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 19; (v) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 45, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 10; (vi) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 50, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 19; (vii) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 55, LCDR1 consists of SEQ ID NO: 58, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (viii) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 62, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (ix) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 67, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (x) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 72, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (xi) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 77, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 80; (xii) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 83, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 86; (xiii) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 97, HCDR3 consists of SEQ ID NO: 98, LCDR1 consists of SEQ ID NO: 101, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (xiv) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 126, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 129; (xv) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 132, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 135; (xvi) HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 138, HCDR3 consists of SEQ ID NO: 139, LCDR1 consists of SEQ ID NO: 142, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 86; (xvii) HCDR1 consists of SEQ ID NO: 154, HCDR2 consists of SEQ ID NO: 155, HCDR3 consists of SEQ ID NO: 156, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 159, or (xviii) HCDR1 consists of SEQ ID NO:3, HCDR2 consists of SEQ ID NO:162, HCDR3 consists of SEQ ID NO:163, LCDR1 consists of SEQ ID NO:17, LCDR2 consists of SEQ ID NO:18, and LCDR3 consists of SEQ ID NO:135; or (c) comprising a variable heavy (VH) domain sequence and a variable light (VL) domain sequence; (i) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 167 and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 170; (ii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 2 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 7; (iii) said variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 12, and said variable light (VL) domain comprises, preferably consists of, SEQ ID NO:

16. 、 (iv) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 40 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 16; or (v) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 44 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO:

47. (vi) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 49 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 52; (vii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 54, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 57; (viii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 61 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 64; (ix) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 66 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 69; (x) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 71, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 74; (xi) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 76, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

79. (xii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 82, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

85. (xiii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 96, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

100. (xiv) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 125, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

128. (xv) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 131, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

134. (xvi) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 137, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 141; (xvii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 153 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 158; or (xviii) said variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 161, and said variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 165; optionally having 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in said variable heavy (VH) domain sequence, and optionally having 1, 2, 3, 4 or 5 amino acid changes outside the complementarity determining regions (CDRs) in said variable light (VL) domain sequence; or (d) comprising a variable heavy (VH) domain sequence and a variable light (VL) domain sequence; (i) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 167; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 170; However, HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, and HCDR 3 consists of SEQ ID NO: 168, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 10; (ii) the variable heavy (VH) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 2; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 7; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 4, HCDR3 consists of SEQ ID NO: 5, LCDR1 consists of SEQ ID NO: 8, LCDR2 consists of SEQ ID NO: 9, and LCDR3 consists of SEQ ID NO: 10; (iii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 12; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 16; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 14, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 19; (iv) the variable heavy (VH) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 40; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 16; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 41, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 19; (v) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 44; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 47; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 45, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 10; (vi) the variable heavy (VH) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 49; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 52; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 50, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 19; (vii) the variable heavy (VH) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 54; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 57; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 55, LCDR1 consists of SEQ ID NO: 58, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (viii) the variable heavy (VH) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 61; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 64; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 62, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (ix) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 66; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 69; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 67, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (x) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 71; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 74; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 72, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (xi) the variable heavy (VH) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 76; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 79; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 77, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 80; (xii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 82; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 85; However, HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 83, LCDR1 consists of SEQ ID NO: 17, and LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 86; (xiii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 96; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 100; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 97, HCDR3 consists of SEQ ID NO: 98, LCDR1 consists of SEQ ID NO: 101, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 59; (xiv) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 125; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 128; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 126, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 129; (xv) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 131; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 134; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 13, HCDR3 consists of SEQ ID NO: 132, LCDR1 consists of SEQ ID NO: 17, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 135; (xvi) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 137; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 141; wherein HCDR1 consists of SEQ ID NO: 3, HCDR2 consists of SEQ ID NO: 138, HCDR3 consists of SEQ ID NO: 139, LCDR1 consists of SEQ ID NO: 142, LCDR2 consists of SEQ ID NO: 18, and LCDR3 consists of SEQ ID NO: 86; (xvii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 153; the variable light (VL) domain comprises, preferably consists of, a sequence having at least 90%, at least 95%, at least 98% or at least 99% identity to SEQ ID NO: 158; with the proviso that HCDR1 has SEQ ID NO: 154, HCDR2 has SEQ ID NO: 155, HCDR3 has SEQ ID NO: 156, LCDR1 has SEQ ID NO: 17, LCDR2 has SEQ ID NO: 18, and LCDR3 has SEQ ID NO: 159; or (xviii) the variable heavy (VH) domain comprises, or preferably consists of, a sequence having at least 90%, at least 95%, at least 98%, or at least 99% identity to SEQ ID NO: 161; The variable light (VL) domain has at least 90% affinity to SEQ ID NO: 165, at least comprising, preferably consisting of, a sequence having 95%, at least 98% or at least 99% identity thereto, wherein HCDR1 consists of SEQ ID NO:3, HCDR2 consists of SEQ ID NO:162, HCDR3 consists of SEQ ID NO:163, LCDR1 consists of SEQ ID NO:17, LCDR2 consists of SEQ ID NO:18, and LCDR3 consists of SEQ ID NO:135; or (e) comprising a variable heavy (VH) domain sequence and a variable light (VL) domain sequence; (i) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 167 and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 170; (ii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 2 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 7; (iii) said variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 12 and said variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 16; (iv) said variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 40, and said variable light (VL) domain comprises, preferably consists of, SEQ ID NO:

16. (v) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 44, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 47; (vi) said variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 49 and said variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 52; (vii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 54, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 57; (viii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 61 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 64; (ix) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 66 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 69; (x) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 71, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO: 74; (xi) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 76, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

79. (xii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 82, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

85. (xiii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 96, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

100. (xiv) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 125, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

128. (xv) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 131 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 134; (xvi) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 137 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 141; (xvii) the variable heavy (VH) domain comprises, preferably consists of, SEQ ID NO: 153 and the variable light (VL) domain comprises, preferably consists of, SEQ ID NO: 158; or (xviii) the variable heavy (VH) domain comprises, or preferably consists of, SEQ ID NO: 161, and the variable light (VL) domain comprises, or preferably consists of, SEQ ID NO:

165. The antibody described in claim 9.

11. (a) binds to the same epitope on KL49 as the antibody of claim 9 or 10; or (b) An antibody capable of competing with the antibody of claim 9 or 10 for binding to KL49.

12. The antibody according to any one of claims 1 to 11, wherein the antibody exhibits complement-dependent cytotoxicity (CDC) activity.

13. the antibody is human IgG1 or human IgG4, and optionally (a) the antibody is a human IgG1, and optionally the antibody comprises the constant region sequence of SEQ ID NO: 418; or (b) the antibody is human IgG4, and optionally the antibody comprises the constant region sequence of SEQ ID NO: 436; The antibody according to any one of claims 1 to 12.

14. The antibody of any one of claims 1 to 12, wherein the antibody is human IgA1 (e.g., comprising the constant region sequence of SEQ ID NO: 484) or human IgA2 (e.g., comprising the constant region sequence of SEQ ID NO: 485).

15. The antibody of any one of claims 1 to 13, wherein the antibody comprises a kappa (κ) light chain constant region, preferably the constant domain sequence of SEQ ID NO:

448.

16. (a) a sequence encoding the VH domain and / or the VL domain of an antibody according to any one of claims 1 to 15; or (b) a sequence encoding the heavy and / or light chain of the antibody according to any one of claims 1 to 15 A nucleic acid sequence comprising:

17. 17. A vector comprising the nucleic acid of claim 16, optionally wherein the vector is a CHO vector.

18. 18. A host cell comprising the nucleic acid of claim 16 or the vector of claim 17.

19. 1. A pharmaceutical composition comprising: (a) (i) an isolated nucleic acid encoding the antibody of any one of claims 1 to 15, or (ii) the nucleic acid of claim 16, and a pharmaceutically acceptable excipient; or (b) a pharmaceutical composition comprising the antibody of any one of claims 1 to 15 and a pharmaceutically acceptable excipient.

20. (a) the pharmaceutical composition is formulated for intravenous, intramuscular, or subcutaneous administration; and / or (b) the pharmaceutical composition further comprises at least one additional therapeutic agent, optionally, the additional therapeutic agent being: (i) at least one, preferably one or two, additional antibodies; (ii) a carbapenem; or (iii) colistin 20. The pharmaceutical composition of claim 19, wherein

21. A kit comprising: (a) the antibody of any one of claims 1 to 15, optionally in a sealed container; or (b) The pharmaceutical composition according to claim 19 or 20. Including, Optionally, the kit further comprises a label or instructions for use to prevent and / or treat a bacterial infection caused by Acinetobacter baumannii in a human, optionally the label or instructions comprises a marketing authorization number (e.g., an FDA or EMA approval number), optionally the kit comprises an IV or injection device comprising the antibody, and further optionally the antibody is contained in a hermetically sealed container.

22. An antibody according to any one of claims 1 to 15, or a pharmaceutical composition according to claim 19 or 20, or a nucleic acid according to claim 16, for use as a medicament.

23. 21. An antibody according to any one of claims 1 to 15, or a pharmaceutical composition according to claim 19 or 20, or a nucleic acid according to claim 16, for use in a method for treating or preventing a bacterial infection caused by Acinetobacter baumannii, the method comprising administering the antibody, composition or nucleic acid to a patient, and optionally (a) the presence or absence of Oxa-23 has been determined in a sample from the patient prior to administering the antibody, composition, or nucleic acid to the patient; and / or (b) the presence or absence of OCL1 LOS has been determined in a sample from the patient prior to administering the antibody, composition, or nucleic acid to the patient; and / or (c) the presence or absence of KL49 is determined in a sample from the patient prior to administering the antibody, composition, or nucleic acid to the patient; An antibody, pharmaceutical composition or nucleic acid.

24. 21. Use of an antibody according to any one of claims 1 to 15, or a pharmaceutical composition according to claim 19 or 20, or a nucleic acid according to claim 16, in the manufacture of a medicament for use in a method for treating or preventing a bacterial infection caused by Acinetobacter baumannii in a patient.

25. (a) the bacterial infection caused by Acinetobacter baumannii is a nosocomial bacterial infection caused by Acinetobacter baumannii; or (b) the patient has a lower respiratory tract infection, e.g., pneumonia; or (c) the patient has sepsis; or (d) the patient has bacteremia. An antibody, composition or nucleic acid for use according to claim 23 or the use according to claim 24.

26. 25. The antibody, composition or nucleic acid for use according to claim 23 or the use according to claim 24, wherein the method further comprises administering at least one further therapeutic agent, optionally (a) the administration of said additional therapeutic agents is simultaneous, separate or sequential; and / or (b) the additional therapeutic agent is at least one, preferably one or two, additional antibodies; and / or (c) the at least one additional therapeutic agent is a carbapenem or colistin; An antibody, composition or nucleic acid for use according to claim 23 or the use according to claim 24.

27. Use of an antibody according to any one of claims 1 to 15 for determining the presence or absence of Acinetobacter baumannii in a sample.

28. 16. A method for determining the presence or absence of Acinetobacter baumannii in a sample, the method comprising the steps of contacting the sample with an antibody according to any one of 1 to 15; and testing for binding between the antibody and Acinetobacter baumannii in the sample, wherein detection of binding indicates the presence of Acinetobacter baumannii in the sample and wherein absence of binding indicates the absence of Acinetobacter baumannii in the sample.

29. 6. Use of an antibody according to any one of claims 1 to 5 for determining the presence or absence of Oxa-23 in a sample, optionally wherein the determination of the presence or absence of Oxa-23 in the sample is used to determine a treatment protocol for the patient.

30. 10. Use of an antibody according to any one of claims 1, 2 or 6 to 8 for determining the presence or absence of OCL1 LOS in a sample, optionally wherein the determination of the presence or absence of OCL1 LOS in the sample is used to determine a treatment protocol for the patient.

31. 12. Use of an antibody according to any one of claims 1, 2 or 9 to 11 for determining the presence or absence of KL49 in a sample, optionally wherein the determination of the presence or absence of KL49 in the sample is used to determine a treatment protocol for the patient.

32. (a) the antibody is conjugated to a detectable label; and / or (b) the sample is obtained from a human infected with or suspected of being infected with Acinetobacter baumannii, and optionally the sample is obtained from a human infected with or suspected of being infected with Acinetobacter baumannii who exhibits one or more symptoms of bacterial infection; and / or (c) the sample is a serum, plasma or whole blood sample, an oral or nasal swab, urine, stool or cerebrospinal fluid (CFS), or the sample is derived from an organ or tissue suspected of being infected with Acinetobacter baumannii; Use according to any one of claims 29 to 31.

33. 16. A diagnostic kit comprising an antibody according to any one of claims 1 to 15 and optionally one or more buffers, optionally comprising a first reagent comprising the antibody according to any one of claims 1 to 15 and a second reagent comprising a detection molecule that binds to the first reagent, and further optionally wherein the detection molecule comprises a detectable label or is an antibody bound to a detectable label.

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