Staphylococcus aureus Specific Human Recombinant Polyclonal Antibodies and Uses Thereof

SEQUENCE LISTING

In accordance with 37 C.F.R. §1.52(e)(5), the present specification makes reference to a Sequence Listing (entitled “Sequence Listing”, created on Jul. 25, 2013 as a .txt file, and is 333 kilobytes). The entire contents of the Sequence Listing are incorporated herein by reference.

FIELD OF THE INVENTION

The field of the invention is molecular biology, immunology and infectious disease. More particularly, the field is anti-Staphylococcus aureus antibodies and therapeutic human recombinant polyclonal antibodies.

BACKGROUND

Antibiotic-resistant strains of Staphylococcus aureus (S. aureus) are on the rise and are a major health concern, both in the hospital setting and, increasingly, in the community at large. Methicillin-resistant S. aureus (MRSA) is currently the leading cause of death due to infectious disease in the United States, surpassing deaths from HIV/AIDS and tuberculosis combined. The death rate from invasive MRSA infection is now 20% (Heron, M. P. et al., 2008. 56: p. 1-52). Resistant forms of S. aureus have emerged within a few years of the introduction of each new class of antibiotics (Kirby, W. M., SCIENCE (1944) 99:452-453; Boucher, H. W. et al., CLIN INFECT DIS (2009) 48:1-12). For example, in the last decade, the first cases of vancomycin-resistant S. aureus (VRSA), and vancomycin-intermediate resistant S. aureus (VISA) have been reported. Given the current status in research and development of new antibiotics, resistance in bacteria is increasing faster than our ability to develop novel antibiotics to treat resistant strains (Boucher, H. W. and G. Sakoulas, CLIN INFECT DIS (2007) 45:601-8; Walsh, C., NAT REV MICROBIOL (2003) 1:65-70). Alternative treatments are therefore needed to replace those that are increasingly ineffective.

Recent research has shown that humans infected with S. aureus have a diverse humoral immune reaction to the organism (Verkaik, N. J. et al., EUR J CLIN MICROBIOL INFECT DIS (2010) 29:509-18; Verkaik, N. J. et al., CLIN INFECT DIS (2010) 50:61-8). Likewise, studies on the S. aureus exoproteome indicate that few strains express the same spectrum of antigens, and even antigens expressed in common between strains may be expressed at widely varying levels and in dissimilar temporal expression patterns (von Eiff, C. et al., DIAGN MICROBIOL INFECT DIS (2004) 49:157-62; Bania, J. et al., INT J FOOD MICROBIOL (2006) 108: 36-41; Ziebandt, A. K. et al., PROTEOMICS (2010) 10:1634-44).

One peptide that appears to be conserved among S. aureus strains and plays a role in the hemolytic activity of S. aureus is delta-hemolysin (δ-HL; also known as delta-toxin). Recent studies have shown that the hemolytic activity of delta-toxin may be modulated by interaction with lipid raft regions of the cell membrane (Pokorny, A. and P. F. Almeida, BIOCHEMISTRY (2005) 44(27): 9538-44). In addition to delta toxin, there have been six more small cytolytic peptides identified. These peptides were identified by genome analysis (Wang, R. et al., NATURE MEDICINE (2007) 13: 1510-1514). The peptides are represented in all strains tested by Wang et al. (2007) and had higher levels of expression in community acquired (CA) MRSA strains. The expression of these peptides are theorized to be one means by which CA-MRSA strains have a greater virulence compared to hospital acquired (HA) strains. Deletion of any of the six cytolytic peptides decreases virulence of MRSA strains in various in vitro and in vivo models (Wang, R. et al., NATURE MEDICINE (2007) 13: 1510-1514).

Thus, there is a need for improved therapeutic agents that can be used to treat and/or prevent S. aureus infections.

SUMMARY

The invention is based, in part, upon the discovery of human polyclonal antibody compositions that bind one or more strains of S. aureus. In one aspect, the disclosed polyclonal antibody compositions comprise at least three different human antibodies that individually bind one or more S. aureus strains. In certain embodiments, the disclosed polyclonal antibody compositions bind to at least three different strains of S. aureus. Exemplary polyclonal antibodies described herein contain specific S. aureus binding sites based on the CDRs of individual antibodies of the polyclonal antibody composition. The individual antibodies of the polyclonal antibody composition may bind proteins that are known or likely to be involved in S. aureus virulence (e.g., delta-toxin) or, alternatively, they may bind previously uncharacterized S. aureus target proteins. The disclosed human polyclonal antibody compositions can neutralize the activity of S. aureus toxins, cell surface antigens and/or immunomodulating antigens. In an exemplary embodiment, the disclosed human polyclonal antibody compositions are broad-spectrum therapeutic antibodies with neutralizing activity against multiple S. aureus proteins that are present on one or more S. aureus strains. In certain embodiments, the disclosed recombinant polyclonal antibody compositions mimic the natural human immune response. It is contemplated herein that the disclosed recombinant polyclonal antibody compositions provide protection against a range of virulence factors. Such polyclonal antibodies can be used as therapeutic agents to treat S. aureus infections including antibiotic-resistant S. aureus strains.

Also disclosed herein are isolated, individual human antibodies, or antigen binding fragments thereof, that specifically bind one or more strains of S. aureus, including antibiotic resistant strains (e.g., MRSA). In one embodiment, an isolated human antibody as described herein binds (e.g., specifically binds) to S. aureus delta-toxin (e.g., antibody 5.6.H9 and antibody 5.55.D2). In another embodiment, an isolated human antibody described herein binds (e.g., specifically binds) to the toxin phenol soluble modulin beta-1 (e.g., antibody 22.18A.E9).

These and other aspects and advantages of the invention will become apparent upon consideration of the following figures, detailed description, and claims. As used herein, “including” means without limitation, and examples cited are non-limiting.

DESCRIPTION OF THE DRAWINGS

The invention can be more completely understood with reference to the following drawings.

FIG. 1 (prior art) is a schematic representation of a typical naturally-occurring antibody. Naturally occurring antibodies are multimeric proteins that contain four polypeptide chains. Two of the polypeptide chains are called heavy chains (H chains), and two of the polypeptide chains are called light chains (L chains). The immunoglobulin heavy and light chains are connected by an interchain disulfide bond. The immunoglobulin heavy chains are connected by interchain disulfide bonds. A light chain consists of one variable region (V_L) and one constant region (C_L). The heavy chain consists of one variable region (V_H) and at least three constant regions (CH₁, CH₂and CH₃). The variable regions determine the specificity of the antibody. Each variable region comprises three hypervariable regions also known as complementarity determining regions (CDRs) flanked by four relatively conserved framework regions (FRs). The three CDRs, referred to as CDR₁, CDR₂, and CDR₃, contribute to the antibody binding specificity.

FIG. 2 is a series of panels showing data from a representative plate (plate 5.6) of isolated fully human antibodies. FIG. 2A is a representative FACS analysis showing the population of CD38+/CD19+ plasma cells targeted for cloning; FIG. 2B shows the amplified variable heavy and light antibody genes from individual plasma cells in a 96-well plate; FIG. 2C shows representative data from an antibody expression ELISA showing that the majority of amplified antibody cognate pairs are cloned and are able to express antibody; FIGS. 2D and E show data from screening ELISA assays in which a well H9 was scored as a positive against S. aureus protein in FIG. 2D and wells H2 and A12 were scored as positives in FIG. 2E. The hits were confirmed with multiple replicates in the ELISA shown in FIG. 2F.

FIG. 3 is a graph showing that an anti-S. aureus recombinant polyclonal antibody mixture of five antibodies can protect mice from a challenge with live S. aureus (community acquired-MRSA strain, USA300) at 3.5×10⁸CFU or 5×10⁸CFU (⋄, 5 antibody composition at 3.5×10⁸CFU; □, 5 antibody composition at 5×10⁸CFU; ▴, PBS at 3.5×10⁸CFU (negative control); and x, vancomycin at 2×10⁹CFU (positive control).

FIG. 4 is a graph showing that anti-S. aureus recombinant polyclonal antibody mixtures of five antibodies at a dose of 1 mg/kg at 72 hours shift the LD₅₀curve (e.g., increase resistance to S. aureus infection) in a live S. aureus bacterial challenge (community acquired-MRSA strain, USA300) in mice (♦, PBS LD₅₀=2.75×10⁸CFU; ◯, five antibody composition LD₅₀=5.0×10⁸CFU.

FIG. 5 is a graph showing that an anti-S. aureus recombinant polyclonal antibody mixture of seven antibodies can protect mice from a challenge with live S. aureus (methicillin-sensitive S. aureus strain, Wood-46) at 2×10⁸CFU or 4×10⁸CFU (0, 7 antibody composition at 2×10⁸CFU; ▪, 7 antibody composition at 4×10⁸CFU; ◯, PBS at 2×10⁸CFU (negative control); ▴, PBS at 4×10⁸CFU (negative control); and x, vancomycin at 4×10⁸CFU (positive control).

FIG. 6 is a graph showing that anti-S. aureus recombinant polyclonal antibody mixtures of seven antibodies at a dose of 1 mg/kg at 72 hours shift the LD₅₀curve (e.g., increase resistance to S. aureus infection) in a live S. aureus bacterial challenge (methicillin-sensitive S. aureus strain, Wood-46) in mice (♦, PBS LD₅₀=1.8×10⁸CFU; −◯, seven antibody composition LD₅₀=3.75×10⁸CFU.

FIG. 7 is a graph showing that anti-S. aureus recombinant polyclonal antibody mixtures of five, 10 and 19 antibodies can protect mice from a challenge with live S. aureus (USA300) at 1×10⁹CFU (□, 5 antibody composition #2 at 1×10⁹CFU; x, 5 antibody composition #3 at 1×10⁹CFU; , 10 antibody composition at 1×10⁹CFU; 0, 19 antibody composition at 1×10⁹CFU; and ▴, PBS at 1×10⁹CFU (negative control).

FIG. 8 is a graph showing the number of anti-S. aureus antibodies that react with various strains of S. aureus.

FIG. 9 is a graph showing that anti-S. aureus recombinant polyclonal antibody mixtures with the capacity of binding to the cell surface of the Wood-46 S. aureus strain can enhance the ability of white blood cells to opsonize the bacteria.

DETAILED DESCRIPTION

The human recombinant polyclonal anti-S. aureus antibody compositions disclosed herein are based, in part, on the antigen binding sites of certain human antibodies that have been selected on the basis of binding and neutralizing activity of one or more S. aureus strains. The terms “anti-S. aureus polyclonal antibody” and “anti-S. aureus recombinant polyclonal antibody” describe a composition of recombinantly produced diverse antibody molecules, where the individual members of the polyclonal composition are capable of binding to at least one epitope on S. aureus or an S. aureus secreted protein (e.g., a toxin or immunomodulator) or a cell surface antigen and where the polyclonal composition as a whole is capable of neutralizing S. aureus. In an exemplary embodiment, an anti-S. aureus polyclonal antibody neutralizes S. aureus and/or one or more antibiotic-resistant S. aureus strains. It is contemplated that the disclosed anti-S. aureus polyclonal antibodies are essentially free from immunoglobulin molecules that do not bind to S. aureus or variant strains thereof (e.g., at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 100% of the antibodies contained in the polyclonal composition bind to one or more strains of S. aureus).

As described herein, the diversity of antibodies included in an anti-S. aureus recombinant polyclonal antibody composition provide a surprising benefit over monoclonal and biclonal (e.g., a mixture of two monoclonal antibodies) antibodies because lower dosages of the polyclonal antibody composition may be administered to prevent or treat S. aureus infection. For example, it is contemplated herein that the synergistic action of the individual component antibodies in the polyclonal composition allow the polyclonal composition to be effective at lower doses than is possible with conventional monoclonal antibody therapy. In addition, because a polyclonal antibody composition binds to multiple different proteins, the composition as a whole can use lower amounts of each individual antibody to prevent or treat S. aureus infections. Further, unlike monoclonal or biclonal antibody compositions, polyclonal antibody compositions do not present the same concerns regarding the generation of drug resistance to a single or small number of agents (e.g., development of resistant S. aureus strains due to the monovalent nature of a monoclonal antibody's mode of action). It is also contemplated herein that the use of human antibodies in the polyclonal antibody composition are less likely to evoke an immune response compared to monoclonal antibodies, even fully human monoclonal antibodies, due to the complex nature of the polyclonal composition.

In view of the neutralizing activity of the disclosed polyclonal antibodies, they are useful for modulating the growth and/or colonization of one or more S. aureus strains including antibiotic-resistant S. aureus strains in a host cell; reducing or killing one or more strains of S. aureus including antibiotic-resistant S. aureus strains; and/or treating or preventing a S. aureus infection including infection with an antibiotic-resistant strain in a mammal. An anti-S. aureus polyclonal antibody may bind to S. aureus antigens in a multivalent manner, which may result in synergistic neutralization, improved phagocytosis of infected cells by macrophages, improved antibody-dependent cellular cytotoxicity (ADCC) against infected cells, and/or increased complement activity. It is contemplated herein that S. aureus is a multifaceted pathogen that may be neutralized using a multifaceted antibody approach that targets various antigens thereby enhancing the capacity of the immune system (e.g., opsonization) to eliminate these bacteria.

In one embodiment, the diversity of the recombinant polyclonal antibody is located in the variable regions (e.g., V_Hand V_Lregions) of the individual antibodies in the polyclonal antibody composition, in particular, in the CDR₁, CDR₂, and CDR₃regions of the immunoglobulin heavy and/or light chains. For example, the individual antibodies of the polyclonal antibody composition contain (a) an immunoglobulin heavy chain variable region comprising the structure CDR_H1-CDR_H2-CDR_H3and (b) an immunoglobulin light chain variable region comprising the structure CDR_L1-CDR_L2-CDR_L3, wherein the heavy chain variable region and the light chain variable region together define a single binding site for binding to one or more S. aureus strains by binding to an antigen of S. aureus or an S. aureus antigenic epitope. An individual antibody of the polyclonal composition may also bind an S. aureus secreted protein or an antigenic epitope on the secreted protein. In some embodiments, each individual antibody of the polyclonal composition binds to an epitope, which is not bound by any other member of the polyclonal composition. In other embodiments, one or more S. aureus antigens or antigenic epitopes may be bound by more than one individual antibody of the polyclonal composition.

An individual antibody molecule of the recombinant polyclonal antibody composition may be characterized by its variable region sequences (i.e., V_Hand V_Lregion), or by its CDR₁, CDR₂, and CDR₃regions of immunoglobulin heavy and light chains. When the individual antibodies of the polyclonal composition are defined by their heavy and light chain CDR regions, it is contemplated that the CDR regions are interposed between human immunoglobulin framework regions (FRs).

It is understood that each of the antibodies discussed above can be an intact tetrameric antibody. Alternatively, the antibody can be an antigen-binding fragment of an antibody. Antibody fragments include Fab, Fab′, F(ab′)₂, and Fv fragments, and single chain antibodies (e.g., scFv).

An antibody, or antigen binding fragment thereof, may also be conjugated to an effector agent such as a small molecule toxin, a drug, or a radionuclide using standard in vitro conjugation chemistries. If the effector agent is a polypeptide, the antibody can be chemically conjugated to the effector or joined to the effector as a fusion protein. Construction of fusion proteins is within ordinary skill in the art.

Human antibodies are selected based on binding to one or more S. aureus strains. Individual antibodies of the polyclonal composition may bind a protein associated with S. aureus virulence, such as, but not limited to coagulase, leukocidin (Luk), panton-valentine leukocidin (PVL), aureolysin, staphylokinase (SAK), beta-hemolysin (β-HL), delta-hemolysin (δ-HL), gamma-hemolysin (γ-HL), alpha-toxin (α-toxin), staphylococcal complement inhibitor (SCIN), enterotoxins, and adhesions (e.g., clumping factor A (ClfA), clumping factor B (ClfB), fibronectin binding protein (FnbpA), and fibronectin binding protein B (FnbpB). Additional S. aureus target proteins for binding by a S. aureus antibody include SdrD (a cell surface protein containing serine-aspartate (SD) repeats with organization and sequence similarity to fibrinogen-binding clumping factors ClfA and ClfB), IsaA, Aux1 (a transmembrane protein phosphatase), and LP309 (a lipoprotein). The disclosed antibodies may also bind to uncharacterized S. aureus proteins.

In certain embodiments, an anti-S. aureus polyclonal antibody binds to at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least 15, at least 20, at least 25 or more S. aureus proteins. In an exemplary embodiment, an anti-S. aureus polyclonal antibody binds to at least three S. aureus proteins. In certain embodiments, the three proteins may include a cell surface antigen, a toxin and/or an immunomodulator produced by S. aureus. In one embodiment, an anti-S. aureus polyclonal antibody binds at least a cell surface antigen on one or more strains of S. aureus and a toxin produced by one or more strains of S. aureus. In another embodiment, an anti-S. aureus polyclonal antibody binds at least a cell surface antigen on one or more strains of S. aureus and an immunomodulator produced by one or more strains of S. aureus. In yet another embodiment, an anti-S. aureus polyclonal antibody binds at least a toxin produced by one or more strains of S. aureus and an immunomodulator produced by one or more strains of S. aureus. In certain embodiments, the at least 2, 3, 4, 5, 10, 15, 20, 25 or more proteins are on more than one strain of S. aureus. It is contemplated herein that the broad spectrum nature of the disclosed anti-S. aureus antibody compositions may be attributed to the inclusion of individuals antibodies that bind a protein present on more than one strain of S. aureus (e.g., conserved proteins). In addition, the broad spectrum efficacy of the disclosed polyclonal antibodies may be attributed to the inclusion of certain antibodies that bind antigens associated with only one or two S. aureus strains.

An anti-S. aureus polyclonal antibody composition may also be composed of individual antibodies raised by the immune response of a donor (e.g., a human), which has been vaccinated or infected with S. aureus. Further, if antibodies to a particular antigen are known to be relevant and/or effective in the protection, neutralization and/or elimination of S. aureus infection, such antibodies may be raised by immunization of a donor with that particular antigen.

It is contemplated herein that the disclosed recombinant polyclonal antibodies are not naturally occurring antibodies isolated from human blood. Exemplary recombinant polyclonal antibodies described herein are a mixture of antibodies, wherein each individual antibody may be expressed from a cell or cell line transfected with an expression vector comprising the coding sequence of the antibody, which is not naturally associated with the cell.

A human recombinant polyclonal anti-S. aureus antibody disclosed herein may comprise at least three, at least 4, at least 5, at least 7, at least 10, at least 15, at least 20, at least 25 or more antibodies. In exemplary embodiments, the recombinant polyclonal antibodies disclosed herein may comprise about 3 to about 30 antibodies, about 3 to about 25 antibodies, about 3 to about 20 antibodies, about 3 to about 15 antibodies, about 3 to about 10 antibodies, about 3 to about 5 antibodies, about 5 to about 30 antibodies, about 5 to about 25 antibodies, about 5 to about 20 antibodies, about 5 to about 15 antibodies, about 5 to about 10 antibodies, about 8 to about 30 antibodies, about 8 to about 25 antibodies, about 8 to about 20 antibodies, about 8 to about 15 antibodies, about 8 to about 10 antibodies, about 10 to about 30 antibodies, about 10 to about 25 antibodies, about 10 to about 20 antibodies, about 10 to about 15 antibodies, about 15 to about 25 antibodies, about 15 to about 20 antibodies, about 20 to about 25 antibodies, and about 25 to about 30 antibodies.

A polyclonal anti-S. aureus antibody may comprise immunoglobulin heavy and light chain variable regions or, heavy and light chain CDR regions, from two, three, four, five, ten or more of the following antibodies as disclosed herein: 1.62.B9, 5.11.H10, 5.6.H2, 5.6.H9, 5.17.F8, 5.19.F12, 5.23.C9, 5.23.C12, 5.27.A11, 8.51.G11, 9.51.H9, 18.43.D8, 22.22.E7, 8.51.G10, 5.24A.A7, 5.24A.F3, 5.8B.H4, 26.51.E1, 22.21.A7, 22.18A.E9, 5.52.H10, 5.15.C1, 5.54.E6, 5.55.D2, 22.14.A1, 26.53.B4, 5.63.E2, 5.64.G4, 43.52.A11, 43.52.E12 and 43.62.E2, wherein each of the disclosed antibodies comprise the immunoglobulin heavy and light chain CDR1, CDR2, CDR3 sequences set forth in Table 3. For example, antibody 5.6.H9 comprises the CDR1, CDR2, and CDR3 sequences of an immunogloblulin heavy chain amino acid sequence of SEQ ID NO: 38 and the CDR1, CDR2, and CDR3 of an immunoglobulin light chain amino acid sequence of SEQ ID NO: 40. Also, as disclosed in Table 3, for example, antibody 5.6.H9 comprises an immunoglobulin heavy chain comprising a CDR_H1comprising the amino acid sequence of SEQ ID NO: 41, a CDR_H2comprising amino acid sequence of SEQ ID NO: 42 and a CDR_H3comprising an amino acid sequence of SEQ ID NO: 43; and an immunoglobulin light chain comprising a CDR_L1comprising the amino acid sequence of SEQ ID NO: 44, a CDR_L2comprising the amino acid sequence of DAS and a CDR_L3comprising an amino acid sequence of SEQ ID NO: 45.

Exemplary recombinant polyclonal antibody compositions including two antibodies disclosed herein are shown in Table 1.

TABLE 1

5.6.H9
5.11.H10
5.27.A11
5.17.F8
18.43.D8
5.19.F12
8.51.G11
8.51.G10
22.22.E7
5.23.C9
5.23.C12

5.6.H9

X
X
X
X
X
X
X
X
X
X

5.11.H10
X

X
X
X
X
X
X
X
X
X

5.27.A11
X
X

X
X
X
X
X
X
X
X

5.17.F8
X
X
X

X
X
X
X
X
X
X

18.43.D8
X
X
X
X

X
X
X
X
X
X

5.19.F12
X
X
X
X
X

X
X
X
X
X

8.51.G11
X
X
X
X
X
X

X
X
X
X

8.51.G10
X
X
X
X
X
X
X

X
X
X

22.22.E7
X
X
X
X
X
X
X
X

X
X

5.23.C9
X
X
X
X
X
X
X
X
X

X

5.23.C12
X
X
X
X
X
X
X
X
X
X

9.51.H9
X
X
X
X
X
X
X
X
X
X
X

5.24A.F3
X
X
X
X
X
X
X
X
X
X
X

5.24A.A7
X
X
X
X
X
X
X
X
X
X
X

5.8B.H4
X
X
X
X
X
X
X
X
X
X
X

5.52.H10
X
X
X
X
X
X
X
X
X
X
X

22.18A.E9
X
X
X
X
X
X
X
X
X
X
X

22.21.A7
X
X
X
X
X
X
X
X
X
X
X

5.15.C1
X
X
X
X
X
X
X
X
X
X
X

5.54.E6
X
X
X
X
X
X
X
X
X
X
X

5.55.D2
X
X
X
X
X
X
X
X
X
X
X

26.51.E1
X
X
X
X
X
X
X
X
X
X
X

22.14.A1
X
X
X
X
X
X
X
X
X
X
X

26.53.B4
X
X
X
X
X
X
X
X
X
X
X

5.63.E2
X
X
X
X
X
X
X
X
X
X
X

5.64.G4
X
X
X
X
X
X
X
X
X
X
X

43.52.A11
X
X
X
X
X
X
X
X
X
X
X

43.52.E12
X
X
X
X
X
X
X
X
X
X
X

43.62.E2
X
X
X
X
X
X
X
X
X
X
X

9.51.H9
5.24A.F3
5.24A.A7
5.8B.H4
5.52.H10
22.18A.E9
22.21.A7
5.15.C1
5.54.E6
5.55.D2

5.6.H9
X
X
X
X
X
X
X
X
X
X

5.11.H10
X
X
X
X
X
X
X
X
X
X

5.27.A11
X
X
X
X
X
X
X
X
X
X

5.17.F8
X
X
X
X
X
X
X
X
X
X

18.43.D8
X
X
X
X
X
X
X
X
X
X

5.19.F12
X
X
X
X
X
X
X
X
X
X

8.51.G11
X
X
X
X
X
X
X
X
X
X

8.51.G10
X
X
X
X
X
X
X
X
X
X

22.22.E7
X
X
X
X
X
X
X
X
X
X

5.23.C9
X
X
X
X
X
X
X
X
X
X

5.23.C12
X
X
X
X
X
X
X
X
X
X

9.51.H9

X
X
X
X
X
X
X
X
X

5.24A.F3
X

X
X
X
X
X
X
X
X

5.24A.A7
X
X

X
X
X
X
X
X
X

5.8B.H4
X
X
X

X
X
X
X
X
X

5.52.H10
X
X
X
X

X
X
X
X
X

22.18A.E9
X
X
X
X
X

X
X
X
X

22.21.A7
X
X
X
X
X
X

X
X
X

5.15.C1
X
X
X
X
X
X
X

X
X

5.54.E6
X
X
X
X
X
X
X
X

X

5.55.D2
X
X
X
X
X
X
X
X
X

26.51.E1
X
X
X
X
X
X
X
X
X
X

22.14.A1
X
X
X
X
X
X
X
X
X
X

26.53.B4
X
X
X
X
X
X
X
X
X
X

5.63.E2
X
X
X
X
X
X
X
X
X
X

5.64.G4
X
X
X
X
X
X
X
X
X
X

43.52.A11
X
X
X
X
X
X
X
X
X
X

43.52.E12
X
X
X
X
X
X
X
X
X
X

43.62.E2
X
X
X
X
X
X
X
X
X
X

26.51.E1
22.14.A1
26.53.B4
5.63.E2
5.64.G4
43.52.A11
43.52.E12
43.62.E2

5.6.H9
X
X
X
X
X
X
X
X

5.11.H10
X
X
X
X
X
X
X
X

5.27.A11
X
X
X
X
X
X
X
X

5.17.F8
X
X
X
X
X
X
X
X

18.43.D8
X
X
X
X
X
X
X
X

5.19.F12
X
X
X
X
X
X
X
X

8.51.G11
X
X
X
X
X
X
X
X

8.51.G10
X
X
X
X
X
X
X
X

22.22.E7
X
X
X
X
X
X
X
X

5.23.C9
X
X
X
X
X
X
X
X

5.23.C12
X
X
X
X
X
X
X
X

9.51.H9
X
X
X
X
X
X
X
X

5.24A.F3
X
X
X
X
X
X
X
X

5.24A.A7
X
X
X
X
X
X
X
X

5.8B.H4
X
X
X
X
X
X
X
X

5.52.H10
X
X
X
X
X
X
X
X

22.18A.E9
X
X
X
X
X
X
X
X

22.21.A7
X
X
X
X
X
X
X
X

5.15.C1
X
X
X
X
X
X
X
X

5.54.E6
X
X
X
X
X
X
X
X

5.55.D2
X
X
X
X
X
X
X
X

26.51.E1

X
X
X
X
X
X
X

22.14.A1
X

X
X
X
X
X
X

26.53.B4
X
X

X
X
X
X
X

5.63.E2
X
X
X

X
X
X
X

5.64.G4
X
X
X
X

X
X
X

43.52.A11
X
X
X
X
X

X
X

43.52.E12
X
X
X
X
X
X

X

43.62.E2
X
X
X
X
X
X
X

Exemplary recombinant polyclonal antibody compositions including three antibodies disclosed herein include: 5.6.H9, 22.18A.E9 and 5.55.D2; 5.6.H9, 22.18A.E9 and 9.51.H9; 5.6 H9, 22.18A.E9 and 5.11.H10; 5.6 H9, 22.18A.E9 and 5.23.C12; 5.6.H9, 22.18A.E9 and 5.52.H10; 5.6.H9, 22.18A.E9 and 18.43.D8; 5.6 H9, 22.18A.E9 and 8.51 G10; 5.6.H9, 22.18A.E9 and 8.51.G11.

It is also contemplated herein that the disclosed recombinant human polyclonal antibody compositions may include one or more antibodies that compete with one of the disclosed antibodies for binding to one or more S. aureus strains, for example, under the conditions described in Example 4. Exemplary S. aureus strains for determining whether an antibody competes with binding to a disclosed antibody include ATCC Strain BAA-1717 (also known as USA300), ATCC Strain 10832 (also known as Wood-46), NRS071 (also known as Sanger 252), NRS100 (also known as COL), NRS382 (also known as strain 626), NRS384 (also known as LAC), NRS123 (also known as MW2), NRS001 (also known as Mu50), NRS072 (also known as Sanger 476), NRS102 (also known as Reynolds), NRS111 (also known as FR1913), NRS144 (also known as RN4220) and USA300. Other exemplary S. aureus stains include USA100, USA200, USA400 and USA500 types.

It is contemplated herein that the disclosed polyclonal antibody compositions bind at least 3 different S. aureus strains. For example, in exemplary embodiments, the disclosed polyclonal antibody compositions bind at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, or at least 12 different S. aureus strains, e.g., the strains identified in Table 4.

In one embodiment, an antibody provided herein competes with 5.6.H9 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 38 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 40 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.6.H9, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 22.18A.E9 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 173 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 175 for binding to one or more S. aureus. Exemplary strains for a competitive binding assay with 22.18A.E9, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.11.H10 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 11 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 13 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.11.H10, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.27.A11 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 20 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 22 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.27.A11, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.17.F8 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 47 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 49 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.17.F8, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.19.F12 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 56 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 58 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.19.F12, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.23.C9 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 65 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 67 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.23.C9, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.23.C12 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 74 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 76 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.23.C12, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 8.51.G11 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 83 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 85 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 8.51.G11, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 9.51.H9 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 92 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 94 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 9.51.H9, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 18.43.D8 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 101 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 103 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 18.43.D8, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 22.22.E7 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 110 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 112 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 22.22.E7, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 8.51.G10 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 149 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 151 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 8.51.G10, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.24A.A7 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 153 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 155 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.24A.A7, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.24A.F3 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 157 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 159 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.24A.F3, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.8B.H4 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 161 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 163 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.8B.H4, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 26.51.E1 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 165 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 167 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 26.51.E1, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 22.21.A7 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 169 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 171 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 22.21.A7, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.52.H1 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 177 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 179 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.52.H1, for example, under the conditions set forth in Example 4 are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.15.C1 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 181 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 183 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.15.C1, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.54.E6 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 185 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 187 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.54.E6, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.55.D2 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 189 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 191 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.55.D2, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 22.14.A1 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 193 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 195 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 22.14.A1, for example, under the conditions set forth in Example 4 are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 26.53.B4 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 197 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 199 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 26.53.B4, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.63.E2 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 201 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 203 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.63.E2, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 5.64.G4 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 205 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 207 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 5.64.G4, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 43.52.A11 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 209 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 211 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 43.52.A11, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 43.52.E12 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 213 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 215 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 43.52.E12, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another embodiment, an antibody provided herein competes with 43.62.E2 comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 217 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 219 for binding to one or more S. aureus strains. Exemplary strains for a competitive binding assay with 43.62.E2, for example, under the conditions set forth in Example 4, are set forth in Table 4.

In another aspect, isolated human antibodies are also disclosed (e.g., isolated, individual antibodies or antigen binding fragments thereof). Exemplary human antibodies include an isolated human antibodies that bind S. aureus delta-toxin. One exemplary antibody that binds S. aureus delta-toxin comprises CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 38 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 40 of 5.6.H9. Another exemplary antibody that bind S. aureus delta-toxin comprises CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 189 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 191 of 5.55.D2.

Also provided herein is an isolated human antibody that binds S. aureus phenol soluble modulin beta-1. The antibody comprises CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 173 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 175 of 22.18A.E9.

Additional exemplary isolated human antibodies disclosed herein include: a human antibody that binds one or more S. aureus strains comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 92 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 94 of 9.51.H9;

a human antibody that binds one or more S. aureus strains comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 11 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 13 of 5.11.H10;

a human antibody that binds one or more S. aureus strains comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 74 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 76 of 5.23.C12;

a human antibody that binds one or more S. aureus strains comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 177 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 179 of 5.52.H10;

a human antibody that binds one or more S. aureus strains comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 101 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 103 of 18.43.D8;

a human antibody that binds one or more S. aureus strains comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 149 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 151 of 8.51.G10; and

a human antibody that binds one or more S. aureus strains comprising CDR1, CDR2 and CDR3 of heavy chain amino acid sequence SEQ ID NO: 83 and CDR1, CDR2, CDR3 of light chain amino acid sequence SEQ ID NO: 85 of 8.51.G11.

Production of Antibodies

Methods for producing antibodies of the invention are known in the art. In certain embodiments, an anti-S. aureus polyclonal antibody composition may be produced from a single manufacturing cell line or a mixture of cell lines producing individual monoclonal antibodies. In other embodiments, DNA molecules encoding light chain variable regions and heavy chain variable regions can be chemically synthesized using the sequence information provided herein. Synthetic DNA molecules can be ligated to other appropriate nucleotide sequences, including, e.g., constant region coding sequences, and expression control sequences, to produce conventional gene expression constructs encoding the desired antibodies. Production of defined gene constructs is within routine skill in the art. Alternatively, the sequences provided herein can be cloned out of hybridomas or B-cells by conventional hybridization techniques or polymerase chain reaction (PCR) techniques, using synthetic nucleic acid probes whose sequences are based on sequence information provided herein, or prior art sequence information regarding genes encoding the heavy and light chains of human antibodies in hybridoma cells.

As disclosed herein, individual anti-S. aureus antibodies may be characterized by their variable region (V_Hand V_Lsequences) or by their heavy and light chain CDR sequences. Each antibody will have a pair of sequences if defined by its variable region sequences (i.e., V_Hand V_Lcognate pairs) or a set of sequences if defined by its CDR sequences (i.e., three heavy chain CDRs and three light chain CDRs). V_Hand V_Lpairs can be expressed as full-length antibodies, Fab fragments or other antibody fragments that have binding specificity to a S. aureus associated antigen. Specific V_Hand V_Lpairs are identified in Table 2 in Example 1. Specific heavy and light chain CDR sets are identified in Table 3 in Example 1.

Nucleic acids encoding desired antibodies (e.g., V_Hand V_Lpairs) can be incorporated (ligated) into expression vectors, which can be introduced into host cells through conventional transfection or transformation techniques. Exemplary host cells are E. coli cells, Chinese hamster ovary (CHO) cells, human embryonic kidney 293 (HEK 293) cells, HeLa cells, baby hamster kidney (BHK) cells, monkey kidney cells (COS), human hepatocellular carcinoma cells (e.g., Hep G2), and myeloma cells that do not otherwise produce IgG protein. Transformed host cells can be grown under conditions that permit the host cells to express the genes that encode the immunoglobulin light and/or heavy chain variable regions.

Specific expression and purification conditions will vary depending upon the expression system employed. For example, if a gene is to be expressed in E. coli, it is first cloned into an expression vector by positioning the engineered gene downstream from a suitable bacterial promoter, e.g., Trp or Tac, and a prokaryotic signal sequence. The expressed secreted protein accumulates in refractile or inclusion bodies, and can be harvested after disruption of the cells by French press or sonication. The refractile bodies then are solubilized, and the proteins refolded and cleaved by methods known in the art.

If the engineered gene is to be expressed in eukayotic host cells, e.g., CHO cells, it is first inserted into an expression vector containing a suitable eukaryotic promoter, a secretion signal, IgG enhancers, and various introns. This expression vector optionally contains sequences encoding all or part of a constant region, enabling an entire, or a part of, a heavy or light chain to be expressed. The gene construct can be introduced into eukaryotic host cells using convention techniques. The host cells express V_Lor V_Hfragments, V_L-V_Hheterodimers, V_H-V_Lor V_L-V_Hsingle chain polypeptides, complete heavy or light immunoglobulin chains, or portions thereof, each of which may be attached to a moiety having another function (e.g., cytotoxicity). In some embodiments, a host cell is transfected with a single vector expressing a polypeptide expressing an entire, or part of, a heavy chain (e.g., a heavy chain variable region) or a light chain (e.g., a light chain variable region). In other embodiments, a host cell is transfected with a single vector encoding (a) a polypeptide comprising a heavy chain variable region and a polypeptide comprising a light chain variable region, or (b) an entire immunoglobulin heavy chain and an entire immunoglobulin light chain. In still other embodiments, a host cell is co-transfected with more than one expression vector (e.g., one expression vector expressing a polypeptide comprising an entire, or part of, a heavy chain or heavy chain variable region, and another expression vector expressing a polypeptide comprising an entire, or part of, a light chain or light chain variable region).

The expression vector may also include constant regions for the heavy and/or light chain. It is contemplated that the choice of the constant region may vary for the individual antibodies included in the polyclonal composition. For example, it may be desirous to have IgG1 constant regions for certain antibodies and IgG2 constant regions for other antibodies depending on the desired effector function to clear or destroy antigen (e.g., ADCC, phagocytosis, increased complement activity (e.g., via the classic and/or alternative complement pathways), binding to mass cells and/or basinophiles). Heavy chain constant regions may be selected from the isotypes IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgD, and IgE. Light chain constant regions may be either kappa or lambda.

A polypeptide comprising an immunoglobulin heavy chain variable region or light chain variable region can be produced by growing a host cell transfected with an expression vector encoding such variable region, under conditions that permit expression of the polypeptide. Following expression, the polypeptide can be harvested and purified using techniques well known in the art, e.g., affinity tags such as glutathione-S-transferase (GST) and histidine tags.

A human antibody that binds to one or more S. aureus strains, or an antigen-binding fragment of the antibody, can be produced by growing a host cell transfected with: (a) an expression vector that encodes a complete or partial immunoglobulin heavy chain, and a separate expression vector that encodes a complete or partial immunoglobulin light chain; or (b) a single expression vector that encodes both chains, under conditions that permit expression of both chains. The intact antibody (or antigen-binding fragment) can be harvested and purified using techniques well known in the art, e.g., Protein A, Protein G, affinity tags such as glutathione-S-transferase (GST) and histidine tags. It is within ordinary skill in the art to express the heavy chain and the light chain from a single expression vector or from two separate expression vectors.

Use of Antibodies

Anti-S. aureus polyclonal antibodies as described herein can be used to treat one or more strains of S. aureus and/or prevent infection of one or more strains of S. aureus, including antibiotic resistant strains of S. aureus, e.g., penicillin-resistant strains, methicillin-resistant strains (MRSA) (e.g., community acquired MRSA (CA-MRSA), hospital-acquired MRSA (HA-MRSA)), vancomycin-resistant strains (VRSA), and vancomycin-intermediate resistant strains (VISA). The disclosed antibodies may also be used to treat methicillin-sensitive strains (e.g., MSSA). S. aureus infected host cells (e.g., mammalian host cells, e.g., human host cells) are exposed to a therapeutically effective amount of the antibody so as to inhibit infectivity of S. aureus by inhibiting growth and/or colonization, and/or by inducing phagocytosis, and/or killing the S. aureus. In some embodiments, the antibodies inhibit infectivity of S. aureus by at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 98%, 99%, or 100%.

In certain embodiments, individual human anti-S. aureus antibodies may be used to treat one or more strains of S. aureus and/or prevent infection of one or more strains of S. aureus.

As used herein, “treat”, “treating” and “treatment” mean the treatment of a disease in a mammal, e.g., in a human. This includes: (a) inhibiting the disease or infection, i.e., arresting its development or progression; (b) relieving the disease or infection, i.e., causing regression of the disease state or infection; and/or (c) curing the disease or infection.

Exemplary diseases that can be treated or prevented using the disclosed antibodies include, but are not limited to, invasive or toxigenic diseases associated with pathogenic S. aureus strains. Invasive diseases include pneumonia (e.g., S. aureus pneumonia), meningitis, Bacteremia, osteomyelitis, sepsis (e.g., septic arthritis, septic thrombophlebitis), and endocarditis (e.g., acute bacterial endocarditis). Toxic diseases include, but are not limited to, Staphylococcal food poisoning, scalded skin syndrome, and toxic shock syndrome (TSS). Additional examples of diseases and disorders that may be treated include skin abscesses, cellulitis, upper respiratory tract infections (e.g., otis media, bacterial trachetis, acute epiglottitis, thyroiditis), lower respiratory tract infections (e.g., empyema, lung abscess), heart, gastrointestinal (e.g., secretory diarrhea, splenic abscess, retroperitoneal abscess), CNS (e.g., cerebral abscess), eye (e.g., blepharitis, conjunctivitis, keratitis, endophthalmitis, preseptal and orbital cellulitis, darcryocystitis), kidney, urinary, skin (e.g., impetigo, folloculitis, cutaneous abscesses, cellulitis, wound infection, bacterial myositis), and bone and joint infections. It is contemplated herein that certain disorders associated with polymicrobial infections including a S. aureus infection may be treated or prevented using the disclosed antibodies. Exemplary disorders associated with polymicrobial infections (including S. aureus infections) include cystic fibrosis (e.g., infections with S. aureus and Pseudomonas), upper and lower respiratory tract infections, pneumonia, septicemia and skin infections.

Generally, a therapeutically effective amount of active component is in the range of 0.1 mg/kg to 100 mg/kg, e.g., 1 mg/kg to 100 mg/kg, 1 mg/kg to 10 mg/kg. In an exemplary embodiment, a human recombinant polyclonal antibody may be administered at 1 mg/kg. The amount administered will depend on variables such as the type and extent of disease or indication to be treated, the overall health of the patient, the in vivo potency of the antibody, the pharmaceutical formulation, and the route of administration. The initial dosage can be increased beyond the upper level in order to rapidly achieve the desired blood-level or tissue-level. Alternatively, the initial dosage can be smaller than the optimum, and the dosage may be progressively increased during the course of treatment. Human dosage can be optimized, e.g., in a conventional Phase I dose escalation study designed to run from 0.5 mg/kg to 20 mg/kg. Dosing frequency can vary, depending on factors such as route of administration, dosage amount and the disease being treated. Exemplary dosing frequencies are once per day, once every 2 days, once every three days, once every four days, once every five days, once every six days, once per week, once every two weeks, once every month, once every six months, and once a year. In some embodiments of the invention, dosing is once every two weeks. A preferred route of administration is parenteral, e.g., intravenous or subcutaneous. Formulation of antibody-based drugs is within ordinary skill in the art. In some embodiments of the invention, the antibody is lyophilized and reconstituted in buffered saline at the time of administration.

For therapeutic use, one or more disclosed antibodies, or an antigen binding fragments thereof, can be combined with a pharmaceutically acceptable carrier. As used herein, “pharmaceutically acceptable carrier” means buffers, carriers, and excipients suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. The carrier(s) should be “acceptable” in the sense of being compatible with the other ingredients of the formulations and not deleterious to the recipient. Pharmaceutically acceptable carriers include buffers, solvents, dispersion media, coatings, isotonic and absorption delaying agents, and the like, that are compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is known in the art.

Pharmaceutical compositions containing one or more of the disclosed antibodies can be presented in a dosage unit form and can be prepared by any suitable method. A pharmaceutical composition should be formulated to be compatible with its intended route of administration. Examples of routes of administration are intravenous (IV), intradermal, inhalation, transdermal, topical, transmucosal, and rectal administration. An exemplary route of administration for monoclonal antibodies is IV infusion. Useful formulations can be prepared by methods well known in the pharmaceutical art. For example, see Remington's Pharmaceutical Sciences, 18th ed. (Mack Publishing Company, 1990). Formulation components suitable for parenteral administration include a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl paraben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as EDTA; buffers such as acetates, citrates or phosphates; and agents for the adjustment of tonicity such as sodium chloride or dextrose.

For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor ELTM (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). The carrier should be stable under the conditions of manufacture and storage, and should be preserved against microorganisms. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyetheylene glycol), and suitable mixtures thereof.

Pharmaceutical formulations preferably are sterile. Sterilization can be accomplished, for example, by filtration through sterile filtration membranes. Where the composition is lyophilized, filter sterilization can be conducted prior to or following lyophilization and reconstitution.

EXAMPLES

The following Examples are merely illustrative and are not intended to limit the scope or content of the invention in any way.

Example 1
Sequence Analysis of Anti-S. aureus Antibodies

This example describes the sequence analysis of the anti-S. aureus antibodies disclosed herein.

Individual anti-S. aureus antibodies were isolated from human donor individuals (e.g., healthy individuals) who had been exposed to S. aureus including the S. aureus strains methicillin sensitive S. aureus (MSSA), hospital-acquired-MRSA, and community-acquired-MRSA. The individual antibodies (e.g., V_Hand V_Lregions) were sequenced by Sanger dideoxy-sequencing and were analyzed using IMGT/V-Quest software (Montpellier, France) to identify and confirm variable region sequences.

The nucleic acid sequences encoding and the protein sequences defining heavy and light chain variable regions of the anti-S. aureus antibodies are shown below (amino terminal signal peptide sequences are not shown). CDR sequences (IMGT definition) are indicated by bold font and underlining in the nucleic acid and amino acid sequences.

Nucleic Acid Sequence Encoding the 1.62.B9 Heavy Chain Variable Region (SEQ ID NO: 1)

Protein Sequence Defining the 1.62.B9 Heavy Chain Variable Region (SEQ ID NO: 2)

EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMTWVRQAPGKGLEWVGR

IKSKTDGGTT
DYAAPVKGRFTISRDDSINTLYLQMNSLKTEDTAVYYCRT

GGYW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 1.62.B9 Lambda Chain Variable Region (SEQ ID NO: 3)

Protein Sequence Defining the 1.62.B9 Lambda Chain Variable Region (SEQ ID NO: 4)

QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYPYWFQQKPGQAPRTLI

YDTSKKHSWTPARFSGSLLGGKAALTLSGAQPEDEAEYYCLVSDSGARIF

GPGTKVTVL

Nucleic Acid Sequence Encoding the 5.11.H10 Heavy Chain Variable Region (SEQ ID NO: 10)

Protein Sequence Defining the 5.11.H10 Heavy Chain Variable Region (SEQ ID NO: 11)

QVQLVQSGPEMKKPGASVKVSCQASGYTFTINGISWVRQAPGQRPEWMGW

ISTSNGQT
NFAQNFQGRLTLTTDTSTTTAFMELMSLTSADTAVYYCARNP

YGNSRRFFDYW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.11.H10 Kappa Chain Variable Region (SEQ ID NO: 12)

Protein Sequence Defining the 5.11.H10 Kappa Chain Variable Region (SEQ ID NO: 13)

DIQMTQSPSSLSASVGDRVIITCRTSQTITNYINWYQQKPGKAPQLLIYG

VS
SLQSGVPSRFSGGGSGTEFTLTISSLQPEDFATYYCQQSYRAPQTFGQ

GTKLEIK

Nucleic Acid Sequence Encoding the 5.27.A11 Heavy Chain Variable Region (SEQ ID NO: 19)

Protein Sequence Defining the 5.27.A11 Heavy Chain Variable Region (SEQ ID NO: 20)

EVQLVESGGGLVQPGGSLRLSCAASGFAFSSHEMHWVRQGIGHSLEWVSA

IGLAGDT
YYSDSVKGRFTISRENAKNTLYLEMNNLRVGDTAVYYCVKEGA

HWEFDSW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.27.A11 Lambda Chain Variable Region (SEQ ID NO: 21)

Protein Sequence Defining the 5.27.A11 Lambda Chain Variable Region (SEQ ID NO: 22)

QSVLTQPPSVSGAPGQRVIISCTGSSSNLGASLDVHWYQRLPGTGPRLLI

YANNNRPSGVPDRFSGSKSGTSASLAITGLQAEDEGDYYCQSYDGSLRVF

GGGTRLTVL

Nucleic Acid Sequence Encoding the 5.6.H2 Heavy Chain Variable Region (SEQ ID NO: 28)

Protein Sequence Defining the 5.6.H2 Heavy Chain Variable Region (SEQ ID NO: 29)

QVQLVESGGGLFKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWISY

ISSSGRTI
KYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDG

GYCGSANCLHDAFDIW
GQGTMVTVSS

Nucleic Acid Sequence Encoding the 5.6.H2 Kappa Chain Variable Region (SEQ ID NO: 30)

Protein Sequence Defining the 5.6.H2 Kappa Chain Variable Region (SEQ ID NO: 31)

DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYK

AS
SLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSTFGQG

TKVEIK

Nucleic Acid Sequence Encoding the 5.6.H9 Heavy Chain Variable Region (SEQ ID NO: 37)

CAGGTCACCTTGAAGGAGTCTGGTCCCACGCTGGTGAAACCCACACAGAC

CCTCACGCTGACGTGCACCTTCTCTGGGTTTTCGCTCAGCACTAGTGGAG

AGGGT
GTGGCCTGGATCCGTCAGGCCCCAGGAAAGGCCCTGGAGTGGCTT

GCACTCATTTATTGGGATGATGATAAGCGCTACAACCCATCTCTGAAGAG

CAGGCTCACCATCACCAAGGACAACTCCAGAAACCAAGTGGTCCTTACAA

TGACCAACATGGACCCTGTGGACACAGCCACATATTACTGTGTACACAGG

GGGATGAATAGGGTTTTTGGGGTAGTTTATAATTCGGGCTGGTTCGACCC

CTGG
GGCCAGGGAACCCTGGTCACCGTCTCGAGTG

Protein Sequence Defining the 5.6.H9 Heavy Chain Variable Region (SEQ ID NO: 38)

QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTSGEGVAWIRQAPGKALEWL

ALIYWDDDKRYNPSLKSRLTITKDNSRNQVVLTMTNMDPVDTATYYCVHR

GMNRVFGVVYNSGWFDPW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.6.H9 Kappa Chain Variable Region (SEQ ID NO: 39)

Protein Sequence Defining the 5.6.H9 Kappa Chain Variable Region (SEQ ID NO: 40)

EIVLTQSPGTLSLSPGERATLSCRASQSVRSSQLAWYQQKPGQAPSLLMY

DAS
KRATGIPDRFSGSGSGTDFTLTISRLEPEDFVVYFCQQYDTSPWTFG

QGTKVEIK

Nucleic Acid Sequence Encoding the 5.17.F8 Heavy Chain Variable Region (SEQ ID NO: 46)

CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGAC

CCTGTCCCTCAGTTGCGCTGTCTCCGGTACGTCCTTCAGTGATTACTACT

GGGCCTGGATCCGTCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGGAA

ATCAATCAGAGTGGACACACT
AACGACAACCCGTCCTTCAAGAGTCGAGT

CACCATGTTAGTAGACAAGTCCAAGAACCAGTTCTCCCTGAGGATGACTT

CTGTGACCGCCGCGGACACGGCTGTATATTACTGTGCGAGATTTCCTTGG

GTGGGACCCGAGGGTTTTGACCACTGG
GGCCAGGGAACCCTGGTCACCGT

CTCGAGTG

Protein Sequence Defining the 5.17.F8 Heavy Chain Variable Region (SEQ ID NO: 47)

QVQLQQWGAGLLKPSETLSLSCAVSGTSFSDYYWAWIRQPPGKGLEWIGE

INQSGHT
NDNPSFKSRVTMLVDKSKNQFSLRMTSVTAADTAVYYCARFPW

VGPEGFDHW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.17.F8 Kappa Chain Variable Region (SEQ ID NO: 48)

GAAATTGTGCTGACTCAGTCTCCAGACTTTCAGTCTGGGACTCCAAAGGA

GATGGTCACCATCACCTGCCGGGCCAGTCAGACCATTGGTAACAGCTTAC

ACTGGTACCAACAGAAACCAGGTCAGTCTCCAAAGCTCCTCATCAAATAT

GGTTCC
CAGTCCATGTCAGGGGTCCCCTCGCGGTTCAGTGGCAGTGGATT

TGGGACAGATTTCACCCTGACCATCAACAGCCTGGAAGCTGAAGATGCTG

CAGTGTATTACTGTCTTCAGAGTGGTGGTTTTCCGTGGACGTTCGGCCAA

GGGACCAAGGTGGAGATCAGACGAACTGTGGCTGCACCATCTGTCTTCAT

CTTCCCGCCATCTGATGAGCAGTTGAAATCTG

Protein Sequence Defining the 5.17.F8 Kappa Chain Variable Region (SEQ ID NO: 49)

EIVLTQSPDFQSGTPKEMVTITCRASQTIGNSLHWYQQKPGQSPKLLIKY

GS
QSMSGVPSRFSGSGFGTDFTLTINSLEAEDAAVYYCLQSGGFPWTFGQ

GTKVEIR

Nucleic Acid Sequence Encoding the 5.19.F12 Heavy Chain Variable Region (SEQ ID NO: 55)

CAGGTCCAGCTGGTACAGTCTGGGGCTGAGATGAAGAAGCCTGGGGCCTC

AGTGAAGGTCTCCTGCAAGGGTTCCGGATCCAGTCTCCCTTATCTTTCGA

TACAATGGGTGCGACAGGCCCCTGGAAAAGGCCTTGAGTGGATGGGAGGC

TTTGATCCTGAAGACGGTGAAACA
ATCTACAACGAGAAATTCGAGGGCAG

AATCACCATGGCCGAGGACACATCGACAGACACAGCCTACATGGAACTCA

GCAGCCTCACATCTGACGACACGGCCGTCTATTATTGCGCAACAAGCCTC

ATCCGTAACGGTCTTTATGAAGCGTTCGAACACTGG
GGCCAGGGAACCCT

GGTCACCGTCTCGAGTG

Protein Sequence Defining the 5.19.F12 Heavy Chain Variable Region (SEQ ID NO: 56)

QVQLVQSGAEMKKPGASVKVSCKGSGSSLPYLSIQWVRQAPGKGLEWMGG

FDPEDGET
IYNEKFEGRITMAEDTSTDTAYMELSSLTSDDTAVYYCATSL

IRNGLYEAFEHW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.19.F12 Kappa Chain Variable Region (SEQ ID NO: 57)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGA

CAGAGTCACCATCACTTGCCAGGCGAGTGATGACATTAAAAAGAATTTAA

ATTGGTATCAACAAAAAACAGGGACAGCCCCTAAGCTCCTGGTCTACGAC

GCATCC
AATTTGGAGACAGGGGTCCCATCGAGGTTCCGTGGACGTGCATC

TGGGACACAATATACTTTCACCATCACGAATCTGCAGCCTCAAGATTCTG

GAATATATTACTGTCAACAATATGACAATGTCCCGCTCAGTTTTGGCGGA

GGGACCAAGGTGGAGGTCAGAC

Protein Sequence Defining the 5.19.F12 Kappa Chain Variable Region (SEQ ID NO: 58)

DIQMTQSPSSLSASVGDRVTITCQASDDIKKNLNWYQQKTGTAPKLLVYD

AS
NLETGVPSRFRGRASGTQYTFTITNLQPQDSGIYYCQQYDNVPLSFGG

GTKVEVR

Nucleic Acid Sequence Encoding the 5.23.C9 Heavy Chain Variable Region (SEQ ID NO: 64)

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGATGCCTGAGTCCTC

GGTGAGGGTCTCCTGCAGGATTTCTGGAGGCAACTTCAAAAATTATATTT

TTAACTGGGTGCGACAGGCCCCCGGACAAGGGCTTGAGTGGGTTGGAAGG

ATCAACCCAAAAGTTGGAAATGAA
AATCACATACAGAGATATGGGAACAG

ACTCACCCTCACCGCGGACGATTCCAGGAGAACAGTTTACATGGAGTTGA

GCAGCCTGACAACAGACGACACGGCCGTATATTATTGTGCGACATTACGT

GTTATTGGTAACCGGAGACTACGACCGGTGGGCGGAATTTTTGATATCTG

G
GGCCAAGGGACAATGGTCACCGTCTCGAGTG

Protein Sequence Defining the 5.23.C9 Heavy Chain Variable Region (SEQ ID NO: 65)

QVQLVQSGAEVKMPESSVRVSCRISGGNFKNYIFNWVRQAPGQGLEWVGR

INPKVGNE
NHIQRYGNRLTLTADDSRRTVYMELSSLTTDDTAVYYCATLR

VIGNRRLRPVGGIFDIW
GQGTMVTVSS

Nucleic Acid Sequence Encoding the 5.23.C9 Kappa Chain Variable Region (SEQ ID NO: 66)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCGTCTGTGGGAGA

CAGAGTCACCATCACTTGCCAGGCGAGTCAGGACGTGAGTCACTATGTAA

ATTGGTATCAACAAAAACCAGGGAAAGCCCCAAAAGCCCTGGTCTACGAG

GCATCC
AATTTGGAAACAGGGGTCCCATCAAGATTCAGTGGAAGTGGATC

TGGGACACATTTCACCTTCACCATCAACAGCCTGCAGCCTGAAGATATCG

CGACTTATTTCTGTCAACATGATGCAGAGCTGCCTCCCTCTTTCGGAGGA

GGGACCAAGGTGGAGATCAAAC

Protein Sequence Defining the 5.23.C9 Kappa Chain Variable Region (SEQ ID NO: 67)

DIQMTQSPSSLSASVGDRVTITCQASQDVSHYVNWYQQKPGKAPKALVYE

AS
NLETGVPSRFSGSGSGTHFTFTINSLQPEDIATYFCQHDAELPPSFGG

GTKVEIK

Nucleic Acid Sequence Encoding the 5.23.C12 Heavy Chain Variable Region (SEQ ID NO: 73)

CAGGTTCAGCTGGTGCAGTCTGGAGCTGAAGTGAAGAAGCCTGGGGCCT

CAGTGAAGGTCTCCTGCAAGTCTTCTGGTCACTCCTTTACCGCCTATG

GC
ATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGG

GGTGGATCAGCACTAACAATGGCAACACAAACTATAGAGAGAAGTTC

CAGGACAGACTCTCCTTGACCACGGACACATCCACGAGCACAGTCTACA

TGGAACTGAGGAGCCTGACATCTGACGACACGGCCGTGTATTACTGTG

CGAGAAATCCTTATGGCAATTCGCGGAGATTCTTAGACTACTGG
GGCC

AGGGAACCCTGGTCACCGTCTCGAGTG

Protein Sequence Defining the 5.23.C12 Heavy Chain Variable Region (SEQ ID NO: 74)

QVQLVQSGAEVKKPGASVKVSCKSSGHSFTAYGISWVRQAPGQGLEW

MGWISTNNGNTNYREKFQDRLSLTTDTSTSTVYMELRSLTSDDTAVY

YCARNPYGNSRRFLDYWGQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.23.C12 Kappa Chain Variable Region (SEQ ID NO: 75)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTCGGAG

ACAGAGTCATCATCACTTGCCGGGCAAGTCAGAACATTAGCCCCTAT

TTAAATTGGTATCAGCAGAAGCCAGGGAGAGCCCCTGAGCTCCTGATCT

ATGGTACGACCACTGTACAAACTGGGGTCCCGTCACGGTTCAGTGGC

ATTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTG

AAGATTTTGCAACTTATTACTGTCAACAGAGCTACAGGGCCCCTCAAA

CGTTC
GGCCAAGGGACCAAGGTGGAAGTCAAGC

Protein Sequence Defining the 5.23.C12 Kappa Chain Variable Region (SEQ ID NO: 76)

DIQMTQSPSSLSASVGDRVIITCRASQNISPYLNWYQQKPGRAPELL

IYGTTTVQTGVPSRFSGIGSGTDFTLTISSLQPEDFATYYCQQSYR

APQTF
GQGTKVEVK

Nucleic Acid Sequence Encoding the 8.51.G11 Heavy Chain Variable Region (SEQ ID NO: 82)

CAGGTCACCTTGAAGGAGTCTGGTCCTCCGCTGGTGAATCCCACAGAGA

CCCTCACGGTGACCTGCAATTTCCCTGGCTTCTCATTCACCTCTAGTG

GAGAGGGT
GTGGGCTGGATCCGTCAGCCCCCAGGAAAGGCCCTGGAAT

GGCTTGCTCACATTTATTGGGATGGCGATAAGCGGTTCAACACATCT

CTGAAAAACAGACTCAACATCACCAAGGACACCTCTAAGAATCAGGTGG

TCCTCACTTTGACCAACGTGGCCCCTGTGGACACAGCCACGTATTTCT

GTGTCCACCTGACACGCCCATCCTTTTGGAGTCCCTATTACCTTTTTGA

CCTCTGG
GGCCAGGGAACCCTGGTCACCGTCTCGAGTG

Protein Sequence Defining the 8.51.G11 Heavy Chain Variable Region (SEQ ID NO: 83)

QVTLKESGPPLVNPTETLTVTCNFPGFSFTSSGEGVGWIRQPPGKALE

WLAHIYWDGDKRFNTSLKNRLNITKDTSKNQVVLTLTNVAPVDTATYF

CVHLTRPSFWSPYYLFDLW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 8.51.G11 Kappa Chain Variable Region (SEQ ID NO: 84)

GACATCCAGTTGACCCAGTCTCCGCCCTCCCTGTCTGCATCTGTCGGAG

ACAGTGTCACCATAACTTGCCGGGCAAGTCAATATATTAGTACGTAT

TTAAATTGGTATCAGCAGAAACCGGGGAAAGCCCCCAGACTCTTGATC

TATGGTGCATCCAATTTGCACAGTGGGGTCTCATCAAGGTTCAGTG

GCAGTAGATCTGGGACAGATTTCACTCTCACCATAACCAGTCTACAGC

CTGAAGATTTTGCGACTTACTACTGCCAACAGAGTTCCACTTTGTGG

TCGTTC
GGCCAAGGGACCAAGGTGGAGATGCACC

Protein Sequence Defining the 8.51.G11 Kappa Chain Variable Region (SEQ ID NO: 85)

DIQLTQSPPSLSASVGDSVTITCRASQYISTYLNWYQQKPGKAPRLL

IYGASNLHSGVSSRFSGSRSGTDFTLTITSLQPEDFATYYCQQSST

LWSF
GQGTKVEMH

Nucleic Acid Sequence Encoding the 9.51.H9 Heavy Chain Variable Region (SEQ ID NO: 91)

CAGGTTCAGCTGGTGCAGTCTGGAGGTGAAATGAGGAAACCTGGGGCCT

CATTGAAGGTCTCCTGCAAGGCCTCTAATTACACCTTCACCAGTTTTG

GT
CTGACCTGGCTGCGACAGGCCCCTGGGCAAGGCCCTGAGTGGCTGG

GCTGGATCAGTCCTTATAATGGAAACACCAACTATGCACAGAACTTC

CGCGACAGACTCACCATGACCACAGACACGTCCACGAGCACAGCCTACA

TGGAGCTGAAGAGCCTGACATCTGACGACACGGCCGTCTATTACTGTG

CCAGAACTAACTGGGGGAATTGGTACCTCGATCTCTGG
GGCCCTGG

CACCCTGGTCACTGTCTCGAGTG

Protein Sequence Defining the 9.51.H9 Heavy Chain Variable Region (SEQ ID NO: 92)

QVQLVQSGGEMRKPGASLKVSCKASNYTFTSFGLTWLRQAPGQGPEW

LGWISPYNGNTNYAQNFRDRLTMTTDTSTSTAYMELKSLTSDDTAVY

YCARTNWGNWYLDLWGPGTLVTVSS

Nucleic Acid Sequence Encoding the 9.51.H9 Kappa Chain Variable Region (SEQ ID NO: 93)

GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGGCTCTGGGCG

AGCGGGCCACCATCAGCTGCAAGTCCAGCCAGACTATCTTGTTCGGCT

CCAACAACAAGAACTAC
TTACAGTGGTTTCAGCAGAAACCCGGACAGC

CTCCTAAGTTACTCATTTACTGGGCATCTACCCGGGAATCCGGGGTC

CCTGACCGATTCAGTGGCGACGGGTCTGGGACAGACTTCACTCTCTCCA

TCGACAACCTACAGGCTGAAGATGTGGCACTTTATTATTGCCAGCAAT

ATTTTAGTAATCCGTATACTTTC
GGCCAGGGGACCAAATTGGAGATCA

AAC

Protein Sequence Defining the 9.51.H9 Kappa Chain Variable Region (SEQ ID NO: 94)

DIVMTQSPDSLAVALGERATISCKSSQTILFGSNNKNYLQWFQQKPG

QPPKLLIYWASTRESGVPDRFSGDGSGTDFTLSIDNLQAEDVALYY

CQQYFSNPYTF
GQGTKLEIK

Nucleic Acid Sequence Encoding the 18.43.D8 Heavy Chain Variable Region (SEQ ID NO: 100)

CAGGTCCAGCTTGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCT

CAGTGAAAATTGCCTGCAAGACCTCTGGATACATCTTCGTTGACTATG

CT
GTACAATGGGTGCGCCAGGCCCCCGGACAGAGGCTTGAGTGGATGG

GGTGGCTCCAGTCAGCCAGTGGCAAGACGAGCTCGTCACATAGTCTC

CAAGACAGAGTCTCCATTACCCGGGACACATCCGCGAACACAGCCTACT

TGGAACTGAGGAGTCTGACTTCTGAAGATACGGCTGTCTACTACTGTG

CGAGAGGGAGTATAAGTCATTACGCCCCCTTTGACTACTGG
GGCCAGG

GAACCCTGGTCACCGTCTCGAGTG

Protein Sequence Defining the 18.43.D8 Heavy Chain Variable Region (SEQ ID NO: 101)

QVQLVQSGAEVKKPGASVKIACKTSGYIFVDYAVQWVRQAPGQRLEW

MGWLQSASGKTSSSHSLQDRVSITRDTSANTAYLELRSLTSEDTAVY

YCARGSISHYAPFDYWGQGTLVTVSS

Nucleic Acid Sequence Encoding the 18.43.D8 Kappa Chain Variable Region (SEQ ID NO: 102)

GACATCGTGATGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCG

AGAGGGCCACCATCGACTGCAAGTCCAGTCAGAATATTTTATATACTT

CCAACAATAAGAGTTTC
TTAGCTTGGTACCAACAGAAACCAGGACAGC

CTCCTAAATTGCTCATTTACTGGGCGTCTACCCGAGAGTTCGGGGTC

CCTGCGCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCA

TCAACAACCTGCAGGGTGAAGATGTGGCCATTTATTACTGTCAACAGT

ATTTTTCTACTCCATACACTTTT
GGCCAGGGGACCAAGCTGGAGATCA

AAC

Protein Sequence Defining the 18.43.D8 Kappa Chain Variable Region (SEQ ID NO: 103)

DIVMTQSPDSLAVSLGERATIDCKSSQNILYTSNNKSFLAWYQQKPGQP

PKLLIYWASTREFGVPARFSGSGSGTDFTLTINNLQGEDVAIYYCQQYF

STPYTF
GQGTKLEIK

Nucleic Acid Sequence Encoding the 22.22.E7 Heavy Chain Variable Region (SEQ ID NO: 109)

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCCTCGGAGA

CCCTGTCCCTCACGTGCACTGTCTCTGGTGCCTACATCACTAATGACTAC

TGGAGCTGGATCCGGCAGCCCGCCGGGAAGGGACTGGCGTGGATTGGGCGT

CTCTATACCAGTGGGAGCACC
AACTACAACCCCTCCCTCAAGAGTCGAG

TCACCATGTCAGTAGACACGTCCAAAAACCAGTTCTCCCTGAGGCTCAC

CTCTGTGACCGCCGCGGACACGGCCGTTTATTATTGTGCGAGAGATGAG

TGTAGTGGTGGTGGGTGCTTCCATGAGAACTGG
GGCCAGGGAACCCTGG

TCACCGTCTCGAGTG

Protein Sequence Defining the 22.22.E7 Heavy Chain Variable Region (SEQ ID NO: 110)

QVQLQESGPGLVKPSETLSLTCTVSGAYITNDYWSWIRQPAGKGLAWIG

RLYTSGSTNYNPSLKSRVTMSVDTSKNQFSLRLTSVTAADTAVYYCARDE

CSGGGCFHENW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 22.22.E7 Kappa Chain Variable Region (SEQ ID NO: 111)

GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGG

AAAGAGCCACCCTCTCCTGCAGGGCCAGCCAGAGTATTAGCAGCAGCTA

C
TTGGCCTGGTACCAGCAGAAGCGTGGCCAGGCTCCCAGGCTCCTCATC

TATGGTGCATCCAGTAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCA

GTGGGACTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA

CGATTTTGCACTTTATTACTGTCAGCAGTATGATAGGTCACCGCTCACT

TTC
GGCGGAGGGACCAAGGTGGAGATCAAAC

Protein Sequence Defining the 22.22.E7 Kappa Chain Variable Region (SEQ ID NO: 112)

EIVLTQSPGTLSLSPGERATLSCRASQSISSSYLAWYQQKRGQAPRLLI

YGASSRATGIPDRFSGSGTGTDFTLTISRLEPDDFALYYCQQYDRSPLT

F
GGGTKVEIK

Nucleic Acid Sequence Encoding the 8.51.G10 Heavy Chain Variable Region (SEQ ID NO: 148)

CAGATCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAACCCCACACAGA

CCCTCACGCTGACCTGCACCTTTTCTGGGTTCTCATTCACCTCTAGTGG

AGAGGCT
GTGGGCTGGATCCGTCAGCCCCCAGGAAAGGCCCTGGAATGG

CTTGCTCACATTTATTGGGATGATGATCCGCGTTATAGTACATCTCTGA

AGAGCAGACTCACCATCACCAAGGACACCTCCAAAAATCAGGTGGTCCT

CTCTATGACCGACATTGACCCTGCGGACACAGGCACATATTACTGTGCA

CACCTGAGACGCCCATCCCTTTGGAGTCCTTATTATCTTTTTGACTGCT

GG
GGCCAGGGAACCCTGGTCACCGTCTCGAGTG

Protein Sequence Defining the 8.51.G10 Heavy Chain Variable Region (SEQ ID NO: 149)

QITLKESGPTLVNPTQTLTLTCTFSGFSFTSSGEAVGWIRQPPGKALEW

LAHIYWDDDPRYSTSLKSRLTITKDTSKNQVVLSMTDIDPADTGTYYCA

HLRRPSLWSPYYLFDCW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 8.51.G10 Kappa Chain Variable Region (SEQ ID NO: 150)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTTGGAG

ACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGTATTAGTAGCTATTT

AAATTGGTATCAACTGAAACCAGGACAAGCCCCTAAGCTCCTGATCTAT

GGTGCATCC
AGTTTGGAAAATGGGGTCCCTTCACGGTTCAGTGGCAGTG

GCTCTGGGCCAGATTTCACTCTCACCATTAGCAGTCTGCAACCTGAAGA

TTTTGCAACTTACTACTGTCAACAGAGTTACAAAATGTGGTCATTCGGC

CAAGGGACCAAGGTGGAAATCCAAC

Protein Sequence Defining the 8.51.G10 Kappa Chain Variable Region (SEQ ID NO: 151)

DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQLKPGQAPKLLIY

GAS
SLENGVPSRFSGSGSGPDFTLTISSLQPEDFATYYCQQSYKMWSF

GQGTKVEIQ

Nucleic Acid Sequence Encoding the 5.24A.A7 Heavy Chain Variable Region (SEQ ID NO: 152)

Protein Sequence Defining the 5.24A.A7 Heavy Chain Variable Region (SEQ ID NO: 153)

QVQLVQSGVEVKKPGASVKVSCKASGYTFTNFGFSWVRQAPGQGLEWLG

WINTHNGNTNYAPRFQDRVTLTTDTSTTTAYMELRSLRSEDTAVYYCA

RDLGGSSSAYW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.24A.A7 Kappa Chain Variable Region (SEQ ID NO: 154)

Protein Sequence Defining the 5.24A.A7 Kappa Chain Variable Region (SEQ ID NO: 155)

EIVLTQSPGTLSLSPGERATLSCRASHSGTNNYIAWYQQKPGQPPRLLI

YGASSRAPGISERFSGSGSGTDFTLIISRLEPEDFGVYYCEQYGNSPLT

F
GQGTKVEIK

Nucleic Acid Sequence Encoding the 5.24A.F3 Heavy Chain Variable Region (SEQ ID NO: 156)

Protein Sequence Defining the 5.24A.F3 Heavy Chain Variable Region (SEQ ID NO: 157)

QVQLQESGPGLVESSDVLSLTCTVSGGSISNDYWAWIRQTPGKGLEWIG

SVYYSGRTSFSPSLKSRVTMSVDTTKNQFFLNLGSLTVADTAVYYCART

TRLSFDWLVHYYGMDVW
GQGTTVTVSS

Nucleic Acid Sequence Encoding the 5.24A.F3 Kappa Chain Variable Region (SEQ ID NO: 158)

Protein Sequence Defining the 5.24A.F3 Kappa Chain Variable Region (SEQ ID NO: 159)

DIQMTQSPSSLTASVGDRVTIICRASQPIGSYLNWYQQSPGKAPKLLIYA

AS
TLQSGVPSRFSGSGSGTDFTLNISGLQPEDFATYYCQQSYNNPLFTFG

PGTKVDIK

Nucleic Acid Sequence Encoding the 5.8B.H4 Heavy Chain Variable Region (SEQ ID NO: 160)

Protein Sequence Defining the 5.8B.H4 Heavy Chain Variable Region (SEQ ID NO: 161)

EVQLVESGGSLVRPGGSLRLSCAASGFIFDDYGMSWVRQVPGEGLEWVAG

ITWDGVNT
DYADSVKGRFTISRDNAKNSLFLLMNSLRAEDTALYHCARAR

YYQGTGLRSYLDEW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.8B.H4 Kappa Chain Variable Region (SEQ ID NO: 162)

Protein Sequence Defining the 5.8B.H4 Kappa Chain Variable Region (SEQ ID NO: 163)

DIQMTQSPSSVSASVGERVTITCRATQGIDNWLAWYQHKPGKAPKLLIYA

AS
TLQSGVPSRFSGSGSGTDFTLTISSVQPEDVATYFCQQAKNFPRGGFT

F
GPGTKVALK

Nucleic Acid Sequence Encoding the 26.51.E1 Heavy Chain Variable Region (SEQ ID NO: 164)

Protein Sequence Defining the 26.51.E1 Heavy Chain Variable Region (SEQ ID NO: 165)

QVQLVESGGGVVQPGRSLRLSCAASGFTFSKFAMHWVRQAPGKGLEWVAA

IASDGYNK
YYADSVKGQFTVSRDTSRNTLYLQMDSLRPDDTAIYYCAYGH

LSFWFDPW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 26.51.E1 Kappa Chain Variable Region (SEQ ID NO: 166)

Protein Sequence Defining the 26.51.E1 Kappa Chain Variable Region (SEQ ID NO: 167)

DIQMTQSPSSLSASVGDRVTITCRASQDIGNGLGWYQQIPGKAPKRLIYA

AS
SLQSGVPSRFSGSGSGTEFTLTIHSLQPEDFATYYCLQHNFYPRTFGQ

GTKLEIK

Nucleic Acid Sequence Encoding the 22.21.A7 Heavy Chain Variable Region (SEQ ID NO: 168)

Protein Sequence Defining the 22.21.A7 Heavy Chain Variable Region (SEQ ID NO: 169)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIHWVRQAPGQGLEWMGW

INPYSGGT
NYAPKFQGRFTMARDTSITTTYLDLGRLTSSDTAIYFCARDF

FRAAAGTAGDYW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 22.21.A7 Kappa Chain Variable Region (SEQ ID NO: 170)

GACATCGTGATGACCCAGTCTCCAGAAGACTCCCTGGCTGTGTCTCTGGG

CGAGAGGGCCACCATCAACTGCTCCAGCCAGAGTGCTTTATACAGCCCCA

GCAGTAAGACCTAC
TTAGCTTGGTACCAGCAGAGACCGGGACACCCTCCT

AAGCTTCTCATTTACTGGGCATCTACCCGGGTATCCGGGGTCCCTGACCG

ATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCGGCAGCC

TGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGTACTATTATGGTACT

GTCACTTTC
GGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGC

ACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTG

Protein Sequence Defining the 22.21.A7 Kappa Chain Variable Region (SEQ ID NO: 171)

ADIVMTQSPDSLAVSLGERATINCSSQSALYSPSSKTYLAWYQQRPGHPP

KLLIYWASTRVSGVPDRFSGSGSGTDFTLTIGSLQAEDVAVYYCQYYYGT

VTF
GGGTKVEIK

Nucleic Acid Sequence Encoding the 22.18A.E9 Heavy Chain Variable Region (SEQ ID NO: 172)

Protein Sequence Defining the 22.18A.E9 Heavy Chain Variable Region (SEQ ID NO: 173)

QVQLQESGPRLVKPSETLSLTCTVSGGSINSYYWSWIRQPVGKGLEWIGR

MYPGGTS
SYNSSLKSRVIMSVDTSKNQFSLNLTSVTAADTAVYFCARDPT

YHHGTSGYVGTFDLW
GQGTMVTVSS

Nucleic Acid Sequence Encoding the 22.18A.E9 Kappa Chain Variable Region (SEQ ID NO: 174)

GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGCGTCTCCAGGGG

AAAGAGTCACCCTCTCCTGCAGGGCCAGTCCGAGTGTTCGCAACAATTT

AGCCTGGTACCAGCAGAAACCTGGCCAGCCTCCTAGGCTCCTCATCTAT

GGTGCATCC
ACCAAGGTCATGGGTACTCCAACCAGGTTCAGTGGCAGTG

GGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGA

TTTTGCAGTTTATTACTGTCAGCAGTATAATAGCTGGCCTCCGTACACT

TTT
AGCCAGGGGACCAAACTGGAGATCAAACGAACTGTGGCTGCACCAT

CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTG

Protein Sequence Defining the 22.18A.E9 Kappa Chain Variable Region (SEQ ID NO: 175)

DIVMTQSPATLSASPGERVTLSCRASPSVRNNLAWYQQKPGQPPRLLIY

GAS
TKVMGTPTRFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNSWPPYT

F
SQGTKLEIK

Nucleic Acid Sequence Encoding the 5.52.H10 Heavy Chain Variable Region (SEQ ID NO: 176)

Protein Sequence Defining the 5.52.H10 Heavy Chain Variable Region (SEQ ID NO: 177)

EVQLVESGGGLVRPGESLRLSCAGSGFTFSMFTLNWVRQAPGKGLEWVA

SISGSSSLVFHEDSVKGRFTISRDNAKNSVYLQMNSLRAEDTAIYYCVR

GDSRDYW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.52.H10 Kappa Chain Variable Region (SEQ ID NO: 178)

Protein Sequence Defining the 5.52.H10 Kappa Chain Variable Region (SEQ ID NO: 179)

QSVLTQPPSVSAAPGQKVTISCSGRTSNIGNNHVSWYQQFPGTAPKVLI

YRNDRRPSGIPDRFSGSKSDTSATLGITGLQTGDEADYYCGTWDNSLSG

WVFG
GGTKLTVL

Nucleic Acid Sequence Encoding the 5.15.C1 Heavy Chain Variable Region (SEQ ID NO: 180)

Protein Sequence Defining the 5.15.C1 Heavy Chain Variable Region (SEQ ID NO: 181)

QVQLVQSGAEVKRPGASVKVSCETSGYSFTTDLNWVRQAAGQGLEWMGW

MNPNTGDT
SYAQRFQGRVTMIRDVSISTAYLELTGLTFDDTAVYFCARS

NSAPVSTLLPADAFDVW
GQGTMVTVSS

Nucleic Acid Sequence Encoding the 5.15.C1 Kappa Chain Variable Region (SEQ ID NO: 182)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTATAGGAG

ACACAGTCACCATCACTTGCCGGGCAAGTCAGATCATTAACAGCTATTT

AAATTGGTATCAGCAAAAACCAGGGGAAGCCCCTAAACTCCTGATCTAT

GCTGTATCC
AATTTGCACCGTGGGGTCCCCTCAAGGTTCAGTGGCAGTG

GGTCTGCGGCAGATTTCACTCTCACTATCAGTGGTCTGCAACCTGAAGA

TTTTGCAACTTACTAC custom-character

GGCCAAGGGACACGACTGGACATTAAAC

Protein Sequence Defining the 5.15.C1 Kappa Chain Variable Region (SEQ ID NO: 183)

DIQMTQSPSSLSASIGDTVTITCRASQIINSYLNWYQQKPGEAPKLLIY

AVS
NLHRGVPSRFSGSGSAADFTLTISGLQPEDFATYYCQQTYTTVAIT

F
GQGTRLDIK

Nucleic Acid Sequence Encoding the 5.54.E6 Heavy Chain Variable Region (SEQ ID NO: 184)

Protein Sequence Defining the 5.54.E6 Heavy Chain Variable Region (SEQ ID NO: 185)

QVQLVQSGAEVKKPGSSVNVSCKASAGTLSGYTINWLRQAPGRGFEWLG

RIIPLGIGNNANWEARVTLTADKSTDTTYLELRDLRSDDVAIYYCAVEF

YRLATVTTPTLDFW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.54.E6 Lambda Chain Variable Region (SEQ ID NO: 186)

TCCTATGTGCTGACTCAGCCACCCTCGGTGTCCGTGGCCCCAGGAACGA

CGGCCAGGATTACCTGTGAGGGGGACCACATTGGAGCTAAAAGTGTGCA

CTGGTACCAGAGGAAGCCAGGCCAGGCCCCTGTGTTGGTCGTCTATATG

AATAGT
GACCGGCCCTCAGGGATCCCTGAGCGATTGTCTGGCTCCAACT

CTGGGAACACGGCCACCCTGAGTATCAGCAGGGTCGAGGCCGAGGATGA

GGCCGACTATTATTGTCAGGTTTGGGATAGTTTTCGCGATCATCAGGTA

TTC
GGCGGAGGGACCAAGTTGACCGTCCTGA

Protein Sequence Defining the 5.54.E6 Lambda Chain Variable Region (SEQ ID NO: 187)

SYVLTQPPSVSVAPGTTARITCEGDHIGAKSVHWYQRKPGQAPVLVVYM

NS
DRPSGIPERLSGSNSGNTATLSISRVEAEDEADYYCQVWDSFRDHQV

F
GGGTKLTVL

Nucleic Acid Sequence Encoding the 5.55.D2 Heavy Chain Variable Region (SEQ ID NO: 188)

CAGGTCACCTTGAAGGAGTCTGGTCCTGCTATAGTGAAACCCACACAG

ACCCTCACGCTGACCTGCACCTTCTCTGGGTTCTCACTCCGAACTAG

TGGAGTGGGT
GTGGGCTGGATCCGTCAGCCCCCAGGAAAGGCCCTT

GAGTGGCTTGCACTCATTTACTGGGATGATGATAAGCGCTACAACC

CATCTCTGAAGACCAGACTCACCATCACCAAGGACTCCTCCAGAAACC

AGGTGTTCCTCACAATGACCAACATGGACCCTGTGGACACAGCCACAT

ACTTCTGTGCACACCGACAACATATTACAAACAGTTTTGGATTGGTT

ATTGCGAATGATGCTTTTGACATTTGG
GGCCAAGGGACAATGGTCA

CCGTCTCGAGTG

Protein Sequence Defining the 5.55.D2 Heavy Chain Variable Region (SEQ ID NO: 189)

QVTLKESGPAIVKPTQTLTLTCTFSGFSLRTSGVGVGWIRQPPGKA

LEWLALIYWDDDKRYNPSLKTRLTITKDSSRNQVFLTMTNMDPVDT

ATYFCARQITNSFGLVIANDAFDIWGQGTMVTVSS

Nucleic Acid Sequence Encoding the 5.55.D2 Lambda Chain Variable Region (SEQ ID NO: 190)

CAGTCTGCCCTGACTCAGCCTCCGTCCGCGTCCGGGTCTCCTGGACAG

TCAGTCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTCGTTA

TAATTAT
GTCGCCTGGTATCAACAACACCCAGGCAGAGCCCCCAGA

CTCATAATTTATGGGGTCACTAAGCGGCCCTCAGGGGTCCCTGATC

GCTTCTCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCGTCTCTG

GGCTCCAGGCTGAAGATGAGGCTGATTATTATTGCAGTTCATATGC

AGGCAGCAACTTTTTGGAGGTGTTC
GGCGGAGGGACCAAGCTGACC

GTCCTAG

Protein Sequence Defining the 5.55.D2 Lambda Chain Variable Region (SEQ ID NO: 191)

QSALTQPPSASGSPGQSVTISCTGTSSDVGRYNYVAWYQQHPGRAP

RLIIYGVTKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCS

SYAGSNFLEVF
GGGTKLTVL

Nucleic Acid Sequence Encoding the 22.14.A1 Heavy Chain Variable Region (SEQ ID NO: 192)

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCC

TCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTA

TGCA
ATCAACTGGGTGCGACAGGCCCCTGGACAAGGTCTTGAGTGG

ATGGGAGGGATCATCCCTATGTTTGATACAGCAATCTACGCACAGA

TGTTCCAGGGCAGAGTCACCATCACCGCGGACGAATCCACGAGCACAG

CCTACATGGAGCTGAGCAGCCTGAGATCTGACGACACGGCCGTATATT

ACTGTGCGAGAGATCGAAACGATTATTATGACAGTAGTGGTTATTCA

GGCGCCTTTGACCAGTGG
GGCCAGGGAACCCTGGTCACCGTCTCGA

GTG

Protein Sequence Defining the 22.14.A1 Heavy Chain Variable Region (SEQ ID NO: 193)

QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAINWVRQAPGQGLE

WMGGIIPMFDTAIYAQMFQGRVTITAPESTSTAYMELSSLRSDDTA

VYYCARDRNDYYDSSGYSGAFDQWGQGTLVTVSS

Nucleic Acid Sequence Encoding the 22.14.A1 Kappa Chain Variable Region (SEQ ID NO: 194)

GAAATTGTGTTGACGCAGTCTCCAGGCGCCCTGTCTTTGTCTCCAGG

GGAAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGC

AGCTAC
TTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGC

TCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAG

GTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACAATCAGCAG

ACTGGAGCCTGAGGATTTTGCAGTGTATTACTGTCAGCAGTATGGT

AGCTCACCTCGCACTTTT
GGCCAGGGGACCAAGCTGGAGATCAAAC

Protein Sequence Defining the 22.14.A1 Kappa Chain Variable Region (SEQ ID NO: 195)

EIVLTQSPGALSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPR

LLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYY

CQQYGSSPRTF
GQGTKLEIK

Nucleic Acid Sequence Encoding the 26.53.B4 Heavy Chain Variable Region (SEQ ID NO: 196)

GAGGTGCAGCTGGTGGAGTCCGGGGGAGGCTTGGTCCAGCCTGGGGGG

TCCCTGAAACTCTCCTGTGCAGCCTCTGGGTTCAGCTTCAGTGGCT

CTGCT
GTGGAATGGGTCCGCCAGGCTTCCGGGAGAGGGCTGGAGTG

GATTGGCCATATAAGAACCAAGACCAAAAATTACGCGACAGCGTAT

GCTGCGTCGGTGCAAGGCAGGTTCACCATCTTCAGAGATGATTCAAGG

AACACGGCGTATCTGCAGATGAACAGTCTTAAAACCGAGGACACGGCCG

TGTATTATTGTTCCAGACACATCGAATTTAGCAGTTCGTCCGGGCCC

CAGATG
GGCCAGGGAACCCTGGTCACCGTCTCGAGTG

Protein Sequence Defining the 26.53.B4 Heavy Chain Variable Region (SEQ ID NO: 197)

EVQLVESGGGLVQPGGSLKLSCAASGFSFSGSAVEWVRQASGRGLE

WIGIRTKTKNYATAYAASVQGRFTIFRDDSRNTAYLQMNSLKTEDT

AVYYCSRIEFSSSSGPQMGQGTLVTVSS

Nucleic Acid Sequence Encoding the 26.53.B4 Kappa Chain Variable Region (SEQ ID NO: 198)

Protein Sequence Defining the 26.53.B4 Kappa Chain Variable Region (SEQ ID NO: 199)

DIQMTQSPSTLSASVGDTVTITCQASQNIITWLAWYQQKPGKAPNI

LIYKASGLESGVPPRFSGSGSGTEFTLTISSLQPDDVATYYCLQ

YKTEPWTF
GLGTKVEIR

Nucleic Acid Sequence Encoding the 5.63.E2 Heavy Chain Variable Region (SEQ ID NO: 200)

GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGCCCAGCCGGGGGAG

TCCCTGAGACTCTCCTGTGCAGCCTCCGGATTCACCTTTAGTGCCT

ATTGG
ATGAGCTGGGTCCGCCAGACTCCAGGGAAGGGGCTGGAGTG

GGTGGCCAACATTAACCAGGGTGGAGATAAGACAGACTATTTGGAC

TCTGTGAAGGGCCGATTCACCGTCTCCAGAGACAATGCCAAGAACTTA

GTGTTTCTGCAAATGGCCAGCCTGAGAGCCGACGACACGGCCGTGTAT

TACTGTGGGAGAGGTACAAACCAAGACTACTGGGGCCAGGGAACCC

TGGTCACCGTCTCGAGTG

Protein Sequence Defining the 5.63.E2 Heavy Chain Variable Region (SEQ ID NO: 201)

EVQLVESGGGLAQPGESLRLSCAASGFTFSAYWMSWVRQTPGKGLE

WVANINQGGDKTDYLDSVKGRFTVSRDNAKNLVFLQMASLRADDTA

VYYCGRGTNQDYWGQGTLVTVSS

Nucleic Acid Sequence Encoding the 5.63.E2 Lambda Chain Variable Region (SEQ ID NO: 202)

CAGTCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAG

AGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAATATCGGAAGTA

ATAAT
GTATACTGGTACCAACAGGTCCCAGGAACGGCCCCCAAATT

TCTCATCTATCCGAATAGTGAGCGGCCCTCAGGGGTCCCTGACCGA

TTCTCTGCCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGA

CTCCGGTCCGAGGATGAGGCTACTTATTACTGTGCAGCATGGGATG

ACAGCCTAAGAACTTATGTCTTC
GCATCTGGGACCAAGGTCAC

Protein Sequence Defining the 5.63.E2 Lambda Chain Variable Region (SEQ ID NO: 203)

QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNNVYWYQQVPGTAPKFL

IYPNSERPSGVPDRFSASKSGTSASLAISGLRSEDEATYYCAAWDDSL

RTYVF
ASGTKVTVL

Nucleic Acid Sequence Encoding the 5.64.G4 Heavy Chain Variable Region (SEQ ID NO: 204)

CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGG

TCCCTGAGACTCTCCTGTGCAGCCTCCGGATTCACCCTCAGGAGTTAT

GGC
ATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGCCTGGAGTGGGTG

GCAGTTATATCATATGATGGAAGTAAGACATATTATAGAGACTCCGTG

AAGGGCCGATTCACCATCTCCAGAGACAATTCTAAGAACACACTGTAT

TTGCAAATGAACAGCCTGCGAGTTGAGGACACGGCTGTATATTATTGT

GCGAAAGAGGATAATTTGGGATCTGATGTTTTTGATAGATGG
GGCCAA

GGGACAATGGTCACCGTCTCGAGTG

Protein Sequence Defining the 5.64.G4 Heavy Chain Variable Region (SEQ ID NO: 205)

QVQLVESGGGVVQPGRSLRLSCAASGFTLRSYGMHWVRQAPGKGLEWV

AVISYDGSKTYYRDSVKGRFTISRDNSKNTLYLQMNSLRVEDTAVYYC

AKEDNLGSDVFDRW
GQGTMVTVSS

Nucleic Acid Sequence Encoding the 5.64.G4 Kappa Chain Variable Region (SEQ ID NO: 206)

Protein Sequence Defining the 5.64.G4 Chain Variable Region (SEQ ID NO: 207)

DIVMTQSPSTLSASVGDRVTITCRASQSASQWLAWYQQKPGKAPNLLIY

KAS
NLHSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNIYPWTF

GQGTKVEVR

Nucleic Acid Sequence Encoding the 43.52.A11 Heavy Chain Variable Region (SEQ ID NO: 208)

CAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGGAGCCAGGGTCC

TCGGTGAGGGTCTCCTGCAAGGCTTCTGGACGCATCTTCCGGAATTAT

GCT
GTCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGGTG

GGCCGGTTCATCCCTTCGGAAGGAATAACAAACTACATTCCGACATTC

CGGGACAGACTCACCTTTACTGCGGACAAGTCCACGAACACAGCCTTC

ATTGACCTGACTAACCTGAAATATGAGGACACGGCCATATATTACTGT

GTGGGTGGCAGGCCAGGCGCTTTCGTCCCCTTTGACTCCTGG
GGCCAG

GGAACCCTGGTCACCGTCTCGAGTG

Protein Sequence Defining the 43.52.A11 Heavy Chain Variable Region (SEQ ID NO: 209)

QVQLVQSGAEVKEPGSSVRVSCKASGRIFRNYAVSWVRQAPGQGLEWV

GRFIPSEGITNYIPTFRDRLTFTADKSTNTAFIDLTNLKYEDTAIYYC

VGGRPGAFVPFDSW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 43.52.A11 Kappa Chain Variable Region (SEQ ID NO: 210)

Protein Sequence Defining the 43.52.A11 Chain Variable Region (SEQ ID NO: 211)

EIVMTQSPATLSVSPGERATLSCRASQSVRGNLAWYQQKPGQAPRLLM

YDASTRATSFPARFSGSGSGTEFTLTISSVQSEDFALYYCQQYNDWPR

TF
GQGTKVEIK

Nucleic Acid Sequence Encoding the 43.52.E12 Heavy Chain Variable Region (SEQ ID NO: 212)

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCC

TCGGTGAGGGTCTCCTGCAGGGTTTCTGGAGGCAGTTTCTCCAGTTAT

GAC
GTACACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGGTG

GGAAGGAGCGTCTCACGTGCTGACAGCTCAAGTCACACACGGGAGTTC

GGGGACAGAGTCACGATTATCGCGGACAAATCCACGAGTACAGTTTAT

TTGACACTGACCAGTCTGACCTCTGACGACACGGCCATCTATTACTGT

GCGGCAGGGGATTGTAGTGATGGCGGGTGCTTCCGCACACCCCTGCAC

ATCTGG
GGCCAGGGCACCCTGGTCACCGTCTCGAGTG

Protein Sequence Defining the 43.52.E12 Heavy Chain Variable Region (SEQ ID NO: 213)

QVQLVQSGAEVKKPGSSVRVSCRVSGGSFSSYDVHWVRQAPGQGLEWV

GRSVSRADSSSHTREFGDRVTIIADKSTSTVYLTLTSLTSDDTAIYYC

AAGDCSDGGCFRTPLHIW
GQGTLVTVSS

Nucleic Acid Sequence Encoding the 43.52.E12 Kappa Chain Variable Region (SEQ ID NO: 214)

Protein Sequence Defining the 43.52.E12 Kappa Chain Variable Region (SEQ ID NO: 215)

EIVMTQSPATLSLSPGERATLSCRASQSLRTNLAWYQQRPGQAPRLLI

SGASTRATGIPARFSGSGSGTEFTLTIRSLQPEDFAVYYCQQYHDWPR

TF
GQGTKVDFK

Nucleic Acid Sequence Encoding the 43.62.E2 Heavy Chain Variable Region (SEQ ID NO: 216)

GAGGTGCAGCTGGTGCAGTCTGGGGCAGAAGTGAAAAAGGCCGGGGAG

TCTCTGAGGATCTCCTGTAAGGGTTCTGGATACAACTTTAATAGCTAT

TGG
ATTGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATG

GCAATCATCTATCCTGCTGACTCTGACAGGAGATATGGCCCGTCCTTC

CAAGGCCAGGTCACCATCTCAGTCGACAAGTCTATTAACACCGCGTAC

TTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTATTGT

GCCAGACTCCTCAGAGTTAGTACTGGTTGGGAAGATGCTTTTGATCTG

TGG
GGCCAAGGGACAATGGTCACCGTCTCGAGTG

Protein Sequence Defining the 43.62.E2 Heavy Chain Variable Region (SEQ ID NO: 217)

EVQLVQSGAEVKKAGESLRISCKGSGYNFNSYWIGWVRQMPGKGLEWM

AIIYPADSDRRYGPSFQGQVTISVDKSINTAYLQWSSLKASDTAMYYC

ARLLRVSTGWEDAFDLW
GQGTMVTVSS

Nucleic Acid Sequence Encoding the 43.62.E2 Kappa Chain Variable Region (SEQ ID NO: 218)

GACATCGTGATGACCCAGTCTCCAGACTCCCTGGTTGTGTCTCTGGG

CGAGAGGGCCACCATCAAGTGCCAGTCCAGCCAGAGTGTTTTGTACA

GCTCCACCAATAAGAACTAT
TTAGCCTGGTACCAGCAGAAATCGGGA

CAGCCACCTAAGCTACTCATTTACTGGGCCTCCACCCGGGAATCCGG

GGTCCCTGACCGATTCATTGGTAGCGGCTCTAGGACAGATTTCACTC

TCACCATCAGCGACCTGCAGCCTGAGGATGCGGCAGTTTATTACTGT

CAGCAGTATTATAGTGATTATCTCACTTTC
GGCGGAGGGACCAAGGT

GGAGATCAAAC

Protein Sequence Defining the 43.62.E2 Kappa Chain Variable Region (SEQ ID NO: 219)

DIVMTQSPDSLVVSLGERATIKCQSSQSVLYSSTNKNYLAWYQQKSG

QPPKLLIYWASTRESGVPDRFIGSGSRTDFTLTISDLQPEDAAVYYCQQ

YYSDYLTF
GGGTKVEIK

Table 2 is a concordance table showing the SEQ ID NO. of the heavy chain and light chain variable region amino acid sequences as a fully human cognate pairs for each anti-S. aureus antibody described herein.

TABLE 2

Heavy Chain
Light Chain

Variable Region
Variable Region

Antibody
(SEQ ID NO:)
(SEQ ID NO:)

1.62.B9
2
4

5.11.H10
11
13

5.27.A11
20
22

5.6.H2
29
31

5.6.H9
38
40

5.17.F8
47
49

5.19.F12
56
58

5.23.C9
65
67

5.23.C12
74
76

8.51.G11
83
85

9.51.H9
92
94

18.43.D8
101
103

22.22.E7
110
112

8.51.G10
149
151

5.24A.A7
153
155

5.24A.F3
157
159

5.8B.H4
161
163

26.51.E1
165
167

22.21.A7
169
171

22.18A.E9
173
175

5.52.H10
177
179

5.15.C1
181
183

5.54.E6
185
187

5.55.D2
189
191

22.14.A1
193
195

26.53.B4
197
199

5.63.E2
201
203

5.64.G4
205
207

43.52.A11
209
211

43.52.E12
213
215

43.62.E2
217
219

Table 3 summarizes the heavy chain and light chain CDR sequences (IMGT definition) of the disclosed S. aureus antibodies.

TABLE 3

Heavy Chain
Light Chain

Antibody
CDR1
CDR2
CDR3
CDR1
CDR2
CDR3

1.62.B9
GFTFSNAW
IKSKTDGGTT
CRTGGYW
TGAVTSGHY
DTS
CLVSDSGARIF

(SEQ ID NO: 5)
(SEQ ID NO: 6)
(SEQ ID NO: 7)
(SEQ ID NO: 8)

(SEQ ID NO: 9)

5.11.H10
GYTFTING
ISTSNGQT
CARNPYGNSRRFFDYW
QTITNY
GVS
CQQSYRAPQTF

(SEQ ID NO: 14)
(SEQ ID NO: 15)
(SEQ ID NO: 16)
(SEQ ID NO: 17)

(SEQ ID NO: 18)

5.27.A11
GFAFSSHE
IGLAGDT
CVKEGAHWEFDSW
SSNLGASLD
ANN
CQSYDGSLRVF

(SEQ ID NO: 23)
(SEQ ID NO: 24)
(SEQ ID NO: 25)
(SEQ ID NO: 26)

(SEQ ID NO: 27)

5.6.H2
GFTFSDYY
ISYISSSGRTI
CARDGGYCGSANCLHDAFDIW
QSISSW
KAS
CQQYNSYSTF

(SEQ ID NO: 32)
(SEQ ID NO: 33)
(SEQ ID NO: 34)
(SEQ ID NO: 35)

(SEQ ID NO: 36)

5.6.H9
GFSLSTSGEG
IYWDDDK
CVHRGMNRVFGVVYNSGWFDPW
QSVRSSQ
DAS
CQQYDTSPWTF

(SEQ ID NO: 41)
(SEQ ID NO: 42)
(SEQ ID NO: 43)
(SEQ ID NO: 44)

(SEQ ID NO: 45)

5.17.F8
GTSFSDYY
INQSGHT
CARFPWVGPEGFDHW
QTIGNS
YGS
CLQSGGFPWTF

(SEQ ID NO: 50)
(SEQ ID NO: 51)
(SEQ ID NO: 52)
(SEQ ID NO: 53)

(SEQ ID NO: 54)

5.19.F12
GSSLPYLS
FDPEDGET
CATSLIRNGLYEAFEHW
DDIKKN
DAS
CQQYDNVPLSF

(SEQ ID NO: 59)
(SEQ ID NO: 60)
(SEQ ID NO: 61)
(SEQ ID NO: 62)

(SEQ ID NO: 63)

5.23.C9
GGNFKNYI
INPKVGNE
CATLRVIGNRRLRPVGGIFDIW
QDVSHY
EAS
CQHDAELPPSF

(SEQ ID NO: 68)
(SEQ ID NO: 69)
(SEQ ID NO: 70)
(SEQ ID NO: 71)

(SEQ ID NO: 72)

5.23.C12
GHSFTAYG
ISTNNGNT
CARNPYGNSRRFLDYW
QNISPY
GTT
CQQSYRAPQTF

(SEQ ID NO: 77)
(SEQ ID NO: 78)
(SEQ ID NO: 79)
(SEQ ID NO: 80)

(SEQ ID NO: 81)

8.51.G11
GFSFTSSGEG
IYWDGDK
CVHLTRPSFWSPYYLFDLW
QYISTYL
GAS
CQQSSTLWSF

(SEQ ID NO: 86)
(SEQ ID NO: 87)
(SEQ ID NO: 88)
(SEQ ID NO: 89)

(SEQ ID NO: 90)

9.51.H9
NYTFTSFG
ISPYNGNT
CARTNWGNWYLDLW
QTILFGSNNKNY
WAS
CQQYFSNPYTF

(SEQ ID NO: 95)
(SEQ ID NO: 96)
(SEQ ID NO: 97)
(SEQ ID NO: 98)

(SEQ ID NO: 99)

18.43.D8
GYIFVDYA
LQSASGKT
CARGSISHYAPFDYW
QNILYTSNNKSF
WAS
CQQYFSTPYTF

(SEQ ID NO: 104)
(SEQ ID NO: 105)
(SEQ ID NO: 106)
(SEQ ID NO: 107)

(SEQ ID NO: 108)

22.22.E7
GAYITNDY
LYTSGST
CARDECSGGGCFHENW
QSISSSY
GAS
CQQYDRSPLTF

(SEQ ID NO: 113)
(SEQ ID NO: 114)
(SEQ ID NO: 115)
(SEQ ID NO: 116)

(SEQ ID NO: 117)

8.51.G10
GFSFTSSGEA
IYWDDDP
CAHLRRPSLWSPYYLFDCW
QSISS
GAS
CQQSYKMWSF

(SEQ ID NO: 220)
(SEQ ID NO: 221)
(SEQ ID NO: 222)
(SEQ ID NO: 223)

(SEQ ID NO: 224)

5.24A.A7
GYTFTNFG
INTHNGNT
CARDFFRAAAGTAGDYW
HSGTNNY
GAS
CQQSYKMWSF

(SEQ ID NO: 225)
(SEQ ID NO: 226)
(SEQ ID NO: 227)
(SEQ ID NO: 228)

(SEQ ID NO: 229)

5.24A.F3
GGSISNDY
VYYSGRT
CARTTRLSFDWLVHYYGMDVW
QPIGSY
AAS
CQQSYNNPLFTF

(SEQ ID NO: 230)
(SEQ ID NO: 231)
(SEQ ID NO: 232)
(SEQ ID NO: 233)

(SEQ ID NO: 234)

5.8B.H4
GFIFDDYG
ITWDGVNT
CARARYYQGTGLRSYLDEW
QGIDNW
AAS
CQQAKNFPRGGFTF

(SEQ ID NO: 235)
(SEQ ID NO: 236)
(SEQ ID NO: 237)
(SEQ ID NO: 238)

(SEQ ID NO: 239)

26.51.E1
GFTFSKFA
IASDGYNK
CAYGHLSFWFDPW
QDIGNG
AAS
CLQHNFYPRTF

(SEQ ID NO: 240)
(SEQ ID NO: 241)
(SEQ ID NO: 242)
(SEQ ID NO: 243)

(SEQ ID NO: 244)

22.21.A7
GYTFTDYY
INPYSGGT
CARDFFRAAAGTAGDYW
QSALYSPSSKTY
WAS
CQYYYGTVTF(SEQ

(SEQ ID NO: 245)
(SEQ ID NO: 246)
(SEQ ID NO: 247)
(SEQ ID NO: 248)

ID NO: 249)

22.18A.E9
GGSINSYY
MYPGGTS
CARDPTYHHGTSGYVGTFDLW
PSVRNN
GAS
CQQYNSWPPYTF

(SEQ ID NO: 250)
(SEQ ID NO: 251)
(SEQ ID NO: 252)
(SEQ ID NO: 253)

(SEQ ID NO: 254)

5.52.H10
GFTFSMFT
ISGSSSLV
CVRGDSRDYW
TSNIGNNH
RND
CGTWDNSLSGWVF

(SEQ ID NO: 255)
(SEQ ID NO: 256)
(SEQ ID NO: 257)
(SEQ ID NO: 258)

(SEQ ID NO: 259)

5.15.C1
GYSFTTD
MNPNTGDT
CARSNSAPVSTLLPADAFDVW
QIINSY
AVS
CQQTYTTVAITF

(SEQ ID NO: 260)
(SEQ ID NO: 261)
(SEQ ID NO: 262)
(SEQ ID NO: 263)

(SEQ ID NO: 264)

5.54.E6
AGTLSGYT
IIPLGIG
CAVEFYRLATVTTPTLDFW
HIGAKS
MNS
CQVWDSFRDHQVF

(SEQ ID NO: 265)
(SEQ ID NO: 266)
(SEQ ID NO: 267)
(SEQ ID NO: 268)

(SEQ ID NO: 269)

5.55.D2
GFSLRTSGVG
IYWDDDK
CARQITNSFGLVIANDAFDIW
SSDVGRYNY
GVT
CSSYAGSNFLEVF

(SEQ ID NO: 270)
(SEQ ID NO: 271)
(SEQ ID NO: 272)
(SEQ ID NO: 273)

(SEQ ID NO: 274)

22.14.A1
GGTFSSYA
IIPMFDTA
CARDRNDYYDSSGYSGAFDQW
QSVSSSY
GAS
CQQYGSSPRTF

(SEQ ID NO: 275)
(SEQ ID NO: 276)
(SEQ ID NO: 277)
(SEQ ID NO: 278)

(SEQ ID NO: 279)

26.53.B4
GFSFSGSA
IRTKTKNYAT
CSRIEFSSSSGPQM
QNIITW
KAS
CLQYKTEPWTF

(SEQ ID NO: 280)
(SEQ ID NO: 281)
(SEQ ID NO: 282)
(SEQ ID NO: 283)

(SEQ ID NO: 284)

5.63.E2
GFTFSAYW
INQGGDKT
CGRGTNQDYW
SSNIGSNN
PNS
CAAWDDSLRTYVF

(SEQ ID NO: 285)
(SEQ ID NO: 286)
(SEQ ID NO: 287)
(SEQ ID NO: 288)

(SEQ ID NO: 289)

5.64.G4.
GFTLRSYG
ISYDGSKT
CAKEDNLGSDVFDRW
QSASQW
KAS
CQQYNIYPWTF

(SEQ ID NO: 290)
(SEQ ID NO: 291)
(SEQ ID NO: 292)
(SEQ ID NO: 293)

(SEQ ID NO: 294)

43.52.A11
GRIFRNYA
FIPSEGIT
CVGGRPGAFVPFDSW
QSVRGN
DAS
CQQYNDWPRTF

(SEQ ID NO: 295)
(SEQ ID NO: 296)
(SEQ ID NO: 297)
(SEQ ID NO: 298)

(SEQ ID NO: 299)

43.52.E12
GGSFSSYD
SVSRADSS
CAAGDCSDGGCFRTPLHIW
QSLRTN
GAS
CQQYHDWPRTF

(SEQ ID NO: 300)
(SEQ ID NO: 301)
(SEQ ID NO: 302)
(SEQ ID NO: 303)

(SEQ ID NO: 304)

43.62.E2
GYNFNSYW
IYPADSDR
CARLLRVSTGWEDAFDLW
QSVLYSSTNKNY
WAS
CQQYYSDYLTF

(SEQ ID NO: 305)
(SEQ ID NO: 306)
(SEQ ID NO: 307)
(SEQ ID NO: 308)

(SEQ ID NO: 309)

To create complete heavy and/or light chain antibody sequences, each variable sequence above can be combined with a constant region. Human constant regions for heavy chain, kappa chain, and lambda chain are known in the art. For example, a complete heavy chain comprises a heavy variable sequence followed by a human heavy chain constant sequence such as IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgD, or IgE. A complete kappa chain comprises a kappa variable sequence followed by the human kappa light chain constant sequence, and a complete lambda chain comprises a lambda variable sequence followed by the human lambda light chain constant sequence. Exemplary human heavy chain, kappa chain, and lambda chains are shown below.

Nucleic Acid Sequence Encoding the genomic Human IgG1 Heavy Chain Constant Region (SEQ ID NO: 118)

CCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAG

AGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTA

CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCA

GCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTAC

TCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCA

GACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGG

ACAAGAAAGTTGGTGAGAGGCCAGCACAGGGAGGGAGGGTGTCTGCT

GGAAGCAGGCTCAGCGCTCCTGCCTGGACGCATCCCGGCTATGCAGC

CCCAGTCCAGGGCAGCAAGGCAGGCCCCGTCTGCCTCTTCACCCGGA

GCCTCTGCCCGCCCCACTCATGCTCAGGGAGAGGGTCTTCTGGCTTT

TTCCCAGGCTCTGGGCAGGCACAGGCTAGGTGCCCCTAACCCAGGCC

CTGCACACAAAGGGGCAGGTGCTGGGCTCAGACCTGCCAAGAGCCAT

ATCCGGGAGGACCCTGCCCCTGACCTAAGCCCACCCCAAAGGCCAAA

CTCTCCACTCCCTCAGCTCGGACACCTTCTCTCCTCCCAGATTCCAG

TAACTCCCAATCTTCTCTCTGCAGAGCCCAAATCTTGTGACAAAACT

CACACATGCCCACCGTGCCCAGGTAAGCCAGCCCAGGCCTCGCCCTC

CAGCTCAAGGCGGGACAGGTGCCCTAGAGTAGCCTGCATCCAGGGAC

AGGCCCCAGCCGGGTGCTGACACGTCCACCTCCATCTCTTCCTCAGC

ACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAAC

CCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG

GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTA

CGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGG

AGCAGTACAACAGCACGTACCGGGTGGTCAGCGTCCTCACCGTCCTG

CACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAA

CAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAG

GTGGGACCCGTGGGGTGCGAGGGCCACATGGACAGAGGCCGGCTCGG

CCCACCCTCTGCCCTGAGAGTGACCGCTGTACCAACCTCTGTCCTAC

AGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGG

ATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC

TTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCC

GGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCT

CCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAG

CAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAA

CCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Nucleic Acid Sequence Encoding the Human IgG1 Heavy Chain Constant Region cDNA (SEQ ID NO: 119)

Protein Sequence Defining the Human IgG1 Heavy Chain Constant Region (SEQ ID NO: 120)

STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTS

GVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD

KKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEV

TCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL

TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS

DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

Nucleic Acid Sequence Encoding the genomic Human IgG2 Heavy Chain Constant Region (SEQ ID NO: 121)

CCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGG

AGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTA

CTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACCA

GCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTAC

TCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAACTTCGGCACCCA

GACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG

ACAAGACAGTTGGTGAGAGGCCAGCTCAGGGAGGGAGGGTGTCTGCT

GGAAGCCAGGCTCAGCCCTCCTGCCTGGACGCACCCCGGCTGTGCAG

CCCCAGCCCAGGGCAGCAAGGCAGGCCCCATCTGTCTCCTCACCCGG

AGGCCTCTGCCCGCCCCACTCATGCTCAGGGAGAGGGTCTTCTGGCT

TTTTCCACCAGGCTCCAGGCAGGCACAGGCTGGGTGCCCCTACCCCA

GGCCCTTCACACACAGGGGCAGGTGCTTGGCTCAGACCTGCCAAAAG

CCATATCCGGGAGGACCCTGCCCCTGACCTAAGCCGACCCCAAAGGC

CAAACTGTCCACTCCCTCAGCTCGGACACCTTCTCTCCTCCCAGATC

CGAGTAACTCCCAATCTTCTCTCTGCAGAGCGCAAATGTTGTGTCGA

GTGCCCACCGTGCCCAGGTAAGCCAGCCCAGGCCTCGCCCTCCAGCT

CAAGGCGGGACAGGTGCCCTAGAGTAGCCTGCATCCAGGGACAGGCC

CCAGCTGGGTGCTGACACGTCCACCTCCATCTCTTCCTCAGCACCAC

CTGTGGCAGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGAC

ACCCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGA

CGTGAGCCACGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGACG

GCGTGGAGGTGCATAATGCCAAGACAAAGCCACGGGAGGAGCAGTTC

AACAGCACGTTCCGTGTGGTCAGCGTCCTCACCGTTGTGCACCAGGA

CTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCC

TCCCAGCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGTGGGACC

CGCGGGGTATGAGGGCCACATGGACAGAGGCCGGCTCGGCCCACCCT

CTGCCCTGGGAGTGACCGCTGTGCCAACCTCTGTCCCTACAGGGCAG

CCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGAT

GACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACC

CCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAAC

AACTACAAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTTCTT

CCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGA

ACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC

ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Nucleic Acid Sequence Encoding the Human IgG2 Heavy Chain Constant Region cDNA (SEQ ID NO: 122)

Protein Sequence Defining the Human IgG2 Heavy Chain Constant Region (SEQ ID NO: 123)

STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTS

GVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVD

KTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVV

VDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVH

QDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREE

MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

Nucleic Acid Sequence Encoding the Human Kappa Light Chain Constant Region (SEQ ID NO: 124)

GAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAG

CAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTT

CTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC

AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGAC

AGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTA

CGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA

GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT

Protein Sequence Defining the Human Kappa Light Chain Constant Region (SEQ ID NO: 125)

RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS

GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV

TKSFNRGEC

Nucleic Acid Sequence Encoding the Human Lambda Light Chain Constant Region (SEQ ID NO: 126)

GTCAGCCCAAGGCCAACCCCACTGTCACTCTGTTCCCGCCCTCCTCTGA

GGAGCTCCAAGCCAACAAGGCCACACTAGTGTGTCTGATCAGTGACTTC

TACCCGGGAGCTGTGACAGTGGCCTGGAAGGCAGATGGCAGCCCCGTCA

AGGCGGGAGTGGAGACCACCAAACCCTCCAAACAGAGCAACAACAAGTA

CGCGGCCAGCAGCTACCTGAGCCTGACGCCCGAGCAGTGGAAGTCCCAC

AGAAGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGA

CAGTGGCCCCTACAGAATGTTCA

Protein Sequence Defining the Human Lambda Light Chain Constant Region (SEQ ID NO: 127)

GQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPV

KAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEK

TVAPTECS

It is appreciated, however, that the variable region sequences described herein can be ligated to each of a number of other constant region sequences known to those skilled in the art to produce active full length immunoglobulin heavy and light chains.

The following sequences represent the actual or contemplated full length immunoglobulin heavy and light chain sequences (i.e., containing both the variable and constant regions sequences) for the anti-S. aureus antibodies described herein. The immunoglobulin heavy chain and light chain variable regions are shown as uppercase letters and the human IgG1, IgG2, kappa and lambda constant regions are shown in bold uppercase letters in the full length heavy and light chain sequences. CDR sequences are underlined.

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 1.62.B9 (SEQ ID NO: 128)

GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTAAAGCCTGGGGG

GTCCCTTAGACTCTCCTGTGCAGCCTCTGGATTCACTTTCAGTAACG

CCTGGATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGG

GTTGGCCGTATTAAGAGCAAAACTGATGGTGGGACAACAGACTACGC

TGCACCCGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCAATAA

ACACACTGTATCTGCAAATGAACAGCCTGAAAACCGAGGACACAGCC

GTGTATTATTGTAGGACGGGGGGCTACTGGGGCCAGGGAACCCTGGT

CACCGTCTCGAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGG

CGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGC

CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTC

AGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACAGT

CCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGC

AACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACAAGCCCAG

CAACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGTCGAGT

GCCCACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTCCTC

TTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGA

GGTCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCC

AGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACA

AAGCCACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGT

CCTCACCGTTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGT

GCAAGGTCTCCAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCATC

TCCAAAACCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCC

CCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCC

TGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGC

AATGGGCAGCCGGAGAACAACTACAAGACCACACCTCCCATGCTGGA

CTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGA

GCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG

GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGG

TAAATGA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 1.62.B9 (SEQ ID NO: 129)

EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMTWVRQAPGKGLEWVG

RIKSKTDGGTTDYAAPVKGRFTISRDDSINTLYLQMNSLKTEDTAVYYC

RTGGYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF

PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYT

CNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLM

ISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFR

VVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

Nucleic Acid Sequence Encoding the Full Length Lambda Light Chain Sequence of 1.62.B9 (SEQ ID NO: 130)

CAGGCTGTGGTGACTCAGGAGCCCTCACTGACTGTGTCCCCAGGAGGGAC

AGTCACTCTCACCTGTGGCTCCAGCACTGGAGCTGTCACCAGTGGTCATT

ATCCCTACTGGTTCCAGCAGAAGCCTGGCCAAGCCCCCAGGACACTGATT

TATGATACAAGCAAGAAACATTCCTGGACACCTGCCCGGTTCTCAGGCTC

CCTCCTTGGGGGCAAAGCTGCCCTGACCCTTTCGGGTGCGCAGCCTGAGG

ATGAGGCTGAGTATTACTGCTTGGTCTCCGATAGTGGTGCTCGGATCTTC

GGACCTGGGACCAAGGTCACCGTCCTAGGTCAGCCCAAGGCCAACCCCAC

TGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTCCAAGCCAACAAGGCCA

CACTAGTGTGTCTGATCAGTGACTTCTACCCGGGAGCTGTGACAGTGGCC

TGGAAGGCAGATGGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCAAACC

CTCCAAACAGAGCAACAACAAGTACGCGGCCAGCAGCTACCTGAGCCTGA

CGCCCGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGGTCACGCAT

GAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCA

Protein Sequence Defining the Full Length Lambda Light Chain Sequence of 1.62.B9 (SEQ ID NO: 131)

QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYPYWFQQKPGQAPRTLI

YDTSKKHSWTPARFSGSLLGGKAALTLSGAQPEDEAEYYCLVSDSGARIF

GPGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVA

WKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTH

EGSTVEKTVAPTECS

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.11.H10 (SEQ ID NO: 132)

CAGGTTCAGCTGGTGCAGTCTGGACCTGAAATGAAGAAGCCTGGGGCCTC

AGTGAAGGTCTCCTGTCAGGCCTCTGGTTACACCTTTACCATTAATGGAA

TTAGTTGGGTGCGACAGGCCCCTGGACAACGGCCTGAGTGGATGGGGTGG

ATCAGCACTAGTAATGGTCAGACAAACTTTGCACAGAATTTCCAGGGCAG

ACTCACCTTGACCACAGACACATCCACGACCACGGCCTTCATGGAGTTGA

TGAGCCTCACATCTGCCGACACGGCCGTATACTACTGTGCGAGAAATCCA

TACGGCAATTCGCGCAGATTCTTTGACTACTGGGGCCAGGGAACCCTGGT

CACCGTCTCGAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGC

CCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTC

AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCT

GACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCT

ACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAACTTCGGCACCCAG

ACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAA

GACAGTTGAGCGCAAATGTTGTGTCGAGTGCCCACCGTGCCCAGCACCAC

CTGTGGCAGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACC

CTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAG

CCACGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGACGGCGTGGAGG

TGCATAATGCCAAGACAAAGCCACGGGAGGAGCAGTTCAACAGCACGTTC

CGTGTGGTCAGCGTCCTCACCGTTGTGCACCAGGACTGGCTGAACGGCAA

GGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCAGCCCCCATCGAGA

AAACCATCTCCAAAACCAAAGGGCAGCCCCGAGAACCACAGGTGTACACC

CTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTG

CCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCA

ATGGGCAGCCGGAGAACAACTACAAGACCACACCTCCCATGCTGGACTCC

GACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTG

GCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACA

ACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.11.H10 (SEQ ID NO: 133)

QVQLVQSGPEMKKPGASVKVSCQASGYTFTINGISWVRQAPGQRPEWMGW

ISTSNGQTNFAQNFQGRLTLTTDTSTTTAFMELMSLTSADTAVYYCARNP

YGNSRRFFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLV

KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ

TYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTF

RVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDS

DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 5.11.H10 (SEQ ID NO: 134)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCCTCTGTTGGCGA

CAGAGTCATCATCACTTGCCGGACAAGTCAGACCATCACCAATTACATAA

ATTGGTATCAGCAAAAACCAGGGAAAGCCCCGCAGCTCCTGATCTATGGT

GTATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCGGTGGATC

TGGGACAGAATTCACTCTCACCATCAGCAGTCTGCAACCTGAAGACTTTG

CAACTTATTACTGTCAACAGAGTTATAGGGCCCCTCAAACATTCGGCCAA

GGGACCAAGCTGGAAATCAAACGAACTGTGGCTGCACCATCTGTCTTCAT

CTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGT

GCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTG

GATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGA

CAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAG

CAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGC

CTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 5.11.H10 (SEQ ID NO: 135)

DIQMTQSPSSLSASVGDRVIITCRTSQTITNYINWYQQKPGKAPQLLIYG

VSSLQSGVPSRFSGGGSGTEFTLTISSLQPEDFATYYCQQSYRAPQTFGQ

GTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV

DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG

LSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.27.A11 (SEQ ID NO: 136)

GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTGCAGCCGGGGGGGTC

TCTGAGACTCTCTTGTGCAGCCTCTGGTTTCGCCTTCAGCAGCCACGAGA

TGCACTGGGTTCGTCAAGGGATAGGACACAGTTTGGAGTGGGTCTCAGCT

ATTGGCCTTGCTGGTGACACATATTATTCAGACTCCGTGAAGGGCCGCTT

CACCATCTCCAGAGAAAACGCCAAGAACACTTTGTATCTTGAAATGAACA

ATTTGAGAGTCGGCGACACGGCTGTCTATTACTGTGTCAAAGAAGGGGCT

CATTGGGAATTTGACTCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAG

TGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGA

GCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTC

CCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGT

GCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCA

GCGTGGTGACCGTGCCCTCCAGCAACTTCGGCACCCAGACCTACACCTGC

AACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGACAGTTGAGCG

CAAATGTTGTGTCGAGTGCCCACCGTGCCCAGCACCACCTGTGGCAGGAC

CGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCC

CGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACCC

CGAGGTCCAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCA

AGACAAAGCCACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTCAGC

GTCCTCACCGTTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTG

CAAGGTCTCCAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCATCTCCA

AAACCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCC

CGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGG

CTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGG

AGAACAACTACAAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTTC

TTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA

CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGC

AGAAGAGCCTCTCCCTGTCTCCGGGTAAATGA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.27.A11 (SEQ ID NO: 137)

EVQLVESGGGLVQPGGSLRLSCAASGFAFSSHEMHWVRQGIGHSLEWVSA

IGLAGDTYYSDSVKGRFTISRENAKNTLYLEMNNLRVGDTAVYYCVKEGA

HWEFDSWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF

PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTC

NVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMIS

RTPEVTCVVVDVSHEDPEVQPNWYVDGVEVHNAKTKPREEQFNSTFRVVS

VLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSF

FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Lambda Light Chain Sequence of 5.27.A11 (SEQ ID NO: 138)

CAGTCTGTGCTGACGCAGCCGCCCTCAGTGTCTGGGGCCCCTGGACAGAG

GGTCATCATCTCCTGCACTGGGAGCAGCTCCAACCTCGGGGCAAGTCTTG

ATGTACACTGGTACCAGCGCCTTCCAGGGACAGGCCCCCGACTCCTCATC

TATGCTAACAACAATCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTC

CAAGTCTGGCACCTCAGCCTCCCTGGCCATCACCGGGCTCCAGGCTGAAG

ATGAGGGTGATTATTACTGCCAGTCCTATGACGGCAGCCTGAGGGTGTTC

GGCGGAGGGACCAGGCTGACCGTCCTAGGTCAGCCCAAGGCTGCCCCCTC

GGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAGGCCA

CACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC

TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACC

CTCCAAACAAAGCAACAACAAGTACGCGGCCAGCAGCTACCTGAGCCTGA

CGCCTGAGCAGTGGAAGTCCCACAAAAGCTACAGCTGCCAGGTCACGCAT

GAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATGTTCA

Protein Sequence Defining the Full Length Lambda Light Chain Sequence of 5.27.A11 (SEQ ID NO: 139)

QSVLTQPPSVSGAPGQRVIISCTGSSSNLGASLDVHWYQRLPGTGPRLLI

YANNNRPSGVPDRFSGSKSGTSASLAITGLQAEDEGDYYCQSYDGSLRVF

GGGTRLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVA

WKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTH

EGSTVEKTVAPTECS

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.6.H2 (SEQ ID NO: 140)

CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGTTCAAGCCTGGAGGGTC

CCTGAGACTGTCCTGTGCAGCCTCTGGATTCACCTTCAGTGACTACTACA

TGAGCTGGATCCGGCAGGCTCCAGGGAAGGGGCTGGAGTGGATTTCATAC

ATTAGTAGTAGTGGTAGGACCATAAAGTACGCAGACTCTGTGAAGGGCCG

ATTCACCATCTCCAGGGACAACGCCAAGAACTCACTTTATCTGCAAATGA

ACAGCCTGAGAGCCGAGGACACGGCCGTGTATTATTGTGCGAGAGATGGA

GGATATTGTGGAAGTGCAAACTGCCTTCATGACGCTTTTGATATCTGGGG

CCAAGGGACAATGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCCATCGG

TCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCC

CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTG

GAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTAC

AGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGC

AACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAA

CACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGTCGAGTGCCCAC

CGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTCCTCTTCCCCCCA

AAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGT

GGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCCAGTTCAACTGGTACG

TGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCACGGGAGGAGCAG

TTCAACAGCACGTTCCGTGTGGTCAGCGTCCTCACCGTTGTGCACCAGGA

CTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCC

CAGCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGGCAGCCCCGAGAA

CCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCA

GGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCG

TGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACACCT

CCCATGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGT

GGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGC

ATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCG

GGTAAATGA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.6.H2 (SEQ ID NO: 141)

QVQLVESGGGLFKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWISY

ISSSGRTIKYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDG

GYCGSANCLHDAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

NFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQ

FNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP

PMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 5.6.H2 (SEQ ID NO: 142)

GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGA

CAGAGTCACCATCACTTGCCGGGCCAGTCAGAGTATTAGTAGCTGGTTGG

CCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAG

GCGTCTAGTTTAGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATC

TGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTG

CAACTTATTACTGCCAACAGTATAATAGTTATTCGACGTTCGGCCAAGGG

ACCAAGGTGGAAATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTT

CCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCC

TGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGAT

AACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAG

CAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAG

ACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTG

AGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 5.6.H2 (SEQ ID NO: 143)

DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYK

ASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSTFGQG

TKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD

NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL

SSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.6.H9 (SEQ ID NO: 144)

CAGGTCACCTTGAAGGAGTCTGGTCCCACGCTGGTGAAACCCACACAGAC

CCTCACGCTGACGTGCACCTTCTCTGGGTTTTCGCTCAGCACTAGTGGAG

AGGGTGTGGCCTGGATCCGTCAGGCCCCAGGAAAGGCCCTGGAGTGGCTT

GCACTCATTTATTGGGATGATGATAAGCGCTACAACCCATCTCTGAAGAG

CAGGCTCACCATCACCAAGGACAACTCCAGAAACCAAGTGGTCCTTACAA

TGACCAACATGGACCCTGTGGACACAGCCACATATTACTGTGTACACAGG

GGGATGAATAGGGTTTTTGGGGTAGTTTATAATTCGGGCTGGTTCGACCC

CTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCCTCCACCAAGGGCC

CATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACA

GCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGT

GTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTG

TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC

TCCAGCAACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACAAGCC

CAGCAACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGTCGAGT

GCCCACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTCCTCTTC

CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCAC

GTGCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCCAGTTCAACT

GGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCACGGGAG

GAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGTCCTCACCGTTGTGCA

CCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAG

GCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGGCAGCCC

CGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAA

GAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACA

TCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC

ACACCTCCCATGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCT

CACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCG

TGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTG

TCTCCGGGTAAATGA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.6.H9 (SEQ ID NO: 145)

QVTLKESGPTLVKPTQTLTLTCTFSGFSLSTSGEGVAWIRQAPGKALEW

LALIYWDDDKRYNPSLKSRLTITKDNSRNQVVLTMTNMDPVDTATYYCV

HRGMNRVFGVVYNSGWFDPWGQGTLVTVSSASTKGPSVFPLAPCSRSTS

ESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV

VTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQPNWYVDGVEVHNA

KTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTI

SKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN

HYTQKSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 5.6.H9 (SEQ ID NO: 146)

GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGG

AAAGAGCCACCCTCTCCTGTAGGGCCAGTCAGAGCGTTAGAAGCAGCCA

GCTAGCCTGGTACCAGCAGAAGCCTGGCCAGGCTCCCAGCCTCCTCATG

TATGACGCATCTAAGAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCA

GTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA

AGATTTTGTAGTGTATTTCTGTCAGCAGTATGATACATCACCGTGGACG

TTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTGGCTGCACCAT

CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGC

CTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTA

CAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT

GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA

GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG

GAGAGTGT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 5.6.H9

(SEQ ID NO: 147)

EIVLTQSPGTLSLSPGERATLSCRASQSVRSSQLAWYQQKPGQAPSLLM

YDASKRATGIPDRFSGSGSGTDFTLTISRLEPEDFVVYFCQQYDTSPWT

FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV

QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE

VTHQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 8.51.G10 (SEQ ID NO: 310)

CAGATCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAACCCCACACAGA

CCCTCACGCTGACCTGCACCTTTTCTGGGTTCTCATTCACCTCTAGTGG

AGAGGCTGTGGGCTGGATCCGTCAGCCCCCAGGAAAGGCCCTGGAATGG

CTTGCTCACATTTATTGGGATGATGATCCGCGTTATAGTACATCTCTGA

AGAGCAGACTCACCATCACCAAGGACACCTCCAAAAATCAGGTGGTCCT

CTCTATGACCGACATTGACCCTGCGGACACAGGCACATATTACTGTGCA

CACCTGAGACGCCCATCCCTTTGGAGTCCTTATTATCTTTTTGACTGCT

GGGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCC

ATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACA

GCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG

TGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGC

TGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTG

CCCTCCAGCAACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACA

AGCCCAGCAACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGT

CGAGTGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTC

CTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG

AGGTCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCCA

GTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG

CCACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGTCCTCA

CCGTTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGT

CTCCAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAACC

AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGG

AGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT

CTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAG

AACAACTACAAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTTCT

TCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA

CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 8.51.G10 (SEQ ID NO: 311)

QITLKESGPTLVNPTQTLTLTCTFSGFSFTSSGEAVGWIRQPPGKALEW

LAHIYWDDDPRYSTSLKSRLTITKDTSKNQVVLSMTDIDPADTGTYYCA

HLRRPSLWSPYYLFDCWGQGTLVTVSSSTKGPSVFPLAPCSRSTSESTA

ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP

SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP

REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTK

GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 8.51.G10 (SEQ ID NO: 312)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTTGGAG

ACAGAGTCACCATCACTTGCCGGGCAAGTCAGAGTATTAGTAGCTATTT

AAATTGGTATCAACTGAAACCAGGACAAGCCCCTAAGCTCCTGATCTAT

GGTGCATCCAGTTTGGAAAATGGGGTCCCTTCACGGTTCAGTGGCAGTG

GCTCTGGGCCAGATTTCACTCTCACCATTAGCAGTCTGCAACCTGAAGA

TTTTGCAACTTACTACTGTCAACAGAGTTACAAAATGTGGTCATTCGGC

CAAGGGACCAAGGTGGAAATCCAACGAACTGTGGCTGCACCATCTGTCT

TCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGT

TGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGG

AAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAG

AGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCT

GAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC

CATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGT

GT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 8.51.G10 (SEQ ID NO: 313)

DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQLKPGQAPKLLIY

GASSLENGVPSRFSGSGSGPDFTLTISSLQPEDFATYYCQQSYKMWSFG

QGTKVEIQRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW

KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.24A.A7 (SEQ ID NO: 314)

CAGGTTCAGCTGGTGCAGTCTGGAGTTGAGGTGAAGAAGCCTGGGGCCT

CAGTGAAGGTCTCCTGCAAGGCTTCTGGCTACACCTTTACCAACTTTGG

CTTCAGTTGGGTGCGGCAGGCCCCAGGACAAGGGCTTGAGTGGCTGGGA

TGGATCAACACTCATAACGGTAACACAAACTATGCACCGAGATTCCAAG

ACAGAGTCACCCTGACCACAGACACATCCACGACCACAGCCTACATGGA

GCTGAGGAGCCTGAGATCTGAGGACACGGCCGTGTATTATTGTGCGAGA

GATCTTGGGGGAAGTAGTTCCGCCTACTGGGGACAGGGAACCCTGGTCA

CCGTCTCGAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCC

CTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTC

AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTC

TGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACT

CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAACTTCGGCACC

CAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG

ACAAGACAGTTGAGCGCAAATGTTGTGTCGAGTGCCCACCGTGCCCAGC

ACCACCTGTGGCAGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAG

GACACCCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGG

ACGTGAGCCACGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGACGG

CGTGGAGGTGCATAATGCCAAGACAAAGCCACGGGAGGAGCAGTTCAAC

AGCACGTTCCGTGTGGTCAGCGTCCTCACCGTTGTGCACCAGGACTGGC

TGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCAGC

CCCCATCGAGAAAACCATCTCCAAAACCAAAGGGCAGCCCCGAGAACCA

CAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGG

TCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGT

GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACACCT

CCCATGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCG

TGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGAT

GCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCT

CCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.24A.A7 (SEQ ID NO: 315)

QVQLVQSGVEVKKPGASVKVSCKASGYTFTNFGFSWVRQAPGQGLEWLG

WINTHNGNTNYAPRFQDRVTLTTDTSTTTAYMELRSLRSEDTAVYYCAR

DLGGSSSAYWGQGTLVTVSSSTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ

TYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVQPNWYVDGVEVHNAKTKPREEQFNS

TFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ

VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

MLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 5.24A.A7 (SEQ ID NO: 316)

GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGG

AGAGAGCCACCCTCTCTTGCAGGGCCAGTCACAGTGGTACCAACAACTA

CATCGCCTGGTACCAGCAGAAACCTGGCCAGCCTCCCAGGCTCCTCATC

TATGGTGCATCCAGCAGGGCCCCTGGCATCTCAGAGAGGTTCAGCGGCA

GTGGGTCTGGGACAGACTTCACTCTCATCATCAGCAGACTGGAGCCTGA

AGACTTTGGAGTATATTACTGTGAGCAGTATGGGAACTCACCTCTGACG

TTCGGCCAAGGGACCAAGGTGGAAATCAAACGAACTGTGGCTGCACCAT

CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGC

CTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTA

CAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT

GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA

GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG

GAGAGTGT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 5.24A.A7 (SEQ ID NO: 317)

EIVLTQSPGTLSLSPGERATLSCRASHSGTNNYIAWYQQKPGQPPRLLI

YGASSRAPGISERFSGSGSGTDFTLIISRLEPEDFGVYYCEQYGNSPLT

FGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV

QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE

VTHQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.24A.F3 (SEQ ID NO: 318)

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGGAGTCTTCGGACG

TCCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGTAATGACTA

TTGGGCCTGGATCCGGCAGACCCCAGGGAAGGGACTGGAGTGGATTGGG

TCTGTCTATTACAGTGGCAGAACCAGTTTCAGCCCCTCCCTCAAGAGTC

GAGTCACTATGTCAGTGGACACGACCAAGAACCAATTCTTCCTGAACCT

GGGCTCTCTGACCGTTGCGGACACGGCCGTGTATTACTGTGCGAGAACT

ACAAGGTTGTCCTTTGACTGGTTAGTACACTACTATGGAATGGACGTCT

GGGGCCAGGGGACCACGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCC

ATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACA

GCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG

TGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGC

TGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTG

CCCTCCAGCAACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACA

AGCCCAGCAACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGT

CGAGTGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTC

CTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG

AGGTCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCCA

GTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG

CCACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGTCCTCA

CCGTTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGT

CTCCAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAACC

AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGG

AGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT

CTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAG

AACAACTACAAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTTCT

TCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA

CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.24A.F3 (SEQ ID NO: 319)

QVQLQESGPGLVESSDVLSLTCTVSGGSISNDYWAWIRQTPGKGLEWIG

SVYYSGRTSFSPSLKSRVTMSVDTTKNQFFLNLGSLTVADTAVYYCART

TRLSFDWLVHYYGMDVWGQGTTVTVSSSTKGPSVFPLAPCSRSTSESTA

ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP

SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP

REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTK

GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 5.24A.F3 (SEQ ID NO: 320)

GACATCCAGATGACCCAGTCTCCATCGTCCCTGACTGCATCTGTAGGAG

ACAGAGTCACCATTATTTGTCGGGCAAGTCAGCCCATTGGCAGCTATTT

GAATTGGTATCAGCAGAGTCCAGGGAAAGCCCCTAAACTCCTCATCTAT

GCTGCATCCACTTTGCAGAGTGGGGTCCCATCAAGGTTCAGTGGCAGTG

GATCTGGGACAGATTTCACTCTCAACATCAGTGGTCTGCAACCTGAAGA

TTTTGCAACTTACTACTGTCAACAGAGTTACAATAACCCTTTGTTCACC

TTCGGCCCTGGGACCAAAGTGGATATCAAACGAACTGTGGCTGCACCAT

CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGC

CTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTA

CAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT

GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA

GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG

GAGAGTGT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 5.24A.F3 (SEQ ID NO: 321)

DIQMTQSPSSLTASVGDRVTIICRASQPIGSYLNWYQQSPGKAPKLLIY

AASTLQSGVPSRFSGSGSGTDFTLNISGLQPEDFATYYCQQSYNNPLFT

FGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV

QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACE

VTHQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.8B.H4 (SEQ ID NO: 322)

GAGGTGCAGCTGGTGGAGTCTGGGGGAAGTCTGGTACGGCCGGGGGGGT

CCCTGCGACTCTCCTGTGCAGCCTCTGGATTCATCTTTGATGATTATGG

CATGAGTTGGGTCCGCCAAGTTCCAGGGGAGGGCCTGGAGTGGGTCGCC

GGCATTACTTGGGATGGCGTGAACACAGATTATGCAGACTCCGTGAAGG

GCCGCTTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTTTCTCCT

AATGAACAGTCTCAGAGCCGAGGACACGGCCCTGTATCACTGTGCGAGA

GCCAGATACTACCAAGGCACTGGCCTCCGGTCCTACCTCGACGAGTGGG

GCCAGGGAACCCTGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCCATC

GGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCC

GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGT

CGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGT

CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC

TCCAGCAACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACAAGC

CCAGCAACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGTCGA

GTGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTCCTC

TTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGG

TCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCCAGTT

CAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCA

CGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGTCCTCACCG

TTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTC

CAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAACCAAA

GGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGG

AGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTA

CCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAAC

AACTACAAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTTCTTCC

TCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGT

CTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAG

AAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.8B.H4 (SEQ ID NO: 323)

EVQLVESGGSLVRPGGSLRLSCAASGFIFDDYGMSWVRQVPGEGLEWVA

GITWDGVNTDYADSVKGRFTISRDNAKNSLFLLMNSLRAEDTALYHCAR

ARYYQGTGLRSYLDEWGQGTLVTVSSSTKGPSVFPLAPCSRSTSESTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLF

PPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPR

EEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKG

QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK

SLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 5.8B.H4 (SEQ ID NO: 324)

GACATCCAGATGACCCAGTCTCCATCCTCCGTGTCTGCATCTGTAGGAG

AAAGAGTCACTATCACTTGTCGGGCGACTCAGGGTATTGACAACTGGTT

GGCCTGGTATCAGCATAAACCAGGGAAAGCCCCGAAGCTCCTGATTTAT

GCTGCATCCACTTTGCAAAGTGGGGTCCCGTCCAGGTTCAGCGGCAGTG

GATCTGGGACAGATTTCACTCTCACCATCAGCAGCGTGCAGCCTGAAGA

TGTTGCAACTTACTTTTGTCAACAGGCTAAGAATTTCCCTCGGGGAGGA

TTCACTTTCGGCCCTGGGACCAAAGTCGCTCTCAAACGAACTGTGGCTG

CACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGG

AACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCC

AAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGG

AGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAG

CACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCC

TGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCA

ACAGGGGAGAGTGT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 5.8B.H4 (SEQ ID NO: 325)

DIQMTQSPSSVSASVGERVTITCRATQGIDNWLAWYQHKPGKAPKLLIY

AASTLQSGVPSRFSGSGSGTDFTLTISSVQPEDVATYFCQQAKNFPRGG

FTFGPGTKVALKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA

KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA

CEVTHQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 26.51.E1 (SEQ ID NO: 326)

CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGT

CCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAAATTTGC

CATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCA

GCTATAGCGTCTGATGGATATAATAAATACTATGCAGACTCCGTGAAGG

GCCAATTCACCGTCTCCAGAGACACTTCCAGGAACACGCTGTATCTCCA

AATGGACAGCCTGAGACCTGATGACACGGCTATTTATTACTGTGCGTAC

GGTCACTTGTCTTTTTGGTTCGACCCCTGGGGCCAGGGAACCCTGGTCA

CCGTCTCGAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCC

CTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTC

AAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTC

TGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACT

CTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAACTTCGGCACC

CAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGG

ACAAGACAGTTGAGCGCAAATGTTGTGTCGAGTGCCCACCGTGCCCAGC

ACCACCTGTGGCAGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAG

GACACCCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGG

ACGTGAGCCACGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGACGG

CGTGGAGGTGCATAATGCCAAGACAAAGCCACGGGAGGAGCAGTTCAAC

AGCACGTTCCGTGTGGTCAGCGTCCTCACCGTTGTGCACCAGGACTGGC

TGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCAGC

CCCCATCGAGAAAACCATCTCCAAAACCAAAGGGCAGCCCCGAGAACCA

CAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGG

TCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGT

GGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACACCT

CCCATGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCG

TGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGAT

GCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCT

CCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 26.51.E1 (SEQ ID NO: 327)

QVQLVESGGGVVQPGRSLRLSCAASGFTFSKFAMHWVRQAPGKGLEWVA

AIASDGYNKYYADSVKGQFTVSRDTSRNTLYLQMDSLRPDDTAIYYCAY

GHLSFWFDPWGQGTLVTVSSSTKGPSVFPLAPCSRSTSESTAALGCLVK

DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQ

TYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVQPNWYVDGVEVHNAKTKPREEQFNS

TFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQ

VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

MLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 26.51.E1 (SEQ ID NO: 328)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCCGCATCTGTAGGAG

ACAGAGTCACCATCACTTGCCGGGCAAGTCAGGACATTGGAAATGGCTT

AGGCTGGTATCAACAGATACCAGGGAAAGCCCCTAAGCGCCTGATCTAT

GCTGCATCCTCTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTG

GTTCTGGGACAGAGTTCACTCTCACAATCCACAGCCTGCAGCCTGAAGA

TTTTGCAACTTATTACTGTCTACAGCATAATTTTTACCCTCGCACTTTT

GGCCAGGGGACCAAGCTGGAGATCAAGCGAACTGTGGCTGCACCATCTG

TCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTC

TGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG

TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCA

CAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGAC

GCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTC

ACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG

AGTGT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 26.51.E1 (SEQ ID NO: 329)

DIQMTQSPSSLSASVGDRVTITCRASQDIGNGLGWYQQIPGKAPKRLIY

AASSLQSGVPSRFSGSGSGTEFTLTIHSLQPEDFATYYCLQHNFYPRTF

GQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV

THQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 22.21.A7 (SEQ ID NO: 330)

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCT

CAGTGAAGGTCTCCTGCAAGGCTTCTGGATACACCTTCACCGACTACTA

TATACACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGA

TGGATCAACCCTTATAGTGGTGGCACAAACTATGCACCGAAGTTTCAGG

GCAGGTTCACCATGGCCAGGGACACGTCCATCACCACAACCTACTTGGA

CCTGGGCAGGCTGACGTCTAGCGACACGGCCATTTATTTCTGTGCGAGA

GATTTCTTCAGAGCAGCAGCTGGCACGGCCGGAGACTACTGGGGCCAGG

GAACCCTGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCCATCGGTCTT

CCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTG

GGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGA

ACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGTCCTACA

GTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGC

AACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACAAGCCCAGCA

ACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGTCGAGTGCCC

ACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTCCTCTTCCCC

CCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACGT

GCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCCAGTTCAACTG

GTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCACGGGAG

GAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGTCCTCACCGTTGTGC

ACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA

AGGCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGGCAG

CCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGA

CCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAG

CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTAC

AAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTTCTTCCTCTACA

GCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTC

ATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGC

CTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 22.21.A7 (SEQ ID NO: 331)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIHWVRQAPGQGLEWMG

WINPYSGGTNYAPKFQGRFTMARDTSITTTYLDLGRLTSSDTAIYFCAR

DFFRAAAGTAGDYWGQGTLVTVSSSTKGPSVFPLAPCSRSTSESTAALG

CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSN

FGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREE

QFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQP

REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK

TTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 22.21.A7 (SEQ ID NO: 332)

GACATCGTGATGACCCAGTCTCCAGAAGACTCCCTGGCTGTGTCTCTGG

GCGAGAGGGCCACCATCAACTGCTCCAGCCAGAGTGCTTTATACAGCCC

CAGCAGTAAGACCTACTTAGCTTGGTACCAGCAGAGACCGGGACACCCT

CCTAAGCTTCTCATTTACTGGGCATCTACCCGGGTATCCGGGGTCCCTG

ACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCGG

CAGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGTACTATTAT

GGTACTGTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTG

TGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAA

ATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGA

GAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACT

CCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCT

CAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTC

TACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGA

GCTTCAACAGGGGAGAGTGT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 22.21.A7 (SEQ ID NO: 333)

ADIVMTQSPDSLAVSLGERATINCSSQSALYSPSSKTYLAWYQQRPGHP

PKLLIYWASTRVSGVPDRFSGSGSGTDFTLTIGSLQAEDVAVYYCQYYY

GTVTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR

EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKV

YACEVTHQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 22.18A.E9 (SEQ ID NO: 334)

CAGGTGCAGCTGCAGGAGTCGGGCCCAAGACTGGTGAAGCCTTCGGAGA

CCCTGTCCCTCACCTGCACTGTCTCTGGTGGGTCCATCAATAGTTATTA

TTGGAGTTGGATCCGGCAGCCCGTCGGGAAGGGACTGGAGTGGATTGGG

CGTATGTATCCCGGTGGTACCTCCAGTTACAATTCATCCCTCAAGAGTC

GAGTCATCATGTCGGTAGACACGTCGAAGAACCAGTTTTCTCTGAACCT

CACTTCTGTGACCGCCGCAGACACGGCCGTATATTTCTGTGCGAGAGAT

CCAACATATCACCATGGCACTAGTGGTTATGTGGGGACTTTTGATCTCT

GGGGCCAAGGGACAATGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCC

ATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACA

GCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGG

TGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGC

TGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTG

CCCTCCAGCAACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACA

AGCCCAGCAACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGT

CGAGTGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTC

CTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTG

AGGTCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCCA

GTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG

CCACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGTCCTCA

CCGTTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGT

CTCCAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAACC

AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGG

AGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTT

CTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAG

AACAACTACAAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTTCT

TCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAA

CGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACG

CAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 22.18A.E9 (SEQ ID NO: 335)

QVQLQESGPRLVKPSETLSLTCTVSGGSINSYYWSWIRQPVGKGLEWIG

RMYPGGTSSYNSSLKSRVIMSVDTSKNQFSLNLTSVTAADTAVYFCARD

PTYHHGTSGYVGTFDLWGQGTMVTVSSSTKGPSVFPLAPCSRSTSESTA

ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP

SSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP

REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTK

GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 22.18A.E9 (SEQ ID NO: 336)

GAAATAGTGATGACGCAGTCTCCAGCCACCCTGTCTGCGTCTCCAGGGG

AAAGAGTCACCCTCTCCTGCAGGGCCAGTCCGAGTGTTCGCAACAATTT

AGCCTGGTACCAGCAGAAACCTGGCCAGCCTCCTAGGCTCCTCATCTAT

GGTGCATCCACCAAGGTCATGGGTACTCCAACCAGGTTCAGTGGCAGTG

GGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGA

TTTTGCAGTTTATTACTGTCAGCAGTATAATAGCTGGCCTCCGTACACT

TTTAGCCAGGGGACCAAACTGGAGATCAAACGAACTGTGGCTGCACCAT

CTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGC

CTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTA

CAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTG

TCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCT

GACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA

GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGG

GAGAGTGT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 22.18A.E9 (SEQ ID NO: 337)

DIVMTQSPATLSASPGERVTLSCRASPSVRNNLAWYQQKPGQPPRLLIY

GASTKVMGTPTRFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNSWPPY

TFSQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK

VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYAC

EVTHQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.52.H10 (SEQ ID NO: 338)

GAGGTGCAGCTGGTGGAGTCGGGGGGAGGCCTGGTCAGGCCTGGGGAGT

CCCTGAGACTCTCCTGTGCAGGCTCTGGATTCACCTTCAGCATGTTTACC

CTGAACTGGGTCCGCCAGGCTCCAGGGAAGGGACTGGAGTGGGTCGCAT

CTATTAGTGGTAGTAGCAGTTTAGTGTTTCATGAAGACTCAGTGAAG

GGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCAGTATATCTGC

AAATGAACAGCCTGAGAGCCGAAGACACGGCTATTTATTACTGTGTGA

GAGGAGATAGTCGCGACTATTGGGGCCAGGGAACCCTGGTCACCGTCT

CGAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCT

CCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGA

CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACC

AGCGGCGTGCACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTACT

CCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAACTTCGGCACCCAGAC

CTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAG

ACAGTTGAGCGCAAATGTTGTGTCGAGTGCCCACCGTGCCCAGCACCAC

CTGTGGCAGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACAC

CCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTG

AGCCACGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGACGGCGTGG

AGGTGCATAATGCCAAGACAAAGCCACGGGAGGAGCAGTTCAACAGCAC

GTTCCGTGTGGTCAGCGTCCTCACCGTTGTGCACCAGGACTGGCTGAAC

GGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCAGCCCCCA

TCGAGAAAACCATCTCCAAAACCAAAGGGCAGCCCCGAGAACCACAGGT

GTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGC

CTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGT

GGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACACCTCCCAT

GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGAC

AAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATG

AGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGG

TAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.52.H10 (SEQ ID NO: 339)

EVQLVESGGGLVRPGESLRLSCAGSGFTFSMFTLNWVRQAPGKGLEWVA

SISGSSSLVFHEDSVKGRFTISRDNAKNSVYLQMNSLRAEDTAIYYCV

RGDSRDYWGQGTLVTVSSSTKGPSVFPLAPCSRSTSESTAALGCLVKD

YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQT

YTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVFLFPPKPKDT

LMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNST

FRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPM

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 5.52.H10 (SEQ ID NO: 340)

CAGTCTGTGTTGACGCAGCCGCCCTCAGTGTCTGCGGCCCCAGGACAGA

AGGTCACCATCTCCTGCTCTGGAAGGACCTCCAATATTGGAAATAACCA

TGTATCCTGGTACCAGCAATTCCCAGGAACAGCCCCCAAAGTCCTCATT

TATCGCAATGATAGGCGACCCTCAGGGATTCCTGATCGATTCTCTGGCT

CCAAGTCTGACACGTCAGCCACCCTGGGCATCACCGGGCTCCAGACTGG

GGACGAGGCCGATTATTACTGCGGAACATGGGACAACAGCCTGAGTGGT

TGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGTCAGCCCAAGG

CTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAAGC

CAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGTC

GTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGG

AGACCACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCCAGCAG

CTACCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAAAAGCTACAGC

TGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTG

CAGAATGCTCA

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 5.52.H10 (SEQ ID NO: 341)

QSVLTQPPSVSAAPGQKVTISCSGRTSNIGNNHVSWYQQFPGTAPKVLI

YRNDRRPSGIPDRFSGSKSDTSATLGITGLQTGDEADYYCGTWDNSLSG

WVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGV

VTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYS

CQVTHEGSTVEKTVAPAECS

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.15.C1 with an IgG1 Constant Region (SEQ ID NO: 342)

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAGGCCTGGGGCCTC

AGTGAAGGTCTCCTGTGAGACTTCTGGATATAGCTTCACCACTCATGAT

TTGAACTGGGTGCGACAGGCCGCTGGACAGGGGCTTGAGTGGATGGGAT

GGATGAACCCTAACACTGGTGACACATCCTACGCACAGAGGTTCCAGGG

CAGAGTCACCATGATCAGGGACGTCTCCATAAGTACAGCCTACTTGGAA

TTGACAGGCCTGACATTTGATGACACGGCCGTCTACTTCTGTGCGAGGT

CGAATTCTGCACCTGTTTCAACTCTTTTACCCGCTGATGCTTTTGATGT

CTGGGGCCAAGGGACAATGGTCACCGTCTCGAGTGCCTCCACCAAGGGC

CCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCA

CAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGAC

GGTGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCA

GCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCG

TGCCCTCCAGCAACTTCGGCACCCAGACCTACACCTGCAACGTAGATCA

CAAGCCCAGCAACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGT

GTCGAGTGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCT

TCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCC

TGAGGTCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTC

CAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAA

AGCCACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGTCCT

CACCGTTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAG

GTCTCCAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAA

CCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCG

GGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGC

TTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGG

AGAACAACTACAAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTT

CTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGG

AACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACA

CGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.15.C1 with an IgG1 Constant Region (SEQ ID NO: 343)

QVQLVQSGAEVKRPGASVKVSCETSGYSFTTDLNWVRQAAGQGLEWMGW

MNPNTGDTSYAQRFQGRVTMIRDVSISTAYLELTGLTFDDTAVYFCARS

NSAPVSTLLPADAFDVWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGT

AALGCLVKDYFPEPVTVSWNSGALTSGVTFPAVLQSSGLYSLSSVVTVP

SSSLGTQTYICNVNKPSNTKVDKKVEPKSCDKTTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSEDPEVKFNWYVDGVEVNAKTKP

REEQYNSTYRVVSVLTVLQDWLNGKEYKCKVSNKALPAPIEKTISKAKG

QPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMEALNYTQKSLS

LSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Chain Sequence of 5.15.C1 (SEQ ID NO: 344)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTATAGGAG

ACACAGTCACCATCACTTGCCGGGCAAGTCAGATCATTAACAGCTATTT

AAATTGGTATCAGCAAAAACCAGGGGAAGCCCCTAAACTCCTGATCTAT

GCTGTATCCAATTTGCACCGTGGGGTCCCCTCAAGGTTCAGTGGCAG

TGGGTCTGCGGCAGATTTCACTCTCACTATCAGTGGTCTGCAACCTGAA

GATTTTGCAACTTACTACTGTCAACAGACTTACACTACCGTTGCGATCA

CCTTCGGCCAAGGGACACGACTGGACATTAAACGAACTGTGGCTGCACC

ATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACT

GCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAG

TACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG

TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACC

CTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCG

AAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAG

GGGAGAGTGT

Protein Sequence Defining the Full Length Kappa Chain Sequence of 5.15.C1 (SEQ ID NO: 345)

DIQMTQSPSSLSASIGDTVTITCRASQIINSYLNWYQQKPGEAPKLLIY

AVSNLHRGVPSRFSGSGSAADFTLTISGLQPEDFATYYCQQTYTTVAIT

FGQGTRLDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV

QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVT

HQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.54.E6 with an IgG1 Constant Region (SEQ ID NO: 346)

CAGGTGCAGCTGGTGCAGTCTGGGGCGGAGGTGAAGAAGCCTGGGTCCT

CGGTGAACGTCTCCTGTAAGGCCTCCGCAGGGACCCTCAGCGGTTATACC

ATCAACTGGTTGCGCCAGGCCCCTGGACGAGGGTTTGAGTGGCTGGGAA

GGATCATCCCTCACCTTGGAATAGGAAACAACGCACATAACTGGGAGGC

CAGAGTCACCCTTACCGCCGACAAGTCCACGGACACTACCTACCTGGAG

TTGCGCGACCTGAGATCTGACGACGTGGCCATTTATTACTGCGCGGTG

GAGTTTTACCGGCTGGCAACGGTCACAACCCCAACCCTTGACTTCTGG

GGCCAGGGAACCCTGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCCAT

CGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGC

CGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTG

TCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTG

TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC

CTCCAGCAACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACAAG

CCCAGCAACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGTCG

AGTGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTCCT

CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAG

GTCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCCAGT

TCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCC

ACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGTCCTCACC

GTTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCT

CCAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAACCAA

AGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAG

GAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT

ACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAA

CAACTACAAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTTCTTC

CTCTAAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGT

CTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAG

AAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.54.E6 with an IgG1 Constant Region (SEQ ID NO: 347)

QVQLVQSGAEVKKPGSSVNVSCKASAGTLSGYTINWLRQAPGRGFEWLG

RIIPLGIGNNANWEARVTLTADKSTDTTYLELRDLRSDDVAIYYCAVEF

YRLATVTTPTLDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

GCLVKDYFPEPVTVSWNSGALTSGVTFPAVLQSSGLYSLSSVVTVPSSSLG

TQTYICNVNKPSNTKVDKKVEPKSCDKTTCPPCPAPELLGGPSVFLFPPKP

KDTLMISRTPEVTCVVVDVSEDPEVKFNWYVDGVEVNAKTKPREEQYNSTY

RVVSVLTVLQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMEALNYTQKSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Lambda Chain Sequence of 5.54.E6 (SEQ ID NO: 348)

TCCTATGTGCTGACTCAGCCACCCTCGGTGTCCGTGGCCCCAGGAACGA

CGGCCAGGATTACCTGTGAGGGGGACCACATTGGAGCTAAAAGTGTGCA

CTGGTACCAGAGGAAGCCAGGCCAGGCCCCTGTGTTGGTCGTCTATATGA

ATAGTGACCGGCCCTCAGGGATCCCTGAGCGATTGTCTGGCTCCAACTCT

GGGAACACGGCCACCCTGAGTATCAGCAGGGTCGAGGCCGAGGATGAGG

CCGACTATTATTGTCAGGTTTGGGATAGTTTTCGCGATCATCAGGTAT

TCGGCGGAGGGACCAAGTTGACCGTCCTGAGTCAGCCCAAGGCTGCCCC

CTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAAGCCAACAAG

GCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAG

TGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCAC

CACACCCTCCAAACAAGGCAACAACAAGTACGCGGCCAGCAGCTATCTG

AGCCTGACGCCTGAGCAGTGGAAGTCCCACAGAAGCTACAGCTGCCAGG

TCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAATG

TTCA

Protein Sequence Defining the Full Length Lambda Chain Sequence of 5.54.E6 (SEQ ID NO: 349)

SYVLTQPPSVSVAPGTTARITCEGDHIGAKSVHWYQRKPGQAPVLVVYM

NSDRPSGIPERLSGSNSGNTATLSISRVEAEDEADYYCQVWDSFRDHQV

FGGGTKLTVLSQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVT

VAWKADSSPVKAGVETTTPSKQGNNKYAASSYLSLTPEQWKSHRSYSCQ

VTHEGSTVEKTVAPTECS

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.55.D2 with an IgG1 Constant Region (SEQ ID NO: 350)

CAGGTCACCTTGAAGGAGTCTGGTCCTGCTATAGTGAAACCCACACAGA

CCCTCACGCTGACCTGCACCTTCTCTGGGTTCTCACTCCGAACTAGTG

GAGTGGGTGTGGGCTGGATCCGTCAGCCCCCAGGAAAGGCCCTTGAGTG

GCTTGCACTCATTTACTGGGATGATGATAAGCGCTACAACCCATCTCTG

AAGACCAGACTCACCATCACCAAGGACTCCTCCAGAAACCAGGTGTTCC

TCACAATGACCAACATGGACCCTGTGGACACAGCCACATACTTCTGTGC

ACACCGACAACATATTACAAACAGTTTTGGATTGGTTATTGCGAATGAT

GCTTTTGACATTTGGGGCCAAGGGACAATGGTCACCGTCTCGAGTGCCT

CCACCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCAC

CTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC

GAACCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGC

ACACCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAG

CGTGGTGACCGTGCCCTCCAGCAACTTCGGCACCCAGACCTACACCTGC

AACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGACAGTTGAGC

GCAAATGTTGTGTCGAGTGCCCACCGTGCCCAGCACCACCTGTGGCAGG

ACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATC

TCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCACGAAG

ACCCCGAGGTCCAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAA

TGCCAAGACAAAGCCACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTG

GTCAGCGTCCTCACCGTTGTGCACCAGGACTGGCTGAACGGCAAGGAGT

ACAAGTGCAAGGTCTCCAACAAAGGCCTCCCAGCCCCCATCGAGAAAAC

CATCTCCAAAACCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTG

CCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCC

TGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAA

TGGGCAGCCGGAGAACAACTACAAGACCACACCTCCCATGCTGGACTCC

GACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGT

GGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCA

CAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.55.D2 with an IgG1 Constant Region (SEQ ID NO: 351)

QVTLKESGPAIVKPTQTLTLTCTFSGFSLRTSGVGVGWIRQPPGKALEW

LALIYWDDDKRYNPSLKTRLTITKDSSRNQVFLTMTNMDPVDTATYFCA

RQITNSFGLVIANDAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSG

GTAALGCLVKDYFPEPVTVSWNSGALTSGVTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNKPSNTKVDKKVEPKSCDKTTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSEDPEVKFNWYVDGVEVNAKT

KPREEQYNSTYRVVSVLTVLQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMEALNYTQKS

LSLSPGK

Nucleic Acid Sequence Encoding the Full Length Lambda Chain Sequence of 5.55.D2 (SEQ ID NO: 352)

CAGTCTGCCCTGACTCAGCCTCCGTCCGCGTCCGGGTCTCCTGGACAGT

CAGTCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTCGTTATA

ATTATGTCGCCTGGTATCAACAACACCCAGGCAGAGCCCCCAGACTCA

TAATTTATGGGGTCACTAAGCGGCCCTCAGGGGTCCCTGATCGCTTC

TCTGGCTCCAAGTCTGGCAACACGGCCTCCCTGACCGTCTCTGGGCTCC

AGGCTGAAGATGAGGCTGATTATTATTGCAGTTCATATGCAGGCAGCA

ACTTTTTGGAGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT

CAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGG

AGCTTCAAGCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTA

CCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAG

GCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACG

CGGCCAGCAGCTACCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAG

AAGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACA

GTTGCCCCTACGGAATGTTCA

Protein Sequence Defining the Full Length Lambda Chain Sequence of 5.55.D2 (SEQ ID NO: 353)

QSALTQPPSASGSPGQSVTISCTGTSSDVGRYNYVAWYQQHPGRAPR

LIIYGVTKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCS

SYAGSNFLEVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVC

LISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPE

QWKSHRSYSCQVTHEGSTVEKTVAPTECS

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 22.14.A1 with an IgG1 Constant Region (SEQ ID NO: 354)

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCT

CGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATG

CAATCAACTGGGTGCGACAGGCCCCTGGACAAGGTCTTGAGTGGATGG

GAGGGATCATCCCTATGTTTGATACAGCAATCTACGCACAGATGTTC

CAGGGCAGAGTCACCATCACCGCGGACGAATCCACGAGCACAGCCTACAT

GGAGCTGAGCAGCCTGAGATCTGACGACACGGCCGTATATTACTGTGC

GAGAGATCGAAACGATTATTATGACAGTAGTGGTTATTCAGGCGCCTT

TGACCAGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGTGCCTCCA

CCAAGGGCCCATCGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTC

CGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA

CCGGTGACGGTGTCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACA

CCTTCCCAGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGT

GGTGACCGTGCCCTCCAGCAACTTCGGCACCCAGACCTACACCTGCAAC

GTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGACAGTTGAGCGCA

AATGTTGTGTCGAGTGCCCACCGTGCCCAGCACCACCTGTGGCAGGACC

GTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCC

CGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACC

CCGAGGTCCAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGC

CAAGACAAAGCCACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTC

AGCGTCCTCACCGTTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACA

AGTGCAAGGTCTCCAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCAT

CTCCAAAACCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCC

CCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGG

TCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGG

GCAGCCGGAGAACAACTACAAGACCACACCTCCCATGCTGGACTCCGAC

GGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGC

AGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAA

CCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 22.14.A1 with an IgG1 Constant Region (SEQ ID NO: 355)

QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAINWVRQAPGQGLEW

MGGIIPMFDTAIYAQMFQGRVTITADESTSTAYMELSSLRSDDTAVY

YCARDRNDYYDSSGYSGAFDQWGQGTLVTVSSASTKGPSVFPLAPS

SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVTFPAVLQSSGLYS

LSSVVTVPSSSLGTQTYICNVNKPSNTKVDKKVEPKSCDKTTCPPCPAP

ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSEDPEVKFNWYVDGV

EVNAKTKPREEQYNSTYRVVSVLTVLQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWE

SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMEAL

NYTQKSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Chain Sequence of 22.14.A1 (SEQ ID NO: 356)

GAAATTGTGTTGACGCAGTCTCCAGGCGCCCTGTCTTTGTCTCCAGGGG

AAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCT

ACTTAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCA

TCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGT

GGCAGTGGGTCTGGGACAGACTTCACTCTCACAATCAGCAGACTGGAGC

CTGAGGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCTC

GCACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGAACTGTGGCT

GCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTG

GAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGC

CAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAG

GAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCA

GCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGC

CTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTC

AACAGGGGAGAGTGTTAGAACGCGTG

Protein Sequence Defining the Full Length Kappa Chain Sequence of 22.14.A1 (SEQ ID NO: 357)

EIVLTQSPGALSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRL

LIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYG

SSPRTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF

YPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEK

HKVYACEVTHQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 26.53.B4 with an IgG1 Constant Region (SEQ ID NO: 358)

GAGGTGCAGCTGGTGGAGTCCGGGGGAGGCTTGGTCCAGCCTGGGGGGT

CCCTGAAACTCTCCTGTGCAGCCTCTGGGTTCAGCTTCAGTGGCTCTG

CTGTGGAATGGGTCCGCCAGGCTTCCGGGAGAGGGCTGGAGTGGATTG

GCCATATAAGAACCAAGACCAAAAATTACGCGACAGCGTATGCTGCG

TCGGTGCAAGGCAGGTTCACCATCTTCAGAGATGATTCAAGGAACACGG

CGTATCTGCAGATGAACAGTCTTAAAACCGAGGACACGGCCGTGTATTA

TTGTTCCAGACACATCGAATTTAGCAGTTCGTCCGGGCCCCAGATGG

GCCAGGGAACCCTGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCCAT

CGGTCTTCCCCCTGGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGC

CGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTG

TCGTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTG

TCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCC

CTCCAGCAACTTCGGCACCCAGACCTACACCTGCAACGTAGATCACAAG

CCCAGCAACACCAAGGTGGACAAGACAGTTGAGCGCAAATGTTGTGTCG

AGTGCCCACCGTGCCCAGCACCACCTGTGGCAGGACCGTCAGTCTTCCT

CTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAG

GTCACGTGCGTGGTGGTGGACGTGAGCCACGAAGACCCCGAGGTCCAGT

TCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCC

ACGGGAGGAGCAGTTCAACAGCACGTTCCGTGTGGTCAGCGTCCTCACC

GTTGTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCT

CCAACAAAGGCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAACCAA

AGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAG

GAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCT

ACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAA

CAACTACAAGACCACACCTCCCATGCTGGACTCCGACGGCTCCTTCTTC

CTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACG

TCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCA

GAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 26.53.B4 with an IgG1 Constant Region (SEQ ID NO: 359)

EVQLVESGGGLVQPGGSLKLSCAASGFSFSGSAVEWVRQASGRGLEW

IGIRTKTKNYATAYAASVQGRFTIFRDDSRNTAYLQMNSLKTEDTAV

YYCSRIEFSSSSGPQMGQGTLVTVSSASTKGPSVFPLAPSSKSTSG

GTAALGCLVKDYFPEPVTVSWNSGALTSGVTFPAVLQSSGLYSLSSVVT

VPSSSLGTQTYICNVNKPSNTKVDKKVEPKSCDKTTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSEDPEVKFNWYVDGVEVNAKT

KPREEQYNSTYRVVSVLTVLQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMEALNYTQKS

LSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Chain Sequence of 26.53.B4 (SEQ ID NO: 360)

GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGCG

ACACAGTCACCATCACTTGCCAGGCCAGTCAGAATATTATTACTTGG

TTGGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAACATCCTCATCT

ATAAGGCGTCTGGTTTAGAGAGTGGGGTCCCACCGAGGTTCAGCGGC

AGTGGGTCGGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTG

ATGATGTTGCAACTTATTATTGCCTACAATATAAAACTGAGCCGTGGA

CGTTCGGCCTAGGGACCAAGGTGGAGATCAGACGAACTGTGGCTGCA

CCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAA

CTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAA

AGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAG

AGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCA

CCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTG

CGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAAC

AGGGGAGAGTGT

Protein Sequence Defining the Full Length Kappa Chain Sequence of 26.53.B4 (SEQ ID NO: 361)

DIQMTQSPSTLSASVGDTVTITCQASQNIITWLAWYQQKPGKAPNIL

IYKASGLESGVPPRFSGSGSGTEFTLTISSLQPDDVATYYCLQYKT

EPWTFGLGTKVEIRRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY

PREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKH

KVYACEVTHQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.63.E2 (SEQ ID NO: 362)

GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGCCCAGCCGGGGGAGT

CCCTGAGACTCTCCTGTGCAGCCTCCGGATTCACCTTTAGTGCCTATT

GGATGAGCTGGGTCCGCCAGACTCCAGGGAAGGGGCTGGAGTGGGTGG

CCAACATTAACCAGGGTGGAGATAAGACAGACTATTTGGACTCTGTG

AAGGGCCGATTCACCGTCTCCAGAGACAATGCCAAGAACTTAGTGTTTC

TGCAAATGGCCAGCCTGAGAGCCGACGACACGGCCGTGTATTACTGTG

GGAGAGGTACAAACCAAGACTACTGGGGCCAGGGAACCCTGGTCACCG

TCTCGAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCT

CCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAA

GGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTG

ACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCT

ACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCA

GACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGAC

AAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGT

GCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCC

AAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC

GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGT

ACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGA

GCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCAC

CAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAG

CCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCC

CCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACC

AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCG

ACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAA

GACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGC

AAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCAT

GCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCT

CTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.63.E2 (SEQ ID NO: 363)

EVQLVESGGGLAQPGESLRLSCAASGFTFSAYWMSWVRQTPGKGLEW

VANINQGGDKTDYLDSVKGRFTVSRDNAKNLVFLQMASLRADDTAVY

YCGRGTNQDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAAL

GCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT

KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQP

ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHY

TQKSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Lambda Light Chain Sequence of 5.63.E2 (SEQ ID NO: 364)

CAGTCTGTGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGA

GGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAATATCGGAAGTAATA

ATGTATACTGGTACCAACAGGTCCCAGGAACGGCCCCCAAATTTCTCA

TCTATCCGAATAGTGAGCGGCCCTCAGGGGTCCCTGACCGATTCTCT

GCCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGACTCCGGT

CCGAGGATGAGGCTACTTATTACTGTGCAGCATGGGATGACAGCCTAA

GAACTTATGTCTTCGCATCTGGGACCAAGGTCACCGTCCTAGGTCAG

CCCAAGGCCAACCCCACTGTCACTCTGTTCCCGCCCTCCTCTGAGGAGC

TCCAAGCCAACAAGGCCACACTAGTGTGTCTGATCAGTGACTTCTACCC

GGGAGCTGTGACAGTGGCCTGGAAGGCAGATGGCAGCCCCGTCAAGGCG

GGAGTGGAGACCACCAAACCCTCCAAACAGAGCAACAACAAGTACGCGG

CCAGCAGCTACCTGAGCCTGACGCCCGAGCAGTGGAAGTCCCACAGAAG

CTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTG

GCCCCTACAGAATGTTCA

Protein Sequence Defining the Full Length Lambda Light Chain Sequence of 5.63.E2 (SEQ ID NO: 365)

QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNNVYWYQQVPGTAPKF

LIYPNSERPSGVPDRFSASKSGTSASLAISGLRSEDEATYYCAAWD

DSLRTYVFASGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLI

SDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQW

KSHRSYSCQVTHEGSTVEKTVAPTECS

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 5.64.G4 (SEQ ID NO: 366)

CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGT

CCCTGAGACTCTCCTGTGCAGCCTCCGGATTCACCCTCAGGAGTTATG

GCATGCACTGGGTCCGCCAGGCTCCAGGCAAGGGCCTGGAGTGGGTGG

CAGTTATATCATATGATGGAAGTAAGACATATTATAGAGACTCCGTG

AAGGGCCGATTCACCATCTCCAGAGACAATTCTAAGAACACACTGTATT

TGCAAATGAACAGCCTGCGAGTTGAGGACACGGCTGTATATTATTGTG

CGAAAGAGGATAATTTGGGATCTGATGTTTTTGATAGATGGGGCCAAG

GGACAATGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCCATCGGTCT

TCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCT

GGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGG

AACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTAC

AGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAG

CAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGC

AACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTC

ACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT

CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACC

CCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGG

TCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC

AAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC

CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCA

AGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAA

AGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCC

CGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAG

GCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCC

GGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCC

TTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG

GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTA

CACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 5.64.G4 (SEQ ID NO: 367)

QVQLVESGGGVVQPGRSLRLSCAASGFTLRSYGMHWVRQAPGKGLEWVA

VISYDGSKTYYRDSVKGRFTISRDNSKNTLYLQMNSLRVEDTAVYYCAK

EDNLGSDVFDRWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP

REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK

GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Lambda Light Chain Sequence of 5.64.G4 (SEQ ID NO: 368)

GACATCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAG

ACAGAGTTACCATCACTTGTCGGGCCAGTCAGAGTGCCAGTCAGTGGTT

GGCCTGGTATCAGCAAAAACCAGGGAAAGCCCCTAATCTCCTAATCTAT

AAGGCGTCTAATTTACATAGTGGGGTCCCATCAAGGTTCAGCGGCAGTG

GATCTGGGACCGAATTCACTCTCACCATCAGCAGCCTACAGCCTGATGA

TTTTGCAACTTATTACTGCCAACAATACAACATTTATCCGTGGACGTTC

GGCCAAGGGACCAAGGTGGAAGTGAGACGAACTGTGGCTGCACCATCTG

TCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTC

TGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG

TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCA

CAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGAC

GCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTC

ACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG

AGTGTT

Protein Sequence Defining the Full Length Lambda Light Chain Sequence of 5.64.G4 (SEQ ID NO: 369)

DIVMTQSPSTLSASVGDRVTITCRASQSASQWLAWYQQKPGKAPNLLIY

KASNLHSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNIYPWTF

GQGTKVEVRRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV

THQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 43.52.A11 (SEQ ID NO: 370)

CAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGGAGCCAGGGTCCT

CGGTGAGGGTCTCCTGCAAGGCTTCTGGACGCATCTTCCGGAATTATGC

TGTCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGGTGGGC

CGGTTCATCCCTTCGGAAGGAATAACAAACTACATTCCGACATTCCGGG

ACAGACTCACCTTTACTGCGGACAAGTCCACGAACACAGCCTTCATTGA

CCTGACTAACCTGAAATATGAGGACACGGCCATATATTACTGTGTGGGT

GGCAGGCCAGGCGCTTTCGTCCCCTTTGACTCCTGGGGCCAGGGAACCC

TGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCCATCGGTCTTCCCCCT

GGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGC

CTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAG

GCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTC

AGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTG

GGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCA

AGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAACTCACACATG

CCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTC

TTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGG

TCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTT

CAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCG

CGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG

TCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTC

CAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAA

GGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATG

AGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTA

TCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAAC

AACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCC

TCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGT

CTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAG

AAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 43.52.A11 (SEQ ID NO: 371)

QVQLVQSGAEVKEPGSSVRVSCKASGRIFRNYAVSWVRQAPGQGLEWVG

RFIPSEGITNYIPTFRDRLTFTADKSTNTAFIDLTNLKYEDTAIYYCVG

GRPGAFVPFDSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGC

LVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL

GTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP

REEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK

GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 43.52.A11 (SEQ ID NO: 372)

GAAATAGTGATGACGCAGTCTCCTGCCACCCTGTCTGTGTCTCCAGGGG

AAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTCAGGGGCAACTT

AGCCTGGTACCAGCAAAAACCTGGCCAGGCTCCCAGGCTTCTCATGTAT

GATGCTTCTACCAGGGCCACTAGTTTCCCAGCCCGGTTCAGTGGCAGTG

GGTCTGGGACAGAGTTCACTCTCACCATCAGCAGTGTGCAGTCTGAAGA

TTTTGCACTTTATTACTGTCAGCAGTATAATGACTGGCCCCGGACTTTT

GGCCAGGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTG

TCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTC

TGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG

TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCA

CAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGAC

GCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTC

ACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG

AGTGTT

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 43.52.A11 (SEQ ID NO: 373)

EIVMTQSPATLSVSPGERATLSCRASQSVRGNLAWYQQKPGQAPRLLMY

DASTRATSFPARFSGSGSGTEFTLTISSVQSEDFALYYCQQYNDWPRTF

GQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV

THQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 43.52.E12 (SEQ ID NO: 374)

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCT

CGGTGAGGGTCTCCTGCAGGGTTTCTGGAGGCAGTTTCTCCAGTTATGA

CGTACACTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGGTGGGA

AGGAGCGTCTCACGTGCTGACAGCTCAAGTCACACACGGGAGTTCGGGG

ACAGAGTCACGATTATCGCGGACAAATCCACGAGTACAGTTTATTTGAC

ACTGACCAGTCTGACCTCTGACGACACGGCCATCTATTACTGTGCGGCA

GGGGATTGTAGTGATGGCGGGTGCTTCCGCACACCCCTGCACATCTGGG

GCCAGGGCACCCTGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCCATC

GGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCG

GCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGT

CGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGT

CCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCC

TCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGC

CCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAA

AACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCG

TCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCC

GGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCC

TGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCC

AAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCA

GCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAA

GTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATC

TCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCC

CATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGT

CAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGG

CAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACG

GCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCA

GCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAAC

CACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 43.52.E12 (SEQ ID NO: 375)

QVQLVQSGAEVKKPGSSVRVSCRVSGGSFSSYDVHWVRQAPGQGLEWVG

RSVSRADSSSHTREFGDRVTIIADKSTSTVYLTLTSLTSDDTAIYYCAA

GDCSDGGCFRTPLHIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTA

ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP

SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA

KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

SKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN

HYTQKSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 43.52.E12 (SEQ ID NO: 376)

GAAATAGTGATGACGCAGTCTCCAGCCACTCTGTCTCTGTCTCCAGGGG

AAAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTCTGAGAACCAACTT

AGCCTGGTACCAGCAGCGACCTGGCCAGGCTCCCAGGCTCCTCATCTCT

GGGGCATCCACGAGGGCCACTGGTATCCCAGCCAGGTTCAGTGGCAGTG

GGTCTGGGACAGAATTCACTCTCACCATTAGGAGCCTGCAGCCTGAAGA

TTTTGCAGTTTATTACTGTCAACAGTATCATGACTGGCCTCGGACGTTC

GGCCAAGGGACCAAGGTGGATTTCAAACGAACTGTGGCTGCACCATCTG

TCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTC

TGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG

TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCA

CAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGAC

GCTGAGCAAAGCAGACTACGAGAAACACAAACTCTACGCCTGCGAAGTC

ACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAG

AGTGTTAG

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 43.52.E12 (SEQ ID NO: 377)

EIVMTQSPATLSLSPGERATLSCRASQSLRTNLAWYQQRPGQAPRLLIS

GASTRATGIPARFSGSGSGTEFTLTIRSLQPEDFAVYYCQQYHDWPRTF

GQGTKVDFKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ

WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKLYACEV

THQGLSSPVTKSFNRGEC

Nucleic Acid Sequence Encoding the Full Length Heavy Chain Sequence of 43.62.E2 (SEQ ID NO: 378)

GAGGTGCAGCTGGTGCAGTCTGGGGCAGAAGTGAAAAAGGCCGGGGAGT

CTCTGAGGATCTCCTGTAAGGGTTCTGGATACAACTTTAATAGCTATTG

GATTGGCTGGGTGCGCCAGATGCCCGGGAAAGGCCTGGAGTGGATGGCA

ATCATCTATCCTGCTGACTCTGACAGGAGATATGGCCCGTCCTTCCAAG

GCCAGGTCACCATCTCAGTCGACAAGTCTATTAACACCGCGTACTTGCA

GTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTATTGTGCCAGA

CTCCTCAGAGTTAGTACTGGTTGGGAAGATGCTTTTGATCTGTGGGGCC

AAGGGACAATGGTCACCGTCTCGAGTGCCTCCACCAAGGGCCCATCGGT

CTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCC

CTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGT

GGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCT

ACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCC

AGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCA

GCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACAAAAC

TCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA

GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGA

CCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGA

GGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAG

ACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCG

TCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTG

CAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCC

AAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCAT

CCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAA

AGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG

CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCT

CCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCA

GGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC

TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

Protein Sequence Defining the Full Length Heavy Chain Sequence of 43.62.E2 (SEQ ID NO: 379)

EVQLVQSGAEVKKAGESLRISCKGSGYNFNSYWIGWVRQMPGKGLEWMA

IIYPADSDRRYGPSFQGQVTISVDKSINTAYLQWSSLKASDTAMYYCAR

LLRVSTGWEDAFDLWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAA

LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS

SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK

TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS

KAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH

YTQKSLSLSPGK

Nucleic Acid Sequence Encoding the Full Length Kappa Light Chain Sequence of 43.62.E2 (SEQ ID NO: 380)

GACATCGTGATGACCCAGTCTCCAGACTCCCTGGTTGTGTCTCTGGGCG

AGAGGGCCACCATCAAGTGCCAGTCCAGCCAGAGTGTTTTGTACAGCTC

CACCAATAAGAACTATTTAGCCTGGTACCAGCAGAAATCGGGACAGCCA

CCTAAGCTACTCATTTACTGGGCCTCCACCCGGGAATCCGGGGTCCCTG

ACCGATTCATTGGTAGCGGCTCTAGGACAGATTTCACTCTCACCATCAG

CGACCTGCAGCCTGAGGATGCGGCAGTTTATTACTGTCAGCAGTATTAT

AGTGATTATCTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAA

CTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTT

GAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCC

AGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTA

ACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAG

CCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAA

GTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAA

AGAGCTTCAACAGGGGAGAGTGTTAG

Protein Sequence Defining the Full Length Kappa Light Chain Sequence of 43.62.E2 (SEQ ID NO: 381)

DIVMTQSPDSLVVSLGERATIKCQSSQSVLYSSTNKNYLAWYQQKSGQP

PKLLIYWASTRESGVPDRFIGSGSRTDFTLTISDLQPEDAAVYYCQQYY

SDYLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYP

REAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK

VYACEVTHQGLSSPVTKSFNRGEC

Example 2
Identification of Human S. aureus Antibodies

Healthy human subjects were recruited by posters located throughout the Roger Williams Medical Center campus. Blood from qualified subjects was processed through a Ficoll gradient to isolate PBMCs. Antibody-secreting plasma cells, identified by cell surface markers, were single-cell sorted into 96-well plates and subjected to RT-PCR to amplify antibody genes (FIG. 2A). As shown in FIG. 2A, the upper two panels show plasma cells with a clear CD38high/CD19+ population (R3 gate). The lower two panels show the lambda positive and kappa positive plasma cell populations (R4). Cells from the lambda and kappa positive populations were sorted into individual wells of 96-well PCR plates and heavy and light chains were recovered from single cells by RT-PCR with a cognate pair recovery rate of 73% (FIG. 2B). The variation in size between individual amplicons in the heavy chain gel suggests that a single heavy chain is being amplified in each well. Sequence data from cloned antibodies supports this conclusion. Amplified products (FIG. 2B) were cloned and expressed in mammalian cells (CHO-K1 cells) in 96-well format for screening.

Expressed antibodies were screened by ELISA to identify S. aureus-specific binders (FIG. 2C-E). Wells in which an antibody has been detected (values greater than two times background) are shaded, with color indicating relative expression levels with respect to background. Background is calculated as the average value of negative control wells (purple), left empty during sorting. FIG. 2D is a table showing data from plate 5.6 from a screening ELISA against S. aureus peptide antigens. Wells displaying 2× background (average value of purple wells) were scored as positive (e.g., well H9 was scored as positive). FIG. 2E is a table showing data from plate 5.6 from a screening ELISA against S. aureus surface proteins. Wells displaying 2× background (average value of purple wells) were scored as positive (e.g., wells H2 and A12 were scored as positive). Positives were reconfirmed through further ELISA testing (FIG. 2F), sequenced and expressed in a larger scale batch culture for in vitro testing and animal studies. Wells displaying 2× background (average value of purple wells) were scored as positive. Wells B12 and C12 were positive controls. Clones 5.6.H2 (wells B1, B2, B7 and B8) and 5.6.H9 (wells C7, C8) were confirmed as positives in this experiment, as well as several clones from other screening plates. Clone 5.6.A12 did not confirm and was discarded.

Example 3
Human Recombinant Polyclonal Anti-S. aureus Antibodies Protect Mice from Infection with Live S. aureus

A human recombinant polyclonal S. aureus antibody was generated by mixing individual antibodies (1.62.B9, 5.11.H10, 5.27.A11, 5.6.H2, and 5.6.H9; referred to herein as five antibody cocktail #1) equally to a total concentration of 1 mg/ml.

Mice were infected with a community associated methicillin-resistant (MRSA) strain, USA300, at a dose of 3.5×10⁸colony forming units (CFU) or 5×10⁸CFU, by intra-peritoneal injection. Immediately following infection, groups of 10 mice each were treated by intra-peritoneal injection with either PBS (control population), 110 mg/kg vancomycin, or 1.0 mg/kg of five antibody cocktail #1. Animals were observed at 2, 6, 18, 24, 48 and 72 hours post-treatment and live/dead status was noted.

At 3.5×10⁸CFU, all of the mice treated with five antibody cocktail #1 survived the full 72 hour study. At 5×10⁸CFU, 50% of the mice treated with five antibody cocktail #1 survived the full 72 hour study (FIG. 3). None of the PBS control mice survived to 72 hours at either dose of S. aureus. Vancomycin, the positive control, rescued all of the mice.

As shown in FIG. 4, the results of this experiment demonstrated that animals treated with PBS alone succumbed rapidly to infection with an LD₅₀of 2.75×10⁸CFU. Mice treated with five antibody cocktail #1 at a 1.0 mg/kg dose were fully protected from a dose of 3.5×10⁸CFU and were more resistant to infection with an LD₅₀of 5.0×10⁸CFU, which was approximately twice the LD₅₀dose for PBS treated animals. This represents a shift in the LD₅₀curve from 2.75×10⁸CFU to 5×10⁸CFU with the five antibody cocktail, which is a significantly stronger effect than has been previously demonstrated with passive immunotherapy approaches. Therefore, the results of this experiment suggest that mice treated with five antibody cocktail #1 are more resistant to S. aureus infection and that fully human recombinant polyclonal antibody therapy is capable of protecting mice from lethal infections of MRSA.

A second human recombinant polyclonal S. aureus antibody was generated by mixing individual antibodies (1.62.B9, 5.11.H10, 5.27.A11, 5.6.H2, 5.7.D3, 5.27.G2, and 8.11.G6; referred to herein as the seven antibody cocktail) equally to a total concentration of 1 mg/ml.

Mice were infected with a methicillin-sensitive (MSSA) strain, Wood46, at a dose of 2×10⁸colony forming units (CFU) or 4×10⁸CFU, by intra-peritoneal injection. Immediately following infection, groups of 5 mice each were treated by intra-peritoneal injection with PBS (control population), 110 mg/kg vancomycin, or 1.0 mg/kg of the seven antibody cocktail. Animals were observed at 2, 6, 18, 24, 48 and 72 hours post-treatment and live/dead status was noted.

At 2×10⁸CFU, all of the mice treated with the seven antibody cocktail survived the full 72 hour study, compared with 40% of the PBS control mice. At 4×10⁸CFU, 40% of the mice treated with the seven antibody cocktail survived the full 72 hour study (FIG. 5), compared with 10% of the PBS control mice. Vancomycin, the positive control, rescued all of the mice.

As shown in FIG. 6, the results of this experiment demonstrated that compared with animals treated with PBS alone, mice treated with the seven antibody cocktail at a 1.0 mg/kg dose were fully protected from a dose of 2×10⁸CFU and were more resistant to infection with a dose of 4.0×10⁸CFU. This represents a shift in the LD₅₀curve from 1.8×10⁸CFU to 3.75×10⁸CFU with the seven antibody cocktail, which is a significantly stronger effect than has been previously demonstrated with passive immunotherapy approaches. Therefore, the results of this experiment suggest that mice treated with the seven antibody cocktail are more resistant to S. aureus infection and that fully human recombinant polyclonal antibody therapy is capable of protecting mice from lethal infections of MSSA.

In a third study, a comparison was made between two five antibody cocktails, a ten antibody cocktail and a nineteen antibody cocktail. Five antibody cocktail #2 comprised antibodies 5.11.H10, 18.43.D8, 5.23.C9, 5.27.A11 and 5.6.H9. Five antibody cocktail #3 comprised antibodies 22.18.E9, 5.52.H10, 9.51.H9, 8.51.G10 and 5.23.C12. The ten antibody cocktail comprised antibodies 5.11.H10, 18.43.D8, 5.23.C9, 5.27.A11, 5.6.H9, 22.18.E9, 5.52.H10, 9.51.H9, 8.51.G10 and 5.23.C12. The nineteen antibody cocktail comprised antibodies 5.11.H10, 18.43.D8, 5.23.C9, 5.27.A11, 5.6.H9, 22.18.E9, 5.52.H10, 9.51.H9, 8.51.G10, 5.23.C12, 5.24.F3, 5.24.A7, 5.8.H4, 26.51.E1, 5.19.F12, 8.51.G11, 22.22.E7, 22.21.A7, and 5.17.F8. In each cocktail, component antibodies were mixed at equal ratios to a total concentration of 1 mg/ml.

Mice were infected with a community associated methicillin-resistant (MRSA) strain, USA300, at a dose of 1×10⁹colony forming units (CFU) by intra-peritoneal injection. Immediately following infection, groups of 8 mice each were treated by intra-peritoneal injection with PBS (control population), 10 mg/kg vancomycin, or 1.0 mg/kg of antibody cocktail. Animals were observed at 8, 16, 24, 32, 48, 56 and 72 hours post-treatment and live/dead status was noted.

At 1×10⁹CFU, all of the mice treated with either five antibody cocktail #2 or five antibody cocktail #3 survived the full 72 hour study, compared with 50% of the PBS control mice (FIG. 7). 75% of the mice treated with either the ten antibody cocktail or the nineteen antibody cocktail survived the full 72 hour study. Vancomycin, the positive control, rescued all of the mice.

Example 4
Antibody Reactivity Against Various S. aureus Strains

In this example, the antibodies disclosed herein were tested for reactivity against twelve different S. aureus strains grown on Tryptic Soy Agar (TSA) medium. The skilled person would understand that TSA is one or many conditions on which S. aureus may be grown and each conditions may result in the expression of a different proteome.

Each bacterial strain was spread on TSA and a single colony from each strain was used to inoculate a 5 ml trypticase soy broth (TSB) culture. The cultures were grown at 37° C. and then diluted before spread plating on TSA plates. The plates were grown overnight before being harvested. The bacteria were washed with PBS. The supernatants were filtered and stored at −20° C. before use. ELISA plates were coated with the supernatants, placed in an azide blocking buffer. The ELISA was run against the 26 different antibody clones as 1:10 diluted Fab fragments both in the presence of a protein A block. Any Fab that was reactive as determined by being sufficiently above background was marked with a (+), any Fab which was highly reactive was designated (++). Any FAb which was not reactive was designated with a (−), as is reflected in Table 4. The number of anti-S. aureus antibodies reacting with various S. aureus strains is shown in FIG. 8

The results suggest that not all antibodies bind each strain of S. aureus. A shown in Table 4, each different strain has a subset of different antibodies which bind. It is contemplated herein that these results reflect the different genomes and proteomes expressed by each strains. Under TSA conditions, antibodies 5.6.H9, 5.55.D2, 22.18A.E9, 9.51.H9, 5.11.H10, 5.23.C12, 5.52.H10, 18.43.D8, 8.51.G10 and 8.51.G11 each reacted with 8 or more S. aureus strains tested.

Example 5
In Vitro Opsonization of S. aureus in Human Blood is Augmented by Specific Antibody Cocktails

In this example, the capacity of specific antibody cocktails to enhance the opsonization of S. aureus bacteria by human blood cells was tested.

The following antibody cocktails were tested: antibody cocktail #1 was a five antibody cocktail including antibodies 5.11.H10, 5.23.C9, 5.52.H10, 26.51.E1 and 22.21.A7 at a total concentration of 1.0 mg/ml; antibody cocktail #2 was a five antibody cocktail including antibodies 5.11.H10, 5.27.A11, 5.6.H9, 18.43.D8 and 5.23.C9 at a total concentration of 1.0 mg/ml; and antibody cocktail #3 was a three antibody cocktail including antibodies 5.11.H10, 5.23.C9 and 5.52.H10 at a total concentration of 1.0 mg/ml.

100 μl of antibody (100 μg total) of each of antibody cocktails 1, 2, and 100 μl of S. aureus strain Wood-46 bacteria (1×10⁶cells) were mixed and incubated for 30 minutes at 37° C. 100 μl of heparinized human blood was added to the antibody/bacteria suspension. The bacteria were counted at time=0 and after a one hour incubation by taking samples from the 300 μl volume and plating serial dilutions on TSA. The percent killing is calculated as [(Bacteria, Time=0 h)−Bacteria, Time=1 h)]/(Bacteria, Time=0)×100%.

Antibody cocktails #1 and #3 each enhanced the ability of white blood cells to opsonize the S. aureus strain (FIG. 9). Antibody cocktail #2, which had previously been shown to provide protection in mice infected with a dose of 1×10⁹CFUs of USA300 strain (see Example 3) and contains an antibody against the cell surface (e.g., 5.11.H10), did not enhance opsonization suggesting that opsonization is one part of the criteria needed to provide protection in vivo. The data also suggests that opsonization of S. aureus in human blood is enhanced by polyclonal antibodies, e.g., polyclonal antibodies that contain a mixture of cell surface binding antibodies with other antibodies targeting other cellular mechanisms.

TABLE 4

Common
Anti-S. Aureus Antibodies

Strain
Name
Phenotype
5.6.H9
5.11.H10
5.27.A11
5.17.F8**
18.43.D8
5.19.F12
8.51.G11

BAA-1717*
USA300
MRSA
++
+
+
+
++
++
++

10832*
Wood-46
MSSA
++
++
−
−
−
−
−

NRS071
Sanger 252
HA-MRSA
++
++
++
−
+
−
++

NRS100
COL
HA-MRSA
++
++
++
−
++
++
++

NRS382
626
HR-MRSA
++
−
−
−
−
−
++

NRS384
LAC
CA-MRSA
++
+
+
−
++
++
++

NRS123
MW2
CA-MRSA
++
++
++
−
++
−
++

NRS001
Mu50
VISA
++
++
++
++
++
−
−

NRS072
Sanger 476
CA-MSSA
++
++
++
−
++
−
−

NRS102
Reynolds

++
+
−
−
−
−
++

NRS111
FRI913

++
−
−
−
+
−
++

NRS144
RN4220
MSSA
+
++
+
−
++
+
−

(Lab Strain)

Anti-S. Aureus Antibodies

Strain
8.51.G10
22.22.E7
5.23.C9
5.23.C12
9.51.H9**
5.24A.F3
5.24A.A7
5.8B.H4
5.52.H10

BAA-1717*
++
−
+
+
++
+
−
−
+

10832*
−
+
++
++
+
−
++
++
++

NRS071
++
−
−
+
++
++
−
−
++

NRS100
++
−
+
+
++
++
−
−
++

NRS382
++
−
−
−
++
++
−
−
−

NRS384
++
−
+
+
++
++
−
−
++

NRS123
++
−
−
++
++
++
−
−
++

NRS001
−
+
−
++
++
−
−
−
++

NRS072
−
−
−
++
++
++
−
−
++

NRS102
++
−
++
+
+
+
−
−
+

NRS111
++
−
−
−
++
+
−
−
−

NRS144
−
−
−
++
++
−
−
−
+

Anti-S. Aureus Antibodies

Strain
22.18A.E9
22.21.A7**
5.15.C1
5.54.E6**
5.55.D2
26.51.E1
22.14.A1
26.53.B4

BAA-1717*
−
−
+
−
+
−
−
−

10832*
−
++
+
−
+
−
++
+

NRS071
++
−
+
−
++
−
−
+

NRS100
++
−
++
−
++
−
−
++

NRS382
++
−
−
−
++
−
−
−

NRS384
++
−
++
−
++
−
−
+

NRS123
++
−
++
−
++
−
−
+

NRS001
−
−
++
−
−
−
−
++

NRS072
++
−
++
−
++
−
−
++

NRS102
++
−
−
−
++
−
++
+

NRS111
++
−
−
−
−
−
−
−

NRS144
−
−
−
−
−
−
−
++

Strains were obtained from either the America Tissue Culture Collection (ATCC) or from National Repository for Staphylococcus aureus. Strains obtained from the ATCC are designated with an *.

**Antibody expression may be underrepresented in this experiment.

INCORPORATION BY REFERENCE

The entire disclosure of each of the patent documents and scientific articles referred to herein is incorporated by reference for all purposes.

EQUIVALENTS

The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting on the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and the range of equivalency of the claims are intended to be embraced therein.

	Number	Date	Country
	61379580	Sep 2010	US
	61380934	Sep 2010	US

	Number	Date	Country
Parent	13820238		US
Child	13951645		US

Staphylococcus aureus Specific Human Recombinant Polyclonal Antibodies and Uses Thereof

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