Anti-BCMA antibody and method of making and using thereof

Abstract

Disclosed herein is a B cell maturation antigen (BCMA) binding peptide having binding specificity to human BCMA. The BCMA binding peptide comprises a variable heavy (VH) chain and a variable light (VL) chain. The VH chain comprises complementarity determining regions (CDRs) H1, H2, and H3 selected from defined VH CDR sequences, and the VL chain comprises CDRs L1, L2, and L3 selected from defined VL CDR sequences. The BCMA binding peptide exhibits specific binding to human BCMA and may be used in various antibody formats, compositions, and applications.

Description

SIBA043PCT PATENTANTI-BCMA ANTIBODY AND METHOD OF MAKING AND USING THEREOF CROSS REFERENCE TO RELATED APPLICATIONSThis application claims priority to U. S. Provisional Patent Application No. 63 / 746,237, filed January 16, 2025, the entire disclosure of which is incorporated by reference herein in its entirety for all purposes.TECHNICAL FIELDThis disclosure relates generally to the field of immunology and molecular biology, and more particularly to B cell maturation antigen (BCMA) binding molecules, including antibodies, antibody fragments, immunoconjugates, pharmaceutical compositions, and methods of making and using the same for diagnostic and therapeutic applications.SEQUENCE LISTINGThis application contains a computer readable Sequence Listing which has been submitted in XML file format via USPTO Patent Center, the entire content of which is incorporated by reference herein in its entirety. The Sequence Listing XML file submitted via USPTO Patent Center is entitled “SIBA043PCT.xml”, was created on January 13, 2026, and is 107,000 bytes in size.BACKGROUNDUnless otherwise indicated herein, the materials described in this section are not prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.Multiple myeloma (MM) is a clonal plasma cell disorder that makes up approximately 18% of all hematologic neoplasms and 1.8% of all cancers in the US. Annually, approximately 4.5-6 cases are reported per 100,000 individuals1-3. MM is characterized by an uncontrolled proliferation of plasma cells within the bone marrow, leading to excessive production of abnormal immunoglobulins, calcium elevation, renal dysfunction, anemia, and bone disease4. The pathogenesis of MM involves multiple factors, including the aberrant activation of intracellular signaling pathways that play critical roles in the proliferation, migration, and drug resistance of malignant cells1-3. Therapy for MM initiates with autologous stem cell transplant, followed by proteasome inhibitors, immunomodulatory drugs, and / or anti-CD38 monoclonal antibodies1-4. In newly diagnosed MM patients, these treatments can lead to an overall survival (OS) of 10 years2. Despite this improved outcome, MM remains incurable, and patients will experience relapse and progressively shorter remissions after each line of therapy. Often, for patients with MM refractory to multiple lines of therapy, limited options exist, and the OS is less than one year1-2. Therefore, a critical need remains for novel therapies, especially in patients with relapsed / refractory multiple myeloma (RRMM).B cell maturation antigen (BCMA, CD269, TNFRSF17) is found on the surface of B cells and is overexpressed on malignant plasma cells. BCMA is a member of the tumor necrosis factor receptor (TNFR) superfamily and involved in the regulation of B cell maturation and survival1. BCMA is a 184 amino acid type III transmembrane glycoprotein with an N-terminal extracellular conserved motif of 6 cysteines5. Surface expression is limited to differentiated plasma cells and plasmablasts, and is nearly absent on naive B cells, memory B cells, and non-hematopoietic tissues1. This selective expression isSIBA043PCT PATENTessential for plasma cell proliferation, migration, and survival. Agonist ligands for BCMA include APRIL (A proliferation-inducing ligand) and BAFF (B-cell activating factor), both involved in the maturation and differentiation of plasma cells1. APRIL has a higher avidity to BCMA; however, BCMA binding either APRIL or BAFF induces a downstream cascade of signaling pathways such as PI3K / Akt, RAS / MAPK, and NF-kB4. Under pathological conditions, BCMA is overexpressed on nearly all MM tumor cells. Further, in MM patients, APRIL and BAFF serum levels are 5-fold higher than in healthy patients2. Due to the highly selective nature of BCMA, APRIL, and BAFF, these ligand / receptor interactions may pose as a potential therapeutic target for MM treatment. Indeed, studies using a mouse xenograft model have demonstrated that these pathways, and therefore MM cell proliferation, can be reduced by a monoclonal antibody directed against APRIL6. Therefore, anti-BCMA immunotherapies, including those with APRIL inhibition, have the potential to improve overall survival rates in MM patients.Currently, multiple BCMA-targeted MM immunotherapies exist, including chimeric antigen receptor T cells (e.g., Idecabtagene Vicleucel and Ciltacabtagene Autoleucel), bispecific T-cell engagers (e.g., Teclistamab), and antibody drug conjugates (ADC) (e.g., Belantamab mafodotin)1'2. According to 1st Oncology, of approximately 166 anti-BCMA therapeutics, 154 have been developed to treat myeloma, and 51 are listed as antibodies. Teclistamab (TECVAYLI®), developed by lanssen Biotech and lohnson & Johnson, is a T-cell-redirecting bispecific antibody that targets CD3 on the surface of T cells and BCMA on the surface of myeloma cells. In clinical trials, Teclistamab demonstrated a single-agent overall response rate (ORR) of 63% and a median duration of response of 18.4 months in a heavily pretreated population. Based on this promising data, it received accelerated US FDA approval in November of 2022. However, treatment with Teclistamab has led to multiple adverse effects, including cytokine release syndrome and hematological toxicities2-7'8. Belantamab mafodotin (Blenrep), is a first-in-class antibody drug conjugate, developed by GlaxoSmithKline and Seattle Genetics. The humanized anti-BCMA IgGl monoclonal antibody is covalently linked to the microtubule inhibitor monomethyl auristatin F (MMAF). In addition to ADC activity, antibody treatment induces antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In 2020, belantamab mafodotin was approved by the US FDA as a monotherapy for relapsed myeloma patients with prior treatments. A multicenter phase 1 trial (DREAMM1) with 73 RRMM patients led to an ORR of 60% and progression-free survival of 12 months with adverse effects that included corneal toxicity and thrombocytopenia1'2’9. However, in 2022, belantamab mafodotin was withdrawn from US marketing authorization due to unfavorable outcomes of its phase III trial (DREAMM3) that did not meet the requirements of the US FDA accelerated approval regulation3. The majority of antibodies under development have shown promising pre-clinical and clinical data, and at least three have once or now been approved for market (Belantamab mafodotin, GlaxoSmithKline; Elranatamab, Pfizer; and Teclistamab, Johnson & Johnson). However, despite these advances, existing therapies suffer from limitations including safety, durability, or target engagement, a need remains for the development of high affinity antibody therapeutics with minimal adverse effects.SUMMARYThe following summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, embodiments, and features described above, further aspects,SIBA043PCT PATENTembodiments, and features will become apparent by reference to the drawings and the following detailed description.The present disclosure relates to, among others, B cell maturation antigen (BCMA) binding molecules, antibodies, and related compositions and methods, including antigen-binding peptides, monoclonal antibodies, antibody fragments, immunoconjugates, pharmaceutical compositions, and therapeutic uses thereof.In one aspect, the disclosure provides BCMA binding peptides having binding specificity to human BCMA. The BCMA binding peptides comprise a variable heavy (VH) chain and a variable light (VL) chain, wherein the VH chain comprises complementarity determining regions (CDRs) Hl, H2, and H3 selected from VH CDR sequences disclosed herein, and the VL chain comprises CDRs LI, L2, and L3 selected from VL CDR sequences disclosed herein.In one embodiment, the BCMA binding peptide may include a variable heavy (VH) chain having complementarity determining region (CDR) Hl, CDRH2, and CDRH3 of SEQ ID NO: 81, 82, and 83; SEQ ID NO: 87, 88, and 89; or SEQ ID NO: 93, 94, and 95. In one embodiment, the BCMA binding peptide may include a variable light (VL) chain having CDR LI, CDR L2, and CDR L3 of SEQ ID NO: 84, 85, and 86; SEQ ID NO: 90, 91, and 92; or SEQ ID NO: 96, 97, and 98.In one embodiment, the BCMA binding peptide may include the VH chain having the (CDR) Hl, CDR H2, and CDR H3 of SEQ ID NO: 81, 82, and 83; and the VL chain having CDR LI, CDR L2, and CDR L3 of SEQ ID NO: 84, 85, and 86. In one embodiment, the BCMA binding peptide may include the VH chain having the (CDR) Hl, CDR H2, and CDR H3 of SEQ ID NO: 87, 88, and 89; and the VL chain having CDR LI, CDR L2, and CDR L3 of SEQ ID NO: 90, 91, and 92. In one embodiment, the BCMA binding peptide may include the VH chain having the (CDR) Hl, CDR H2, and CDR H3 of SEQ ID NO: 93, 94, and 95; and the VL chain having CDR LI, CDR L2, and CDR L3 of SEQ ID NO: 96, 97, and 98.In one embodiment of the BCMA binding peptide, the VH chain may have an amino acid sequence having at least 80%, 85%, 92%, 95%, 98%, or 100% sequence identity to SEQ ID NO. 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 49, 54, 56, 58, 60, 62, 64, 66, 68. In one embodiment, the VL chain may have an amino acid sequence having at least 80%, 85%, 92%, 95%, 98%, or 100% sequence identity to SEQ ID NO. 3, 7, 11, 15, 19, 23, 27, 31, 35, 36, 39, 47, 50, 53, 55, 57, 59, 61, 63, 65, 67.In some embodiments, the BCMA binding peptides are provided in various antibody formats, including single-chain variable fragments (scFv), Fab fragments, and full-length monoclonal antibodies (mAbs). In certain embodiments, the BCMA binding peptides comprise scFv domains or Fab regions having binding specificity to BCMA.In some embodiments, the scFv domain comprises an amino acid sequence having at least 80%, 85%, 92%, 95%, 98%, or 100% sequence identity to SEQ ID NO. 75, 76, 77, 78, 79, or 80. In some embodiments, the scFv domain includes an affinity tag, such as a histidine residue linked to one or more termini of the scFv domain.In some embodiments, the Fab region may include the VH having at least 80%, 85%, 92%, 95%, 98%, or 100% of sequence identity to SEQ ID NO: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, or 48, and the VL having at least 80%, 85%, 92%, 95%, 98%, or 100% of sequence identity to 3, 7, 11, 15, 19, 23, 27, 31, 35, 36, 39, or 47.SIBA043PCT PATENTIn some embodiment, the Fab region has LCVR and HCVR selected from SEQ ID NO: 3 and 4, SEQ ID NO: 7 and 8, SEQ ID NO: 11 and 12, SEQ ID NO: 15 and 16, SEQ ID NO: 19 ad 20, SEQ ID NO: 36 and 44, SEQ ID NO: 39 and 40, SEQ ID NO: 47 and 48, SEQ ID NO: 23 and 24, SEQ ID NO: 27 and 28, SEQ ID NO: 31 and 32, or SEQ ID NO: 35 and 36.In some embodiments, the Fab region may be operably linked to an Fc domain to form a Fab-monoFc fusion protein. In one embodiment the Fc domain comprises an amino acid sequence having at least 80%, 85%, 92%, 95%, 98%, or 100% sequence identity to SEQ ID NO: 51. In some embodiments, the Fab region may be linked to a kappa light chain. In one embodiment, the kappa light chain comprises an amino acid sequence having at least 80%, 85%, 92%, 95%, 98%, or 100% sequence identity to SEQ ID NO: 52.In another aspect, the disclosure further provides isolated monoclonal antibodies comprising the BCMA binding peptides described herein.In one embodiment, the isolated mAb comprises an amino acid sequence having at least 98%, 95%, or 92% of sequence identity to SEQ ID NO: 3, 4, 7, 8, 11, 12, 15, 16, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 44, 47, 48, 49, 50, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 75, 76, 77, 78, 79, or 80. In one embodiment, the isolated mAb comprises a light chain (LC) having an amino acid sequence having at least 80%, 85%, 92%, 95%, 98%, or 100% of sequence identity to SEQ ID NO: 50, 53, 55, 57, 59, 61, 63, 65, or 67. In one embodiment, the isolated mAb comprises a heavy chain (HC) having an amino acid sequence having at least 80%, 85%, 92%, 95%, 98%, or 100% of sequence identity to SEQ ID NO: 49, 54, 56, 58, 60, 62, 64, 66, or 68.In one embodiment, the isolated mAb comprises the LC and HC selected from SEQ ID NO: 50 and 49, SEQ ID NO: 53 and 54, SEQ ID NO: 55 and 56, SEQ ID NO: 59 and 60, SEQ ID NO: 57 and 58, SEQ ID NO: 61 and 62, SEQ ID NO: 63 and 64, SEQ ID NO: 65 and 66, and SEQ ID NO: 67 and 68.In various embodiments, the monoclonal antibodies are humanized antibodies, chimeric antibodies, recombinant antibodies, or immunoglobulin G (IgG) antibodies, including IgGl antibodies. In further embodiments, the antibodies are bispecific, trispecific, or multispecific antibodies.In another aspect, the disclosure provides nucleic acids encoding the BCMA binding peptides or monoclonal antibodies described herein, as well as expression vectors comprising such nucleic acids. Host cells comprising the nucleic acids or expression vectors are also provided, including prokaryotic and eukaryotic host cells. Methods of producing the monoclonal antibodies are further provided, including culturing host cells under conditions suitable for expression of the antibodies.In additional aspects, the disclosure provides immunoconjugates comprising a BCMA binding peptide or monoclonal antibody conjugated to a drug unit through a linker. In certain embodiments, the linker comprises one or more covalent bonds selected from ester, ether, amine, amide, disulfide, imide, sulfone, phosphate, phosphorus ester, peptide, hydrazone, or combinations thereof. In some embodiments, the drug unit comprises a cytotoxic agent, an immune regulatory reagent, or a combination thereof. Exemplary cytotoxic agents include growth inhibitory agents and chemotherapeutic agents, such as tubulin binders, DNA intercalators, DNA alkylators, enzyme inhibitors, immune modulators, antimetabolites, radioactive isotopes, or combinations thereof.The disclosure further provides pharmaceutical compositions comprising a BCMA binding peptide, monoclonal antibody, or immunoconjugate described herein, optionally together with aSIBA043PCT PATENTpharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical compositions further comprise one or more additional agents, such as radionuclides, toxins, therapeutic agents, or chemotherapeutic agents.In another aspect, the disclosure provides methods for treating or preventing diseases or conditions associated with BCMA expression, including cancers, autoimmune diseases, and infectious diseases. The methods comprise administering to a subject an effective amount of a BCMA binding peptide, monoclonal antibody, immunoconjugate, or pharmaceutical composition described herein. In certain embodiments, the cancer comprises BCMA-expressing cells. In further embodiments, the methods include co-administering one or more additional therapeutic agents.In still another aspect, the disclosure provides solutions comprising effective concentrations of the BCMA binding peptides, monoclonal antibodies, or immunoconjugates described herein, including solutions present in blood plasma of a subject.BRIEF DESCRIPTION OF THE DRAWINGSThe foregoing and other features of this disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments arranged in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which:FIGURE 1 shows the result of B-cell culture screen by direct sandwich ELISA indicating that of 91 clones screened, 88% bound human BCMA;FIGURE 2 shows the result of chimeric screen by flow cytometry indicating that three selected candidates bound human BCMA, 1343B4, 1346H10, and 1347F7, and that 1343B4 bound both human and cynomolgus BCMA with minimal background binding;FIGURE 3 shows the result of bio-layer interferometry indicating that (FIG.3A) humanized antibodies, 1343B4, 1347F7 and 1346H10, bound recombinant human BCMA with high affinity at KD values within a 2 to 40 nM range; (FIG.3B) humanized 1343B4 also bound recombinant cynomolgus monkey BCMA with KD values of ~ 13 nM while humanized 1346F7 did not bind cynomolgus monkey BCMA; and (FIG. 3C) control antibodies, S1-43C1 (Amgen Anti-BCMA 2A1) and SL43C3 (Seagen Anti-BCMA hSG16.17), bound recombinant human BCMA with KD values in 2 to 4 nM range, but only SI-43C1 (Amgen Anti-BCMA 2A1) bound cynomolgus monkey with a KD value of - 40 nM;FIGURE 4 shows the result of humanized screen by flow cytometry indicating that (FIG. 4A) 1343B4 BSM and FRS scFv bound both human and cynomolgus monkey BCMA, while 1346H10 did not retain suitable binding after humanization and 1347F7 BSM and FRS scFv bound human BCMA, but not cyno BCMA; and (FIG.4B) the control SI-43C1 bound both human and cynomolgus monkey BCMA and the control SI-43 C3 bound only human BCMA while the negative control mAb only bound the negative control transfected cells;FIGURE 5 shows the result of antibody binding by Bio-Layer Interferometry indicating cross-species OCTET binding of humanized anti-BCMA mAb, 1343B4 FRS and SL43C4 control mAb, to mouse and rat BCMA, where 1343B4 FRS bound human BCMA with an affinity of 0.6 nM but did not bind mouse or rat BCMA, while control antibody, SL43C4 (Janssen anti-BCMA BCMB69) bound both mouse and rat BCMA with low affinity;SIBA043PCT PATENTFIGURE 6 depicts hierarchical clustering of humanized anti-BCMA mAb, 1343B4 FRS, and three comparator antibodies in the bin groups, where each square represents a separate bin, dotted arrows between bins represented unidirectional blocking, 1343B4 FRS was bidirectionally blocked by SI-43C2 (GSK), SI-43 C4 (Janssen), and SI-43 C3 (SEAGEN), indicating all antibodies bind at or near the same epitope on human BCMA, specially, 1343B4 FRS was unidirectionally blocked by a control antibody indicative of partial overlap epitopes;FIGURE 7 shows the result of bio-layer interferometry indicating that humanized antibodies 1343B4 (BSM and FRS) and 1346F7 (BSM and FRS) blocked APRIL binding to human BCMA; and FIGURE 8 depicts the sequence alignment between anti-BCMA mAb and comparator antibodies, where CDR regions are labeled with black boxes.DETAILED DESCRIPTIONIn the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.The present disclosure provides, among others, isolated antibodies, methods of making such antibodies, monoclonal and / or recombinant monospecific antibodies, multi-specific antibodies, antibody-drug conjugates and / or immuno-conjugates composed from such antibodies or antigen binding fragments, pharmaceutical compositions containing the antibodies, monoclonal and / or recombinant monospecific antibodies, multi-specific antibodies, antibody-drug conjugates and / or immuno-conjugates, the methods for making the antibodies and compositions, and the methods for treating cancer using the antibodies and compositions disclosed herein.The terms “a”, “an” and “the” as used herein are defined to mean “one or more” and include the plural unless the context is inappropriate.The terms “polypeptide”, “peptide”, and “protein”, as used herein, are interchangeable and are defined to mean a biomolecule composed of amino acids linked by a peptide bond.The term “antigen” refers to an entity or fragment thereof which can induce an immune response in an organism, particularly an animal, more particularly a mammal including a human. The term includes immunogens and regions thereof responsible for antigenicity or antigenic determinants.The terms “antigen- or epitope-binding portion or fragment”, “variable region”, “variable region sequence”, or “binding domain” refer to fragments of an antibody that are capable of binding to an antigen (such as BCMA in this application). The antigen-binding fragment (Fab) is a region (Fab region) on an antibody that binds to antigens. These fragments may be capable of the antigen-binding function and additional functions of the intact antibody. Examples of binding fragments include, but are not limited to, a single-chain Fv fragment (scFv) consisting of the variable light chain (VL) and variable heavy chain (VH) domains of a single arm of an antibody connected in a single polypeptide chain by aSIBA043PCT PATENTsynthetic linker, or a Fab fragment which is a monovalent fragment consisting of the VL, constant light (CL), VH and constant heavy 1 (CHI) domains.Antibody fragments can be even smaller sub-fragments and can consist of domains as small as a single CDR domain, in particular the CDR3 regions from either the VL and / or VH domains (for example see Beiboer et al., J. Mol. Biol. 296:833-49 (2000)). Antibody fragments are produced using conventional methods known to those skilled in the art. The antibody fragments can be screened for utility using the same techniques employed with intact antibodies.The “antigen- or epitope-binding portion or fragment”, “variable region”, “variable region sequence”, or “binding domain” may be derived from an antibody of the present disclosure by a number of art-known techniques. For example, purified monoclonal antibodies can be cleaved with an enzyme, such as pepsin, and subjected to HPLC gel filtration. Papain digestion of antibodies produces two identical antigen binding fragments, called “Fab” fragments, each with a single antigen binding site, and a residual “Fc” fragment, whose name reflects its ability to crystallize readily. Pepsin treatment yields an F(ab')2 fragment that has two antigen combining sites and is still capable of cross-linking antigen. The appropriate fraction containing Fab fragments can then be collected and concentrated by membrane filtration and the like. For further description of general techniques for the isolation of active fragments of antibodies, see for example, Khaw, B. A. et al. J. Nucl. Med. 23:1011-1019 (1982); Rousseaux et al. Methods Enzymology, 121:663-69, Academic Press, 1986.The term “antibody” is used in the broadest sense and specifically covers single monoclonal antibodies and / or recombinant antibodies (including agonist and antagonist antibodies), antibody compositions with poly epitopic specificity, as well as antibody fragments (e.g., Fab, F(ab')2, and Fv), so long as they exhibit the desired biological activity. In some embodiments, the antibody may be monoclonal, polyclonal, chimeric, single chain, multi-specific or multi -effective, human and humanized antibodies, as well as active fragments thereof. Examples of active fragments of molecules that bind to known antigens include Fab, F(ab')2, scFv and Fv fragments, including the products of a Fab immunoglobulin expression library and epitope-binding fragments of any of the antibodies and fragments mentioned above.The term “Fv” refers to the minimum antibody fragment which contains a complete antigen recognition and binding site. This region consists of a dimer of one heavy and one light chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRs of each variable domain interact to define an antigen binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.In some embodiments, antibody may include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e. molecules that contain a binding site and that immunospecifically bind an antigen. A typical antibody refers to heterotetrameric protein comprising typically of two heavy (H) chains and two light (L) chains. Each heavy chain is comprised of a heavy chain variable domain (abbreviated as VH) and a heavy chain constant domain. Each light chain is comprised of a light chain variable domain (abbreviated as VL) and a light chain constant domain. The light chains of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constantSIBA043PCT PATENTdomains. The VH and VL regions can be further subdivided into domains of hypervariable complementarity determining regions (CDR), and more conserved regions called framework regions (FR). Each variable domain (either VH or VL) is typically composed of three CDRs and four FRs, arranged in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4 from amino-terminus to carboxy-terminus. Within the variable regions of the light and heavy chains there are binding regions that interacts with the antigen.Depending on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM, and several of these may be further divided into subclasses (isotypes), e g., IgG-1, IgG-2, IgG-3, and IgG-4; IgA-1 and IgA-2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called alpha, delta, epsilon, gamma, and mu, respectively. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known.The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they are synthesized by the hybridoma culture, uncontaminated by other immunoglobulins. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present disclosure may be made by the hybridoma method first described by Kohler & Milstein, Nature, 256:495 (1975), or may be made by recombinant DNA methods (see, e g., U. S. Pat. No. 4,816,567). " Recombinant" means the antibodies are generated using recombinant nucleic acid techniques in exogeneous host cells.Monoclonal antibodies can be produced using various methods, including without limitation, mouse hybridoma, phage display, recombinant DNA, molecular cloning of antibodies directly from primary B cells, and antibody discovery methods (see Siegel. Transfus. Clin. Biol. 2002; Tiller. New Biotechnol. 2011; Seeber et al. PLOS One. 2014). Monoclonal antibodies may include “chimeric” antibodies (immunoglobulins) in which a portion of the heavy and / or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (U. S. Pat. No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Set. USA, 81:6851-6855

[1984] ).The term “humanized antibody” refers to a type of engineered antibody having its CDRs derived from a non-human donor immunoglobulin, the remaining immunoglobulin-derived parts of the molecule being derived from one (or more) human immunoglobulin(s). In addition, framework support residuesSIBA043PCT PATENTmay be altered to preserve binding affinity. Methods to obtain “humanized antibodies” are well known to those skilled in the art. (see, e.g., Queen et al., Proc. Natl Acad Sci USA, 86:10029-10032 (1989), Hodgson et al., Bio / Technology, 9:421 (1991)). Humanization of antibodies discovered in non-human species is a common practice not only to decrease the immunogenicity, but also to increase stability and remove sequence liabilities.The terms “isolated” or “purified” refers to a biological molecule free from at least some of the components with which it naturally occurs. Either “Isolated" or “purified," when used to describe the various polypeptides disclosed herein, means a polypeptide that has been identified and separated and / or recovered from a cell or cell culture from which it was expressed. Ordinarily, a purified polypeptide will be prepared by at least one purification step. An "isolated” or a “purified” antibody refers to an antibody which is substantially free of other antibodies having different antigenic a binding specificity.The term “immunogenic” refers to substances which elicit or enhance the production of antibodies, T-cells or other reactive immune cells directed against an immunogenic agent and contribute to an immune response in humans or animals. An immune response occurs when an individual produces sufficient antibodies, T-cells and other reactive immune cells against administered immunogenic compositions of the present disclosure to moderate or alleviate the disorder to be treated. While the immunogenic response generally includes both cellular (T cell) and humoral (antibody) arms of the immune response, antibodies directed against therapeutic proteins (anti-drug antibodies, ADA) may consist of IgM, IgG, IgE, and / or IgA isotypes.The terms "specific binding", "specifically binds to", or “is specific for a particular antigen or an epitope” means that the binding is measurably different from a non-specific interaction. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule, which generally is a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target.The term “affinity” refers to a measure of the attraction between two polypeptides, such as antibody / antigen, receptor / ligand, etc. The intrinsic attraction between two polypeptides can be expressed as the binding affinity equilibrium dissociation constant (KD) of a particular interaction. A KD binding affinity constant can be measured, e.g., by Bio-Layer Interferometry, where KD is the ratio of kdis (the dissociation rate constant) to kon (the association rate constant), as KD = kdis / kon.Specific binding for a particular antigen or an epitope can be exhibited, for example, by an antibody having a KD for an antigen or epitope of at least about 10-4 M, at least about 10-5 M, at least about 10-6 M, at least about 10-7 M, at least about 10-8 M, at least about 10-9 M, alternatively at least about 10-10 M, at least about 10-11 M, at least about 10-12 M, or greater, where KD refers to the equilibrium dissociation constant of a particular antibody-antigen interaction. Typically, an antibody that specifically binds an antigen will have a KD that is 20-, 50-, 100-, 500-, 1000-, 5,000-, 10,000- or more times greater for a control molecule relative to the antigen or epitope.Also, specific binding for a particular antigen or an epitope can be exhibited, for example, by an antibody having a KA or Ka for an antigen or epitope of at least 20-, 50-, 100-, 500-, 1000-, 5,000-, 10,000- or more times greater for the epitope relative to a control, where KA or Ka refers to an association rate of a particular antibody-antigen interaction.SIBA043PCT PATENTThe present disclosure may be understood more readily by reference to the following detailed description of specific embodiments and examples included herein. Although the present disclosure has been described with reference to specific details of certain embodiments thereof, it is not intended that such details should be regarded as limitations upon the scope of the disclosure.EXAMPLESExample 1. Generation of Anti-BCMA AntibodiesRabbit antibodies;Immunizations:For immunization, FreeStyle 293-F cells were transiently transfected with a eukaryotic expression vector (made in-house) encoding human (SEQ. ID No. 37 and 38), cynomolgus monkey (SEQ. ID No. 39 and 40), or mouse (SEQ. ID No. 41 and 42) BCMA. After 24 hours, cells were harvested and aliquoted for immunization. BCMA expression on transiently transfected cells was confirmed by flow cytometry using commercially available anti-BCMA mAbs (data not shown).Three cohorts were used for immunization, each with 2 rabbits. For Cohort 1, New Zealand White rabbits were immunized with IxlO6human BCMA-transfected cells in Complete Freund’s adjuvant. Rabbits were boosted every other week for 10 weeks. Each boost alternated cynomolgus, mouse, and human BCMA-transfected cells in Incomplete Freund’s adjuvant or CpG-2007 adjuvant. After the 5thimmunization, rabbits were immunized every 3 weeks in the same manner. Peripheral blood samples were collected at the 5th, 7th, 8th, 9th, 10th, and 11thimmunizations (Table 1). For cohort 2, New Zealand White rabbits were immunized using the same protocol, except Titermax adjuvant was used in place of Freund’s adjuvant (Table 1). Cohort 3 followed the same immunization protocol as Cohort 1 but used two b9 allotype rabbits instead of New Zealand White rabbits (Table 1).PBMC Isolation:Diluted blood at a 1:1 ratio, with DPBS, was layered onto 15mL of Lympholyte Cell Separation Media (Cedarlane, Cat. CL5050) in a 50mL tube. To obtain a layer of PBMCs, tubes were centrifuged at 2500rpm for 30 minutes at room temperature with no break. The white layer of PBMCs was then carefully removed and placed into a clean 50mL tube and diluted with DPBS to 50mL. Cells were then pelleted by centrifugation at 2500rpm for 10 minutes at room temperature with break. Any remaining red blood cells, RBCs, were then lysed by RBC lysis buffer (Qiagen, Cat. No. 158904). Briefly, cells were resuspended in 10mL of RBC lysis buffer and incubated at room temperature for 5 minutes. Lysis was then neutralized with 40mL of DPBS. Cells were pelleted again by centrifugation at 2500rpm for 10 minutes at room temperature. PBMCs were then prepared for storage by resuspending in 10% DMSO in FBS at a final concentration of <5 x 10A7 cells per ml.Three cohorts were used for immunization, each with 2 rabbits. For Cohort 1, New Zealand White rabbits were immunized with IxlO6human BCMA-transfected cells in Complete Freund’s adjuvant. Rabbits were boosted every other week for 10 weeks. Each boost alternated cynomolgus, mouse, and human BCMA-transfected cells in Incomplete Freund’s adjuvant or CpG-2007 adjuvant. After the 5th immunization, rabbits were immunized every 3 weeks in the same manner. Peripheral blood samples were collected at the 5th, 7th, 8th, 9th, 10th, and 11th immunizations (Table 1). For cohort 2, New Zealand White rabbits were immunized using the same protocol, except Titermax adjuvant was used in place of Freund’s adjuvant (Table 1). Cohort 3 followed the same immunization protocol as Cohort 1 but used two b9 allotype rabbits instead of New Zealand White rabbits (Table 1).SIBA043PCT PATENTIsolation of Rabbit PBMC from Whole Blood:Blood (~ 37 ml) was diluted 1:1 with DPBS (SH30028.02, Hyclone) and layered onto 15 ml of Lympholyte Cell Separation Media (Cedarlane, Cat. CL5050) in a 50 ml tube. Tubes were centrifuged at 2500 rpm for 30 minutes at RT with no break. Following centrifugation, the white PBMC layer was carefully aspirated, added to a clean tube, and diluted with DPBS to 50 ml. Cells were spun at 2500 rpm for 10 minutes at RT with high break. Cells were resuspended in 50 ml of DPBS, counted, and spun as described previously. Cell pellets were resuspended in 10% DMSO in FBS at a cell concentration of <5x107cells per ml.Isolation of rabbit B-cells by FACS:Immediately before sorting, 96-well culture plates were prepared using Immune Cell Media (ICM), rabbit splenocyte conditioned media (TSN), and irradiated EL4-B5 feeder cells. Immune Cell Media consisted of RPMI media (11875-093, Gibco) supplemented with FBS (Glutamax (35050-061, Gibco), HEPES (15630-080, Gibco), 2-Mercaptoethanol (21985-023, Gibco), and Penicillin / Streptomycin (2068818, Gibco). TSN was previously prepared in-house using rabbit splenocytes cultured with ICM and mitogens. EL4-B5 feeder cells were cultured and irradiated in-house. Optimal feeder cell number and TSN concentration was determined from large-scale batches well in advance of sorting. To make B-cell culture media, feeder cells were thawed, counted, and diluted in ICM containing TSN. B-cell culture media was added at 200 pl to each well of a 96-well U-bottom culture plate, and plates were stored at 37°C until sorting.Staining rabbit PBMC for FACS:PBMC were thawed in pre-warmed ICM, then incubated with a staining mix (100µl of staining mix per 1x10⁷ PBMC) containing 2 pg / ml anti-rabbit IgG-AF647 (111-606-046, Jackson ImmunoResearch), IgM-FITC (4020-02, Southern Biotech), IgA-FITC (AAI46F, Bio-Rad), CD8-FITC (MCA1576F, Bio-Rad), CD4-FITC (MCA799F, Bio-Rad), Human BCMA(AFR193-020, R& D Systems) conjugated to AF647, and Cynomolgus monkey BCMA (10029-BC-050, R& D Systems) conjugated to AF594. Following incubation, PBMC were washed and incubated with Anti-FITC microbeads (130-048-701, Miltenyi Biotec) diluted 1:4 in FACS buffer. FACS buffer consisted of DPBS supplemented with 1% FBS (SH30028.02, Seradigm) and EDTA (46-034-C1, Corning Cellgro). PBMC were passed through a QuadroMACS Separator magnet to remove IgM+, IgA+, CD8+, and CD4+ cells bound to anti-FITC microbeads. Flow through was collected, pelleted, and resuspended in efluor780 viability dye (65-0865-18, eBioscience) diluted 1:1000 in DPBS. Following incubation, cells were washed, resuspended in 4ml of FACS buffer, and stored at 4°C until sorting.Sorting of Rabbit B-Cells:To sort B-cells, the appropriate compensation was performed using both sorter software and manual adjustments. Gates were set up using the following strategy: Singlet gate (single cells) > Size gate (lymphocyte size) > Live cell gate (efluor780 negative) > IgG-positive / FITC- (IgM / IgA / CD8 / CD4) negative gate. B-cells were sorted from the final gate as single cells into 96-well u-bottom plates containing previously prepared B-cell culture media. Plates were incubated at 37°C with 5% CO2 for 12 days.Antibody screening by ELISA:B-cell cultures were screened for human BCMA binding by direct sandwich ELISA. High binding ELISA plates (3855, ThermoFisher) were coated with 100 pl of 1 pg / ml human BCMASIBA043PCT PATENT(AFR193-020, R& D Systems) diluted in DPBS. Plates were washed three times with 200 pl IX PBST (28352, ThermoFisher) using an automated plate washer (BioTek), then blocked with 100 pl of 2% BSA (BSA-30, Rockland Immunochemicals) in DPBS. B-cell clone supernatants were harvested from culture plates and stored for screening. B-cells remaining in the culture flask were stored in 80 pl of RNAlater (AM7021, ThermoFisher) at -80°C for RT-PCR amplification of antibody variable regions. After blocking, plates were washed as before and a 1:10 dilution of B-cell supernatant in blocking buffer was added to each plate. Following 1 hour incubation, plates were washed as before, then incubated with 100 pl of anti -Rabbit IgG secondary antibody conjugated to HRP diluted 1: 15000 in blocking buffer for 30 minutes. Plates were washed, then incubated for 15 minutes with 100 pl of TMB substrate (34029, ThermoFisher). Reactions were stopped by adding 100 pl of ELISA stop solution (SS04, ThermoFisher) and plates were read using a spectrophotometer at 450 nm. Detection of rabbit IgG antibodies specific to human BCMA were confirmed based off OD values exceeding the secondary only negative control (i.e., OD > 0.5). ELISA binding results are shown in Figure 1. Of 91 clones screened, 88% bound human BCMA and were selected for gene rescue.Example 2. Rabbit / Human Chimeric Monoclonal Antibodies;Amplification of Antibody Variable Regions:Multiplex RT-PCR:B-cell clones selected through ELISA screening were thawed from storage at -80°C. Primers specific to the leader sequence and constant region of the rabbit IgG and rabbit kappa sequences were used to amplify heavy and light chain variable sequences by multiplex RT-PCR. In a secondary PCR, amplicons were further amplified using nested primers containing restriction sites. Heavy chain and light chain amplicons were cloned into an expression vector containing human IgGl or human IgK, respectively. Sequence-verified expression plasmids were transiently co-transfected into 293 HEK cells for rabbit / human chimeric antibody production. As shown in Table 2, the disclosed rabbit clones were successfully amplified and expressed as chimeric antibodies (Table 2).Antibody screen by Flow Cytometry:Recombinant antibody supernatants were screened for binding to surface expressed BCMA by flow cytometry. 293 HEK cells were transiently transfected with eukaryotic expression vectors encoding human (SEQ. ID No. 69-70) or cynomolgus monkey (SEQ. ID No. 71-72) BCMA. 293 HEK cells transfected with irrelevant DNA were used as a negative control. Two days following transfection, cells were collected, stained with cell tracker dye (ThermoFisher Scientific, Cat. No. C34565), then stained with efluor780 viability dye (65-0865-18, eBioscience). Cells were combined, then plated at ~ 1.5x105 cells per well. Cells were incubated with chimeric antibodies serially diluted from 10 pg / ml to 0.04 pg / ml in FACS Buffer for 1 hour at 4°C. After incubation, cells were washed with FACS buffer, then incubated with 100 pl of Alexa Fluor 647 conjugated anti-rabbit IgG Fc secondary antibody (1:400 dilution, Jackson ImmunoResearch, Cat. No. 109-605-098) for 30 minutes at 4°C. After one wash, cells were resuspended in FACS buffer. Binding was determined by flow cytometry using a BD LSRFortessa flow cytometer. Figure 2 shows the binding of select chimeric antibodies to transfected 293 HEK. All three chimeric antibodies bound human BCMA with MFI values that fell within a similar range to the positive control mAb, SI-43C1 (Amgen Anti-BCMA clone, 2A1). Of the three clones, one antibody, 1343B4 bound cynomolgus monkey BCMA. None of the clones bound the negative control. Expression of the negative control DNA was confirmed using an antibody specific to the irrelevant protein.SIBA043PCT PATENTExample 3. Humanized Anti-BCMA AntibodiesHumanization of Heavy and Light Chain Variable Regions:The heavy and light chain variable regions of selected clones were humanized using the ‘Predict Humanizing Mutations’ algorithm in Discovery Studio. Methods chosen for humanization included best single mutation (BSM), frequent residue substitution (FRS), and FW 1.4. Resultant DNA sequences were cloned into mammalian expression vectors which express the human IgGl / kappa constant regions using gene fragments (Genewiz). Sequence-verified expression vectors were transiently co-transfected into 293 HEK cells for humanized antibody production. Antibody affinity screen by Bio-Layer Interferometry:Supernatants containing recombinant antibody were validated for binding to BCMA by bio-layer interferometry (also referred to in the patent as OCTET) using a ForteBio Octet Red 384 instrument. Antibodies were diluted to 10 pg / ml and captured onto Anti-human Fc biosensors. Antibody-coated sensors were associated with a 1:3 dilution series of His-tagged recombinant human (Aero Biosystems, Cat. No. BCA-H522y or produced in-house) or cynomolgus monkey BCMA extracellular domain (produced in-house) starting at 300nM. Following baseline establishment in kinetics buffer, the dissociation of BCMA from antibody was measured. Manufacturer-provided software was used to calculate curve fits and affinity.The OCTET binding activities of disclosed antibodies are shown in Figure 3. Humanized antibodies that bound recombinant human BCMA by bio-layer interferometry bound with high affinity at KD values within a 2 to 40 nM range (Figure 3A). The BSM humanization led to the highest affinities for clones 1343B4 and 1346F7. Humanization of 1346H10 eliminated binding. Humanized 1343B4 also bound recombinant cynomolgus monkey BCMA with KD values of- 13 nM (Figure 3B). Clone 1346F7 did not bind cynomolgus monkey BCMA. Control antibodies bound recombinant human BCMA by biolayer interferometry with KD values in 2 to 4 nM range (Figure 3C). Only SL43C1 (Amgen Anti-BCMA 2A1) bound cynomolgus monkey, with a KD value of - 40 nM. Overall, the disclosed antibodies bound human and cynomolgus BCMA at relatively equal levels; however, the KD value for 1343B4 BSM demonstrated higher affinity (see Table 3).Humanized antibodies - flow cytometry:Humanized antibody supernatants were screened for binding to surface expressed BCMA by flow cytometry as described previously. For the present screen, however, antibodies were expressed and screened in scFv format. As shown in Figure 4A, humanized 1343B4 BSM and FRS scFv demonstrated binding to both human and cynomolgus monkey BCMA. 1346H10 did not retain suitable binding after humanization. 1347F7 BSM and FRS scFv bound human BCMA, but not cynomolgus monkey BCMA. Binding to transfected cells was consistent with OCTET binding to recombinant protein. For comparison, control mAb SI-43C1 bound both human and cyno BCMA by flow cytometry (Figure 4B). SI-43C3 mAb bound only human BCMA, and the negative control mAb only bound the negative control transfected cells. Humanized anti-BCMA antibodies bound human BCMA levels at relatively equal EC50 levels to SI-43C3 (see Table 4).Cross-species binding to mouse and rat BCMA.Humanized anti-BCMA mAb 1343B4 FRS was analysed for cross-species binding to mouse (Aero Biosystems, Cat. No. BCA-R52H3) and rat (Aero Biosystems, Cat. No. BCA-M52H3) BCMA by OCTET using previously described methods. 1343B4 FRS bound human BCMA with an affinity of 0.6SIBA043PCT PATENTnM but did not bind mouse or rat BCMA. Control antibody, SI-43C4 (Janssen anti-BCMABCMB69) bound both mouse and rat BCMA with low affinity (Figure 5).Antibody Binning by Bio-Layer Interferometry (OCTET):The hierarchical clustering of disclosed humanized antibody 1343B4 FRS and positive control comparator antibodies are shown in the bin groups (Figure 6). Each square represents a separate bin. Dotted arrows between bins represent unidirectional blocking. 1343B4 FRS was bidirectionally blocked by SI-43C2 (GSK), SI-43C4 (Janssen), and SI-43C3 (SEAGEN), suggesting all antibodies bind at or near the same epitope on human BCMA. 1343B4 FRS was unidirectionally blocked by an Amgen antibody, suggesting partial epitope overlap: when bound to BCMA 1343B4FRS does not block SI-43C1 but is blocked by SI-43C1 when bound to BCMA. The overlap of epitopes between 1343B4 FRS and comparator antibodies can be expected due to the small size and structure of BCMA.Ligand Blocking by Bio-Layer Interferometry:BCMA binds two ligands, a proliferation inducing ligand (APRIL) and B-cell activating factor (BAFF). While APRIL and BAFF promote the survival of BCMA-expressing normal plasmablasts and bone marrow plasma cells, both ligands also demonstrate pro-survival factors for malignant plasma cells. To determine if the candidate clones block this interaction, humanized antibodies were validated for blocking APRIL:: BCMA binding by bio-layer interferometry. Biotinylated human BCMA (Aero Biosystems, Cat. No. BCA-H82E4) diluted to 300 nM was captured onto streptavidin-coated biosensors. Following baseline establishment in kinetics buffer, BCMA-coated sensors were then associated with candidate antibodies diluted to 10 pg / ml (i.e., Association #1). After Association #1, sensors were moved to wells containing 10 pg / ml APRIL-His (Aero Biosystems, Cat. No. APL-H52D1). Blocking of APRIL to antibody-bound BCMA was determine by the change in response from Association #1 to Association #2 relative to the positive and negative controls.As shown in Figure 7, humanized antibodies 1343B4 (BSM and FRS) and 1346F7 (BSM and FRS) blocked APRIL binding to human BCMA by bio-layer interferometry. Blocking with humanized 1346H10 antibodies could not be determined due to lack of BCMA binding. APRIL-His was also blocked in the presence of both control antibodies, SI-83 Cl and SI-83 C3.Internalization of anti-BCMA Antibodies and Lysosomal Trafficking:The mechanism of action for antibody-drug conjugate (ADC) drugs depends on internalization into cancer target-expressing tumor cells. Upon antibody binding, the cytotoxic payload is trafficked and released into cancer cell lysosomes, leading to cell death. The efficacy of cancer cell death can be attributed to several specific factors, including cancer target internalization, payload mechanism of action, and antibody binding. Clone 1343B4 and comparator antibodies were validated for internalization and lysosomal trafficking by flow cytometry. Controls included non-specific IgG (negative control) and anti-CD71 (positive control). Antibodies were labeled with 100 nM FabFluor-pH red. The fluorescent signal of FabFluor-pH red is dependent on low pH conditions and thus will allow the fluorescent quantification of labeled antibodies as they are internalized and trafficked into the acidic lysosome.Three BCMA-expressing cancer cell lines were used for this assay: MEC-1 (leukemia), RPMI-8226 (myeloma), and NCI-H929 (myeloma). Cells were thawed and cultured in RPMI media supplemented with Pen / Strep and 10% FBS. Cells were seeded at 10,000 cells / well in 96-well round bottom ULA plates (Corning). Antibodies were labeled with FabFluor-pH according to manufacturer’sSIBA043PCT PATENTinstructions. FabFlour-pH labeled antibodies and controls were added to plated cells at a final concentration of 10 nM. Cells were cultured for a maximum of 24 hours before flow cytometric acquisition using a BD LSRFortessa flow cytometer. Lysosomal trafficking was determined by calculation of the “Mean Adjusted Lysosomal Internalization Score”. Briefly, the geometric mean fluorescence intensity (gMFI) for each antibody and cell line was adjusted for background binding by subtracting the gMFI of the baseline control (non-specific IgG). The adjusted gMFI was then normalized to the maximum gMFI obtained for the given sample population. The final adjusted lysosomal internalization score was calculated by taking the mean value for each cell line. The results show that 1343B4 internalized and trafficked more efficiently than comparator anti-BCMA clones from Seagen and Janssen (Table 5).Sequence Alignment of Lead and Comparator Antibodies:Complementarity-determining regions (CDRs) for heavy and light chains were identified using the Kabat numbering scheme. CDR and framework sequences of 1343B4-FRS, 1347F7-FRS, 1346H10 and comparator antibodies were aligned using Geneious Prime bioinformatics software (Figure 8). As expected, framework regions shared up to 90% identity between comparator antibodies, 1343B4-FRS, 1347F7-FRS, and 1346H10. None of these alignments were significantly different. When the full variable regions were aligned, 1343B4-FRS shared 22-34% identity. In contrast, the % identities calculated between the CDRs of comparators alone ranged from 6-37%. When compared to comparator full variable regions, the % identity of 1343B4-FRS was significantly lower when compared to 2A1-Amgen or BCMB69-Janssen (P < 0.05). This highlighted the unique sequence characteristics of 1343B4-FRS, which can influence epitope binding and functional activity.Percent sequence identities were compared between 1343B4-FRS and comparators using a two-tailed, one-sample T-test. Briefly, the % identity of 1343B4-FRS to a given comparator antibody was compared to the average % identities of the remaining comparator antibodies. Comparisons were made across the entire variable region, CDRs only, and the framework region only. As expected, the percent identity of 1343B4-FRS framework and all other comparator antibodies was not significantly different (P > 0.05). However, when examining the full variable region or the CDRs, the % identity of 1343B4-FRS with 2A1 or BSMB69 was significantly lower than the average % identity of the comparators (P < 0.05). These differences may be attributed to the rabbit origin of 1343B4-FRS when compared to 2A1 or BSMB69. This unique characteristic can play a role in the structure of 1343B4-FRS, and therefore the uniqueness of the epitope which 1343B4-FRS binds to.Example 4. Comparative Advantages of Anti-BCMA Antibodies as TherapeuticsThe disclosure describes humanized rabbit monoclonal antibodies that target BCMA (1343B4, 1346H10, and 1346F7). 1343B4 is a high affinity antibody that binds human BCMA within nanomolar range. 1346F7 is a lower affinity antibody that binds human BCMA within low millimolar range. As a rabbit / human chimeric, 1346H10 bound human BCMA expressed on the surface of 293 HEK cells, but binding was lost following humanization. 1343B4 binds cynomolgus monkey BCMA, but not mouse or rat BCMA. By OCTET, the epitope of humanized 1343B4 FRS overlaps with comparator antibodies from Glaxo Smith Kline, Janssen, and Seattle Genetics. However, 1343B4 FRS demonstrated more efficient internalization and lysosomal trafficking when compared to the antibodies from Janssen and Seattle Genetics. Finally, binding of 1343B4 and 1347F7 to human BCMA blocks APRIL binding, suggesting that these clones can alter downstream functional activity.SIBA043PCT PATENTREFERENCES1. Paul, B. P., Rodriguez, C., & Usmani, S. Z. (2022). BCMA-targeted biologic therapies: the next standard of care multiple myeloma therapy. Drugs. 82(6): 613-631.https: / / www.ncbi.nlm.nih.gov / pmc / articles / PMC9554894 / pdf / nihms-1831629.pdf2. Sammartano, V., Franceschini, M., Fredduci, S., Caroni, F., Ciofini, S. Pacelli, & MB., Gozzetti, A. (2023). Anti-BCMA novel therapies for multiple myeloma. Cancer Drug Resistance.6:169-81. https: / / www.ncbi.nlm.nih.gov / pmc / articles / PMC10099603 / pdf / cdr-6-1-169.pdf3. Rees, M. J. & Kumar, S. (2023). BCMA-directed therapy, new treatments in the myeloma toolbox, and how to use them. Leukemia & Lymphoma.https: / / www.tandfonline.com / doi / full / 10.1080 / 10428194.2023.22840884. Lu, Q., Yang, D., Li H, Niu, T., & Tong, A. (2024). Multiple myeloma: signaling pathways and targeted therapy. 5:25. https: / / link.springer.com / content / pdf / 10.1186 / s43556-024-00188-w.pdf 5. Yu, B., Jiang, T., & Liu D. (2020). BCMA-target immunotherapy for multiple myeloma. Journal of Hematology & Oncology. 13:125.https: / / jhoonline.biomedcentral.com / articles / 10.1186 / s13045-020-00962-76. Moreaux, J., Legouffe, E., Jourdan, E., Quittet, P., Reme, T., Lugagne, C., et al. (2004). BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood. 103(8): 3148-3157. https: / / pubmed.ncbi.nIm.nih.gov / 15070697 / 7. Mohan, M., Sha, N., Luan, D., Mongem J., Forsberg, M., Bhatlapenumarthi, V, Balev, M., Patwari, A., et. Al. (2023). Teclistamab in relapsed refractory multiple myeloma: multi-institutional real-world study. 142: 545.https: / / ashpublications.org / blood / article / 142 / Supplement%201 / 545 / 502226 / Teclistamab-in-Relapsed-Refractory-Multiple8. Moreau, P., Garfall, A. L., W. C. J. van de Donk, N., Nahi, N., Usmani, S. (2022). Teclistamab in Relapsed or Refractory Multiple Myeloma. The New England Journal of Medicine. 387:495-505.https: / / www.nejm.org / doi / full / 10.1056 / NEJMoa22034789. Dimopoulos, M. A., Beksac, M., Pour, L., Delimpasi, S., Vorobyev, V., Quach, H., & Spicka, I. (2024). Belantamab mafodotin, pomalidomide, and dexamethasone in multiple myeloma. 391: 408-421. https: / / www.nejm.org / doi / full / 10.1056 / NEJMoa2403407SIBA043PCT PATENTTABLESTable 1. Immunization Protocol for Anti-BCMA Antibody Generation - Cohort 1, 2, and 3.Cohort-1, 3 Cohort-2 Day PostImmunogen Dose (jig)ImmunizationWholeAdjuvant Adjuvant Whole Bleed BleedHuman Complete0 IxlO Titerma BC A 2 36No x No M - 9 F Freund’sCynomolgus 6 Incomplete14 1x10 No CpG-2007 No BCMA-293F Freund’sMouse 6 Alum28 1x10 No Titermax No BCMA-293F CpG2007Human 6 Incomplete42 1x10 No CpG-2007 No BCMA-293F Freund’sCynomolgus Alum56 IxlO6Yes Titermax Yes BCMA-293F CpG2007Mouse Incomplete70 IxlO CpG-2007BC A 2 36No No M - 9 F Freund’sHuman 6 Alum91 1x10 Yes Titermax Yes BCMA-293F CpG2007Cynomolgus 6 Incomplete112 1x10 Yes CpG-2007 Yes BCMA-293F Freund’sMouse 6 Alum133 1x10 Yes Titermax Yes BCMA-293F CpG2007Human Incomplete154 IxlO6Yes CpG-2007 Yes BCMA-293F Freund’sCynomolgus 6 Alum175 1x10 Yes Titermax YesBCMA-293F CpG2007SIBA043PCT PATENTTable 2. Titer of rabbit / human chimeric mAbs.Rb / HuConcentrationChimeric(gg / ml)Clone Name1347F7 1171343B4 88.41346H10 45.3SIBA043PCT PATENTTable 3. Summary of OCTET affinities to human and cynomolgus monkey BCMA for humanized clones and controls.OCTET AffinityHuman BCMA Cyno BCMAClone Humanization KD (M) kon (1 / Ms) kdiss (1 / s) KD (M) kon (1 / Ms) kdiss (1 / s)BSM 2.13E-09 3.20E+05 6.81E-04 1.34E-08 5.11E+05 6.87E-03 1343B4 FRS 2.61E-09 3.67E+05 9.58E-04 1.30E-08 6.21E+05 8.08E-03FW1.4 N. B. N. B. N. B. N. T. N. T. N. T.BSM N. B. N. B. N. B. NT. N. T. N. T.1346H10 FRS N. B. N. B. N. B. N. T. N. T. N. T.FW1.4 N. B. N. B. N. B. N. T. N. T. N. T.BSM 1.08E-08 6.73E+05 7.23E-03 N. B. N. B. N. B.1347F7 FRS 3.89E-08 6.25E+05 2.43E-02 N. B. N. B. N. B.FW1.4 N. B. N. B. N. B. N. B. N. B. N. B.SI-43C1 (Amgen2.71E-09 4.03E+05 8.75E-04 3.96E-08 5.52E+05 2.18E-02 Anti-BCMA 2A1)SI-43C3 (Seagen3.65E-09 3.66E+05 1.34E-03 N. B. N. B. N. B.Anti-BCMA hSGl 6.17)Table 4. Summary of on-cell binding to human and cynomolgus monkey BCMA for humanized clones and controls.On-Cell BindingHuman BCMA Cyno BCMA Negative Control Clone Humanization Max MFI EC50 Max MFI EC50 Max MFI EC50 1343B4 BSM 4889 0.2411 4214 0.9463 N. B. N. B.FRS 5141 0.2966 4256 0.7919 N. B. N. B.1346H10 BSM 1175 47.38 N. B. N. B. N. B. N. B.FRS 1472 7.012 N. B. N. B. N. B. N. B.1347F7 BSM 3672 0.583 N. B. N. B. N. B. N. B.FRS 2068 2.967 N. B. N. B. N. B. N. B.SI-43C1 (Amgen5680 0.01464 3618 0.7933 N. B. N. B.Anti-BCMA 2A1)SI-43C3 (Seagen3572 0.3839 N. B. N. B. N. B. N. B.Anti-BCMA hSGl 6.17)SIBA043PCT PATENT Table 5A. The cell binding of anti-BCMA antibodies to human BCMA-expressing cell lines.Antibody RPMI-8226 MEC-1 NCI-929gMFI- gMFI- gMFI gMFI gMFI-IgG gMFIIgG IgGIgG (Negative Control) 694 0 133 0 604 0 Anti-CD71 (Positive Control) 8472 7778 1406 1273 1302 698 1343B4 (Rb / Hu Chimeric) 1350 656 229 96 1392 788 1343B4 (Humanized, FRS) 1457 763 211 78 1363 759 Seagen Anti-BCMA hSG16.17 1112 418 167 34 1109 542 Janssen Anti-BCMA BCMB69 1112 418 166 33 1146 479Table 5B. Summary of lysosomal internalization of 1343B4 and control from human BCMA-expressing cell lines.Adjusted Lysosomal Internalization Score Antibody RPMI-8226 MEC-1 NCI-929 MeanIgG (Negative Control)Anti-CD71 (Positive Control)1343B4 (Rb / Hu Chimeric) 0.86 1 1 0.953 1343B4 (Humanized, FRS) 1 0.81 0.96 0.925 Seagen Anti-BCMA hSG16.17 0.55 0.36 0.69 0.531 Janssen Anti-BCMA BCMB69 0.55 0.34 0.61 0.5SIBA043PCT PATENTSEQUENCE LISTINGLCVR HCVR LCVR HCVRProtein nucleotide nucleotide amino acid amino acidSeq ID Seq ID Seq ID Seq ID1343B4 1 2 3 41343B4FRS 5 6 7 81343B4 BSM 9 10 11 121343B4 FW1.4 13 14 15 161346H10 17 18 19 201346H10 FRS 41 32 36 441346H10 BSM 37 38 39 401346H10FW1.4 45 46 47 481347F7 21 22 23 241347F7 FRS 25 26 27 281347F7 BSM 29 30 31 321347F7 FW1.4 33 34 35 36LC HCProtein amino acid amino acidSeq ID Seq ID1343B4FRS 50 491343B4 BSM 53 541343B4 FW1.4 55 561346H10 FRS 59 601346H10 BSM 57 581346H10FW1.4 61 621347F7 FRS 63 641347F7 BSM 65 661347F7 FW1.4 67 68SIBA043PCT PATENTPlasmid / Domain Seq ID1343B4BSM scFv 751343B4FRS scFv 781346H10BSM scFv 761346H10FRS scFv 791347F7 BSM scFv 771347F7 FRS scFv 80Human IgGl amino acid 51Human CK amino acid 52Human BCMA nucleicacid 69Human BCMA amino acid 70Cyno BCMA nucleic acid 71Cyno BCMA amino acid 72Mouse BCMA nucleic acid 73Mouse BCMA amino acid 74Clone VH VLCDRH1 CDRH2 CDRH3 CDRL1 CDRL2 CDRL3 1343B4 81 82 83 84 85 86 1346H10 87 88 89 90 91 921347F7 93 94 95 96 97 98 *CDR regions in amino acid sequences are in bold> Seq ID 1: 1343B4 light chain variable region nucleic acid sequence GCCATCGAAATGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACC ATCAATTGCCAGGCCAGTGAGGACATTTATAGTTTATTGGCCTGGTATCAGCAGAAACCA GGGCAGCGTCCCAAGCTCCTGATCTATGGTGCATCCACTCTGGCATCTGGGGTCCCATCGC GGTTCAAAGGCAGTGGATCTGGGACAGAGTATACTCTCATCATCAGCGGCGTGCAGTGTG ACGATGCTGCCACTTACTTCTGTCAACGTGCTTATTATAGTAGTAAGACTGATATTGCTTT CGGCGGAGGCACCGAGGTGGAGTTCAAA> Seq ID 2: 1343B4 heavy chain variable region nucleic acid sequence CAGTCGCTGGAGGAGTCCGGGGGAGGCCTGGTCAAGCCTGGAGGAACCCTGACACTCAC CTGCTCAGCCTCTGGATACGACCCCAGTACCTACAGCATGTGTTGGGTCCGCCAGTCTCCA GGGAAGGGGCTGGAGTGGATCGCATGCATGAATAGTCGTGCTCCTAGTAGCACCTACCAC GCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTG CAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGCGGTCCTGCT GGTTGGGATGCTGATGGTTACTTTGGCTTGTGGGGCCCNGGGACCCTGGTCACCGTCTCGA GCSIBA043PCT PATENT> Seq ID 3: 1343B4 light chain variable region amino acid sequence AIEMTOTPSSVSAAVGGTVT1NCOASEDIYSLLAWYOQKPGORPKLL1YGASTLASGVPSRFK GSGSGTEYTLIISGVOCDDAATYFCQRAYYSSKTDIAFGGGTEVEFK> Seq ID 4: 1343B4 heavy chain variable region amino acid sequence OSLEESGGGLVKPGGTLTLTCSASGYDPSTYSMCWVROSPGKGLEWIACMNSRAPSSTYHA SWAKGRFTISKTSSTTVTLOMTSLTAADTATYFCASGPAGWDADGYFGLWGPGTLVTVSS> Seq ID 5: 1343B4 FRS light chain variable region nucleic acid sequence GACATCGTGATGACCCAGAGCCCCAGCAGCGTGAGCGCCAGCGTGGGCGACAGGGTGAC CATCAGCTGCCAGGCCAGCGAGGACATCTACAGCCTGCTGGCCTGGTACCAGCAGAAGCC CGGCCAGGCCCCCAAGCTGCTGATCTACGGCGCCAGCACCCTGGCCAGCGGCGTGCCCAG CAGGTTCAGCGGCAGCGGCAGCGGCACCGACTACACCCTGACCATCAGCAGCGTGCAGCC CGAGGACTTCGCCACCTACTACTGCCAGAGGGCCTACTACAGCAGCAAGACCGACATCGC CTTCGGCGGCGGCACCAAGGTGGAGATCAAG> Seq ID 6: 1343B4 FRS heavy chain variable region nucleic acid sequence CAGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGAAGCCCGGCGGCAGCCTGAGGCTGAG CTGCGCCGCCAGCGGCTACGACCCCAGCACCTACAGCATGTGCTGGGTGAGGCAGGCCCC CGGCAAGGGCCTGGAGTGGGTGGCCTGCATGAACAGCAGGGCCCCCAGCAGCACCTACC ACGCCAGCTGGGCCAAGGGCAGGTTCACCATCAGCAAGACCAGCAAGAACACCGTGTAC CTGCAGATGAACAGCCTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCAGCGGCCCC GCCGGCTGGGACGCCGACGGCTACTTCGGCCTGTGGGGCCAGGGCACCCTGGTGACCGTG AGCAGC> Seq ID 7: 1343B4 FRS light chain variable region amino acid sequenceDIVMTQSPSSVSASVGDRVTISCQASEDIYSLLAWYYQQKPGQAPKLLIYGASTLASGVPSRFSGSGSGTDYTLTISSVQPEDFATYYCQRAYYSSKTDIAFGGGTKVEIK> Seq ID 8: 1343B4 FRS heavy chain variable region amino acid sequence OQLVESGGGLVKPGGSLRLSCAASGYDPSTYSMCWVROAPGKGLEWVACMNSRAPSSTYH ASWAKGRFTISKTSKNTVYLOMNSLRAEDTAVYYCASGPAGWDADGYFGLWGOGTLVTV SS> Seq ID 9: 1343B4 BSM light chain variable region nucleic acid sequence GAGATCCAGATGACCCAGAGCCCCAGCAGCGTGAGCGCCACCGTGGGCCAGAGGGTGAC CATCACCTGCCAGGCCAGCGAGGACATCTACAGCCTGCTGGCCTGGTACCAGCAGAAGCC CGGCCAGAGGCCCAAGCTGCTGATCTACGGCGCCAGCACCCTGGCCAGCGGCGTGCCCAG CAGGTTCAAGGGCAGCGGCAGCGGCACCGACTACACCCTGATCATCAGCAGGGTGCAGA GCGACGACTTCGCCACCTACTACTGCCAGAGGGCCTACTACAGCAGCAAGACCGACATCG CCTTCGGCGGCGGCACCAGGGTGGAGATCAAGCAGSIBA043PCT PATENT> Seq ID 10: 1343B4 BSM heavy chain variable region nucleic acid sequence CAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGACCTG CAAGGCCAGCGGCTACGACCCCAGCACCTACAGCATGTGCTGGGTGAGGCAGCCCCCCGG CAAGGGCCTGGAGTGGATCGCCTGCATGAACAGCAGGGCCCCCAGCAGCACCTACCACG CCAGCTGGGCCAAGGGCAGGTTCACCATCAGCAAGACCAGCACCAACACCGTGTTCCTGC AGATGAGGAGCCTGAGGGCCGACGACACCGCCGTGTACTACTGCGCCAGCGGCCCCGCC GGCTGGGACGCCGACGGCTACTTCGGCCTGTGGGGCCCCGGCACCCTGGTGACCGTGAGC AGC> Seq ID 11: 1343B4 BSM light chain variable region amino acid sequence EIQMTQSPSSVSATVGQRVTITCQASEDIYSLLAWYQQKPGQRPKLLIYGASTLASGVPSRFKGSGSGTDYTLIISRVQSDDFATYYCQRAYYSSKTDIAFGGGTRVEIKQ> Seq ID 12: 1343B4 BSM heavy chain variable region amino acid sequence QLQESGGGLVQPGGSLRLTCKASGYDPSTYSMCWVRQPPGKGLEWIACMNSRAPSSTYHASWAKGRFTISKTSTNTVFLQMRSLRADDTAVYYCASGPAGWDADGYFGLWGPGTLVTVSS> Seq ID 13: 1343B4 FW1.4 light chain variable region nucleic acid sequence GAGATCGTGATGACCCAGAGCCCCAGCACCCTGAGCGCCAGCGTGGGCGACAGGGTGAT CATCACCTGCCAGGCCAGTGAGGACATTTATAGTTTATTGTGGTACCAGCAGAAGCCCGG CAAGGCCCCCAAGCTGCTGATCTACGGTGCATCCACTCTGGCATCTGGCGTGCCCAGCAG GTTCAGCGGCAGCGGCAGCGGCGCCGAGTTCACCCTGACCATCAGCAGCCTGCAGCCCGA CGACTTCGCCACCTACTACTGCGACGATGCTGCCACTTACTTCTGTCAACGTGCTTATTAT AGTAGTAAGACTGATATTGCTTTCGGCCAGGGCACCAAGCTGACCGTGCTGGGA> Seq ID 14: 1343B4 FW1.4 heavy chain variable region nucleic acid sequence TCAGAGGTGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAG GCTGAGCTGCACCGCCAGCGGATACGACCCCAGTACCTACAGCATGTGTTGGGTGAGGCA GGCCCCCGGCAAGGGCCTGGAGTGGGTGGGCTGCATGAATAGTCGTGCTCCTAGTAGCAC CTACCACGCGAGCTGGGCGAAAGGCAGGTTCACCATCAGCAGGGACACCAGCAAGAACA CCGTGTACCTGCAGATGAACAGCCTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCA GGGGTCCTGCTGGTTGGGATGCTGATGGTTACTTTGGCTTGTGGGGCCAGGGCACCCTGGT GACCGTGAGCAGC> Seq ID 15: 1343B4 FW1.4 light chain variable region amino acid sequence EIVMTQSPSTLSASVGDRVIITCQASEDIYSLLWYQQKPGKAPKLLIYGASTLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCDDAATYFCQRAYYSSKTDIAFGQGTKLTVLG> Seq ID 16: 1343B4 FW1.4 heavy chain variable region amino acid sequence OLVESGGGLVOPGGSLRLSCTASGYDPSTYSMCWVROAPGKGLEWVGCMNSRAPSSTYHA SWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARGPAGWDADGYFGLWGOGTLVTV SSSIBA043PCT PATENT> Seq ID 17: 1346H10 light chain variable region nucleic acid sequence GCTGACATTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTC ACCATCAAGTGCCAGGCCAGTCAGAGTATTAGAAGCTACTTAGCCTGGTATCAGCAGAAA CCAGGGCAGTCTCCCAAGCTCCTGATCTATGAAACATCCAAACTGGCCTCTGGGGTCCCA TCGCGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCGACCTGGAG TGTGCCGATGCTGCCACTTACTACTGTCAAACCTATTATTATAGTGATGGTCATAGTGATG GTGCTGCTTTCGGCGGGGGGACCGAGGTGGAGGTCAAA> Seq ID 18: 1346H10 heavy chain variable region nucleic acid sequence CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC TGCACAGCCTCTGGATTCTCCCTCAGTAGCTATGGAGTGAACTGGGTCCGCCAGGCTCCA GGGAAGGGGCTGGAGTGGATCGGATACATTTATCCTGATACTGGTAGAACATACTACGCG AGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTGGCCCTCAAAATC ACCAGTCCGACAACCGAGGACACGGCCACATATTTCTGTGCCAGAGGGGAGTATGGTGGT TATGGTGCTTGCGGTTTGTGGGGCCCAGGCATCCTCGTCACCGTCTCGAGC> Seq ID 19: 1346H10 light chain variable region amino acid sequence ADIVMTOTPASVEAAVGGTVTIKCOASOSIRSYLAWYQQKPGOSPKLLIYETSKLASGVPSRF SGSGSGTEFTLTISDLECADAATYYCQTYYYSDGHSDGAAFGGGTEVEVK> Seq ID 20: 1346H10 heavy chain variable region amino acid sequenceQSLEESGGRLVTPGTPLTLTCTASGFSLSSYGVNWVRQAPGKGLEWIGYIYPDTGRTYYASWAKGRFTISKTSTTVALKITSPTTEDTATYFCARGEYGGYGACGLWGPGILVTVSS> Seq ID 21: 1347F7 light chain variable region nucleic acid sequence GCCATCAAAATGACCCAGACTCCAGGCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACC ATCAACTGCCAGGCCAGTCAGAGCATTGGTACTAGGTTAGCCTGGTATCAACAGAAACCA GGGCAGCCTCCCAAGCTCCTGATCTACGATGCATCCAAACTGGCATCTGGGGTCTCATCG CGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGAGGCGTGCAGTGT GACGATGTTGCCACTTACTACTGTCTAGGTATTTGGGGTTATGGTGCCGATGATGGTGTTG CTTTCGGCGGAGGCACCGAGGTGGTGTTCAAA> Seq ID 22: 1347F7 heavy chain variable region nucleic acid sequence CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACC TGTACAGCCTCTGGATTCACCATCAGTACCTACCGCATGATCTGGGTCCGCCAGGCTCCAG GCGAGGGGCTGGAATACATCGGATTCATTGCTACTGATGGTACCACATACTACGCGAGCT GGGCAAAAGGCCGATTCACCATCTCCAGAACCTCGTCCACGGTGGATCTGAGAATGACCA GTCTGACAAGCGAAGACACGGCCACCTATTTCTGTGCCGGAGGGACATGGCATTATACCT CCGATATGGGGTACTACGTTGGCATCTGGGGCCCAGGCACCCTCGTCACCGTCTCGAGC> Seq ID 23: 1347F7 light chain variable region amino acid sequenceSIBA043PCT PATENTAIKMTQTPGSVSAAVGGTVTINCQASQSIGTRLAWYQQKPGQPPKLLIYDASKLASGVSSRFKGSGSGTEFTLTIRGVQCDDVATYYCLGIWGYGADDGVAFGGGTEVVFK> Seq ID 24: 1347F7 heavy chain variable region amino acid sequence QSVEESGGRLVTPGTPLTLTCTASGFTTSTYRMIWVRQAPGEGLEYIGFIATDGTTYYASWAKGRFTISRTSSTVDLRMTSLTSEDTATYFCAGGTWHYTSDMGYYVGIWGPGTLVTVSS> Seq ID 25: 1347F7 FRS light chain variable region nucleic acid sequence GACATCGTGATGACCCAGAGCCCCAGCAGCCTGAGCGCCAGCGTGGGCGACAGGGTGAC CATCAGCTGCCAGGCCAGCCAGAGCATCGGCACCAGGCTGGCCTGGTACCAGCAGAAGC CCGGCCAGGCCCCCAAGCTGCTGATCTACGACGCCAGCAAGCTGGCCAGCGGCGTGCCCA GCAGGTTCAGCGGCAGCGGCAGCGGCACCGAGTTCACCCTGACCATCAGCAGCGTGCAGC CCGACGACTTCGCCACCTACTACTGCCTGGGCATCTGGGGCTACGGCGCCGACGACGGCG TGGCCTTCGGCGGCGGCACCAAGGTGGAGATCAAG> Seq ID 26: 1347F7 FRS heavy chain variable region nucleic acid sequence CAGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGAAGCCCGGCGGCAGCCTGAGGCTGAG CTGCGCCGCCAGCGGCTTCACCATCAGCACCTACAGGATGATCTGGGTGAGGCAGGCCCC CGGCAAGGGCCTGGAGTGGGTGGGCTTCATCGCCACCGACGGCACCACCTACTACGCCAG CTGGGCCAAGGGCAGGTTCACCATCAGCAGGGACAAGAACACCGTGTACCTGCAGATGA ACAGCCTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCGGCGGCACCTGGCACTACA CCAGCGACATGGGCTACTACGTGGGCATCTGGGGCCAGGGCACCCTGGTGACCGTGAGCA GC> Seq ID 27: 1347F7 FRS light chain variable region amino acid sequence DIVMTQSPSSLSASVGDRVTISCQASQSIGTRLAWYQQKPGQAPKLLIYDASKLASGVPSRFSGSGSGTEFTLTISSVQPDDFATYYCLGIWGYGADDGVAFGGGTKVEIK> Seq ID 28: 1347F7 FRS heavy chain variable region amino acid sequence QQLVESGGGLVKPGGSLRLSCAASGFTISTYRMIWVRQAPGKGLEWVGFIATDGTTYYASWAKGRFTISRDKNTVYLQMNSLRAEDTAVYYCAGGTWHYTSDMGYYVGIWGQGTLVTVSS> Seq ID 29: 1347F7 BSM light chain variable region nucleic acid sequence GCCATCGTGATGACCCAGAGCCCCAGCACCCTGAGCGCCACCGTGGGCCAGAGGGTGACC ATCAGCTGCCAGGCCAGCCAGAGCATCGGCACCAGGCTGGCCTGGTACCAGCAGAAGCC CGGCAAGCCCCCCAAGCTGCTGATCTACGACGCCAGCAAGCTGGCCAGCGGCGTGCCCAG CAGGTTCAGCGGCAGCGGCAGCGGCACCGAGTTCACCCTGACCATCACCAGCGTGCAGAG CGACGACTTCGCCACCTACTACTGCCTGGGCATCTGGGGCTACGGCGCCGACGACGGCGT GGCCTTCGGCGGCGGCACCAGGGTGGACATCAAGCAG> Seq ID 30: 1347F7 BSM heavy chain variable region nucleic acid sequenceSIBA043PCT PATENTCAGCTGCTGGAGAGCGGCGGCAGGCTGGTGAAGCCCGGCACCACCCTGAGGCTGACCTG CAAGGCCAGCGGCTTCACCATCAGCACCTACAGGATGATCTGGGTGAGGCAGGCCCCCGG CCAGGGCCTGGAGTACATCGGCTTCATCGCCACCGACGGCACCACCTACTACGCCAGCTG GGCCAAGGGCAGGTTCACCATCAGCAGGACCACCAACACCGTGTTCCTGAGGATGAGGA GCCTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCGGCGGCACCTGGCACTACACCA GCGACATGGGCTACTACGTGGGCATCTGGGGCCCCGGCACCCTGGTGACCGTGAGCAGC> Seq ID 31: 1347F7 BSM light chain variable region amino acid sequenceAIVMTQSPSTLSATVGQRVTISCQASQSIGTRLAWYQQKPGKPPKLLIYDASKLASGVPSRFSGSGSGTEFTLTITSVQSDDFATYYCLGIWGYGADDGVAFGGGTRVDIKQ> Seq ID 32: 1347F7 BSM heavy chain variable region amino acid sequence QLLESGGRLVKPGTTLRLTCKASGFTISTYRMIWVRQAPGQGLEYIGFIATDGTTYYASWAKGRFTISRTTNTVFLRMRSLRAEDTAVYYCAGGTWHYTSDMGYYVGIWGPGTLVTVSS> Seq ID 33: 1347F7 FW1.4 light chain variable region nucleic acid sequence GAGATCGTGATGACCCAGAGCCCCAGCACCCTGAGCGCCAGCGTGGGCGACAGGGTGAT CATCACCTGCCAGGCCAGTCAGAGCATTGGTACTAGGTTAGCCTGGTACCAGCAGAAGCC CGGCAAGGCCCCCAAGCTGCTGATCTACGATGCATCCAAACTGGCATCTGGCGTGCCCAG CAGGTTCAGCGGCAGCGGCAGCGGCGCCGAGTTCACCCTGACCATCAGCAGCCTGCAGCC CGACGACTTCGCCACCTACTACTGCCTAGGTATTTGGGGTTATGGTGCCGATGATGGTGTT GCTTTCGGCCAGGGCACCAAGCTGACCGTGCTGGGA> Seq ID 34: 1347F7 FW1.4 heavy chain variable region nucleic acid sequence TCAGAGGTGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAG GCTGAGCTGCACCGCCAGCGGATTCACCATCAGTACCTACCGCATGATCTGGGTGAGGCA GGCCCCCGGCAAGGGCCTGGAGTGGGTGGGCTTCATTGCTACTGATGGTACCACATACTA CGCGAGCTGGGCAAAAGGCAGGTTCACCATCAGCAGGGACACCAGCAAGAACACCGTGT ACCTGCAGATGAACAGCCTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCAGGGGG ACATGGCATTATACCTCCGATATGGGGTACTACGTTGGCATCTGGGGCCAGGGCACCCTG GTGACCGTGAGCAGC> Seq ID 35: 1347F7 FW1.4 light chain variable region amino acid sequence EIVMTQSPSTLSASVGDRVIITCQASQSIGTRLAWYQQKPGKAPKLLIYDASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCLGIWGYGADDGVAFGQGTKLTVLG> Seq ID 36: 1347F7 FW1.4 heavy chain variable region amino acid sequence QLVESGGGLVQPGGSLRLSCTASGFTISTYRMIWVRQAPGKGLEWVGFIATDGTTYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARGTWHYTSDMGYYVGIWGQGTLVTVSS> Seq ID 37: 1346H10 BSM light chain variable region nucleic acid sequence GACATCGTGATGACCCAGAGCCCCAGCACCCTGAGCGCCACCGTGGGCCAGAGGGTGAC CATCACCTGCCAGGCCAGCCAGAGCATCAGGAGCTACCTGGCCTGGTACCAGCAGAAGCCSIBA043PCT PATENTCGGCAAGCCCCCCAAGCTGCTGATCTACGAGACCAGCAAGCTGGCCAGCGGCGTGCCCAG CAGGTTCAGCGGCAGCGGCAGCGGCACCGAGTTCACCCTGACCATCAGCAGCCTGCAGTG CGAGGACTTCGCCACCTACTACTGCCAGACCTACTACTACAGCGACGGCCACAGCGACGG CGCCGCCTTCGGCGGCGGCACCAGGGTGGAGATCAAG> Seq ID 38: 1346H10 BSM heavy chain variable region nucleic acid sequence CAGCAGCTGCTGGAGAGCGGCGGCAGGCTGGTGAAGCCCGGCGAGACCCTGAGGCTGAG CTGCAAGGCCAGCGGCTTCAGCCTGAGCAGCTACGGCGTGAACTGGGTGAGGCAGGCCCC CGGCAAGGGCCTGGAGTGGATCGGCTACATCTACCCCGACACCGGCAGGACCTACTACGC CAGCTGGGCCAAGGGCAGGTTCACCATCAGCAAGAGCACCAGCACCGTGTTCCTGCAGAT CAGGAGCCCCAGGACCGAGGACACCGCCATCTACTACTGCGCCAGGGGCGAGTACGGCG GCTACGGCGCCTGCGGCCTGTGGGGCCAGGGCATCCTGGTGACCGTGAGCAGC> Seq ID 39: 1346H10 BSM light chain variable region amino acid sequenceDIVMTQSPSTLSATVGQRVTITCQASQSIRSYLAWYQQKPGKPPKLLIYETSKLASGVPSRFSGSGSGTEFTLTISSLQCEDFATYYCQTYYYSDGHSDGAAFGGGTRVEIK> Seq ID 40: 1346H10 BSM heavy chain variable region amino acid sequence QQLLESGGRLVKPGETLRLSCKASGFSLSSYGVNWVRQAPGKGLEWIGYIYPDTGRTYYAS WAKGRFTISKSTSTVFLQIRSPRTEDTAIYYCARGEYGGYGACGLWGQGILVTVSS> Seq ID 41: 1346H10 FRS light chain variable region nucleic acid sequence GACATCGTGATGACCCAGAGCCCCAGCAGCCTGAGCGCCAGCGTGGGCGACAGGGTGAC CATCAGCTGCCAGGCCAGCCAGAGCATCAGGAGCTACCTGGCCTGGTACCAGCAGAAGCC CGGCCAGGCCCCCAAGCTGCTGATCTACGAGACCAGCAAGCTGGCCAGCGGCGTGCCCAG CAGGTTCAGCGGCAGCGGCAGCGGCACCGAGTTCACCCTGACCATCAGCAGCCTGGAGCC CGAGGACTTCGCCACCTACTACTGCCAGACCTACTACTACAGCGACGGCCACAGCGACGG CGCCGCCTTCGGCGGCGGCACCAAGGTGGAGATCAAG> Seq ID 42: 1346H10 FRS heavy chain variable region nucleic acid sequence CAGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGAAGCCCGGCGGCAGCCTGAGGCTGAG CTGCGCCGCCAGCGGCTTCAGCCTGAGCAGCTACGGCGTGAACTGGGTGAGGCAGGCCCC CGGCAAGGGCCTGGAGTGGGTGGGCTACATCTACCCCGACACCGGCAGGACCTACTACGC CAGCTGGGCCAAGGGCAGGTTCACCATCAGCAAGAGCAAGAACACCGTGTACCTGCAGA TGAACAGCCTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCAGGGGCGAGTACGGC GGCTACGGCGCCTGCGGCCTGTGGGGCCAGGGCACCCTGGTGACCGTGAGCAGC> Seq ID 43: 1346H10 FRS light chain variable region amino acid sequenceDIVMTQ SP S SLSASVGDRVTISCOASOSIRSYLAWYOQKPGOAPKLLIYETSKLASGVPSRF SG SGSGTEFTLTISSLEPEDFATYYCOTYYYSDGHSDGAAFGGGTKVEIK> Seq ID 44: 1346H10 FRS heavy chain variable region amino acid sequenceSIBA043PCT PATENTQQLVESGGGLVKPGGSLRLSCAASGFSLSSYGVNWVRQAPGKGLEWVGYIYPDTGRTYYASWAKGRFTISKSKNTVYLQMNSLRAEDTAVYYCARGEYGGYGACGLWGQGTLVTVSS> Seq ID 45: 1346H10 FW1.4 light chain variable region nucleic acid sequence GAGATCGTGATGACCCAGAGCCCCAGCACCCTGAGCGCCAGCGTGGGCGACAGGGTGAT CATCACCTGCCAGGCCAGTCAGAGTATTAGAAGCTACTTAGCCTGGTACCAGCAGAAGCC CGGCAAGGCCCCCAAGCTGCTGATCTACGAAACATCCAAACTGGCCTCTGGCGTGCCCAG CAGGTTCAGCGGCAGCGGCAGCGGCGCCGAGTTCACCCTGACCATCAGCAGCCTGCAGCC CGACGACTTCGCCACCTACTACTGCCAAACCTATTATTATAGTGATGGTCATAGTGATGGT GCTGCTTTCGGCCAGGGCACCAAGCTGACCGTGCTGGGA> Seq ID 46: 1346H10 FW1.4 heavy chain variable region nucleic acid sequence TCAGAGGTGCAGCTGGTGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAG GCTGAGCTGCACCGCCAGCGGATTCTCCCTCAGTAGCTATGGAGTGAACTGGGTGAGGCA GGCCCCCGGCAAGGGCCTGGAGTGGGTGGGCTACATTTATCCTGATACTGGTAGAACATA CTACGCGAGCTGGGCGAAAGGCAGGTTCACCATCAGCAGGGACACCAGCAAGAACACCG TGTACCTGCAGATGAACAGCCTGAGGGCCGAGGACACCGCCGTGTACTACTGCGCCAGGG GGGAGTATGGTGGTTATGGTGCTTGCGGTTTGTGGGGCCAGGGCACCCTGGTGACCGTGA GCAGC> Seq ID 47: 1346H10 FW1.4 light chain variable region amino acid sequence EIVMTQSPSTLSASVGDRVIITCQASQSIRSYLAWYQQKPGKAPKLLIYETSKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQTYYYSDGHSDGAAFGQGTKLTVLG> Seq ID 48: 1346H10 FW1.4 heavy chain variable region amino acid sequence EVQLVESGGGLVQPGGSLRLSCTASGFSLSSYGVNWVRQAPGKGLEWVGYIYPDTGRTYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARGEYGGYGACGLWGQGTLVTVSS> Seq ID 49: 1343B4 FRS heavy chain amino acid sequence QQLVESGGGLVKPGGSLRLSCAASGYDPSTYSMCWVRQAPGKGLEWVACMNSRAPSSTYHASWAKGRFTISKTSKNTVYLQMNSLRAEDTAVYYCASGPAGWDADGYFGLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPG> Seq ID 50: 1343B4 FRS light chain amino acid sequenceDIVMTQSPSSVSASVGDRVTISCQASEDIYSLLAWYYQQKPGQAPKLLIYGASTLASGVPSRFSGSGSGTDYTLTISSVQPEDFATYYCQRAYYSSKTDIAFGGGTKVEIKRTVAAPSVFIFPPSDEQSIBA043PCT PATENTLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY EKHKVYACEVTHQGLSSPVTKSFNRGEC> Seq ID 51: human IgGl amino acid sequence ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SL S S V VTVP S S SLGTQTYICNVNHKP SNTK VDKRVEPKSCDKTHTCPPCP APELLGGP S VFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPG> Seq ID 52: human CK amino acid sequence LTLSPVEALCDGRAQALMGDFAGVDFVFLVVCFAQRQGAAEAVGAVLAVLLCDTLLGVTRL EGVIHLPLYFGLSGIEVIQQAHNRGSSRFQLLIRWREDEDRWCSHRT> Seq ID 53: 1343B4 BSM light chain amino acid sequence EIQMTQSPSSVSATVGQRVTITCQASEDIYSLLAWYQQKPGQRPKLLIYGASTLASGVPSRFKGSGSGTDYTLIISRVQSDDFATYYCQRAYYSSKTDIAFGGGTRVEIKQLTLSPVEALCDGRAQALMGDFAGVDFVFLVVCFAQRQGAAEAVGAVLAVLLCDTLLGVTRLEGVIHLPLYFGLSGIEVIQQAHNRGSSRFQLLIRWREDEDRWCSHRT> Seq ID 54: 1343B4 BSM heavy chain amino acid sequence QLQESGGGLVQPGGSLRLTCKASGYDPSTYSMCWVRQPPGKGLEWIACMNSRAPSSTYHASWAKGRFTISKTSTNTVFLQMRSLRADDTAVYYCASGPAGWDADGYFGLWGPGTLVTVSSA STKGP S VFPL APS SK ST SGGTAALGCLVKD YFPEP VTVS WNSGALT SGVHTFP AVLQ S SGLYSL SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSD1AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL HNHYTQKSLSLSPG> Seq ID 55: 1343B4 FW1.4 light chain amino acid sequence EIVMTQSPSTLSASVGDRVIITCQASEDIYSLLWYQQKPGKAPKLLIYGASTLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCDDAATYFCQRAYYSSKTDIAFGQGTKLTVLGLTLSPVEAL CDGRAQALMGDFAGVDFVFLVVCFAQRQGAAEAVGAVLAVLLCDTLLGVTRLEGVIHLPLY FGLSGIEVIQQAHNRGSSRFQLLIRWREDEDRWCSHRT> Seq ID 56: 1343B4 FW1.4 heavy chain amino acid sequence QLVESGGGLVQPGGSLRLSCTASGYDPSTYSMCWVRQAPGKGLEWVGCMNSRAPSSTYHASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARGPAGWDADGYFGLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFSIBA043PCT PATENTPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPG> Seq ID 57: 1346H10 BSM light chain amino acid sequence DIVMTOSPSTLSATVGORVTITCOASOSIRSYLAWYOQKPGKPPKLLIYETSKLASGVPSRFSG SGSGTEFTLTISSLQCEDFATYYCQTYYYSDGHSDGAAFGGGTRVEIKLTLSPVEALCDGRAQ ALMGDFAGVDFVFLVVCFAQRQGAAEAVGAVLAVLLCDTLLGVTRLEGVIHLPLYFGLSGIE VIQQ AHNRGS SRFQLLIRWREDEDRWC SHRT> Seq ID 58: 1346H10 BSM heavy chain amino acid sequence OQLLESGGRLVKPGETLRLSCKASGFSLSSYGVNWVRQAPGKGLEWIGYIYPDTGRTYYAS WAKGRFTISKSTSTVFLQIRSPRTEDTAIYYCARGEYGGYGACGLWGQGILVTVSSASTKGPS VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPG> Seq ID 59: 1346H10 FRS light chain variable region amino acid sequenceDIVMTQ SP S SLS A S VGDR VTI SCQASQSTRSYLAW YQQKPGQ APKLLI YETSKLASGVP SRF SG SGSGTEFTLTISSLEPEDFATYYCQTYYYSDGHSDGAAFGGGTKVEIKLTLSPVEALCDGRAQ ALMGDFAGVDFVFLVVCFAQRQGAAEAVGAVLAVLLCDTLLGVTRLEGVIHLPLYFGLSGIE VIQQ AHNRGS SRFQLLIRWREDEDRWC SHRT> Seq ID 60: 1346H10 FRS heavy chain amino acid sequence QQLVESGGGLVKPGGSLRLSCAASGFSLSSYGVNWVRQAPGKGLEWVGYIYPDTGRTYYAS WAKGRFTISKSKNTVYLQMNSLRAEDTAVYYCARGEYGGYGACGLWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVP S S SLGTQTYICNVNHKP SNTKVDKRVEPK SCDKTHTCPPCP APELLGGP S VFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPG> Seq ID 61: 1346H10 FW1.4 light chain amino acid sequence EIVMTQSPSTLSASVGDRVIITCQASQSIRSYLAWYQQKPGKAPKLLIYETSKLASGVPSRFSG SGSGAEFTLTISSLQPDDFATYYCQTYYYSDGHSDGAAFGQGTKLTVLGASTKGPSVFPLAPS SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVSIBA043PCT PATENTTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD1AVEWES NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG> Seq ID 62: 1346H10 FW1.4 heavy chain amino acid sequence EVQLVESGGGLVQPGGSLRLSCTASGFSLSSYGVNWVRQAPGKGLEWVGYIYPDTGRTYYA SWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARGEYGGYGACGLWGQGTLVTVSSL TLSPVEALCDGRAQALMGDFAGVDFVFLVVCFAQRQGAAEAVGAVLAVLLCDTLLGVTRLE GVIHLPLYFGLSGIEVIQQAHNRGSSRFQLLIRWREDEDRWCSHRT> Seq ID 63: 1347F7 FRS light chain amino acid sequenceDIVMTQ SP S SLS AS VGDRVTI SCQASQSIGTRLAW YQQKPGQ APKLLIYDASKLASGVP SRF S GSGSGTEFTLTISSVOPDDFATYYCLGIWGYGADDGVAFGGGTKVEIKLTLSPVEALCDGRA QALMGDFAGVDFVFLVVCFAQRQGAAEAVGAVLAVLLCDTLLGVTRLEGVIHLPLYFGLSGI EVIQQ AHNRGS SRFQLLIRWREDEDRWC SHRT> Seq ID 64: 1347F7 FRS heavy chain amino acid sequence QQLVESGGGLVKPGGSLRLSCAASGFTISTYRMIWVRQAPGKGLEWVGFIATDGTTYYASW AKGRFTISRDKNTVYLQMNSLRAEDTAVYYCAGGTWHYTSDMGYYVGIWGOGTLVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SL S S V VTVP S S SLGTQTYICNVNHKP SNTK VDKRVEPKSCDKTHTCPPCPAPELLGGP S VFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPG> Seq ID 65: 1347F7 BSM light chain amino acid sequenceAIVMTQSPSTLSATVGQRVTISCQASQSIGTRLAWYQQKPGKPPKLLIYDASKLASGVPSRFS GSGSGTEFTLTITSVOSDDFATYYCLGIWGYGADDGVAFGGGTRVDIKQLTLSPVEALCDGR AQALMGDFAGVDFVFLVVCFAQRQGAAEAVGAVLAVLLCDTLLGVTRLEGVIHLPLYFGLS GSGIEVIQQAHNRGSSRFQLLIRWREDEDRWCSHRT> Seq ID 66: 1347F7 BSM heavy chain amino acid sequence QLLESGGRLVKPGTTLRLTCKASGFTISTYRMIWVRQAPGQGLEYIGFIATDGTTYYASWAK GRFTISRTTNTVFLRMRSLRAEDTAVYYCAGGTWHYTSDMGYYVGIWGPGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVP S S SLGTQTYICNVNHKP SNTKVDKRVEPK SCDKTHTCPPCP APELLGGP S VFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY P SDIAVEWESNGQPENNYKTTPP VLD SDGSFFL YSKLT VDKSRWQQGNVF SC S VMHEALHNH YTQKSLSLSPGSIBA043PCT PATENT> Seq ID 67: 1347F7 FW1.4 light chain amino acid sequence EIVMTQSPSTLSASVGDRVIITCQASQSIGTRLAWYQQKPGKAPKLLIYDASKLASGVPSRFSG SGSGAEFTLTISSLQPDDFATYYCLGIWGYGADDGVAFGQGTKLTVLGLTLSPVEALCDGRA QALMGDFAGVDFVFLVVCFAQRQGAAEAVGAVLAVLLCDTLLGVTRLEGVIHLPLYFGLSGI E VIQQ AHNRGS SRFQLLIRWREDEDRWC SHRT> Seq ID 68: 1347F7 FW1.4 heavy chain amino acid sequence QLVESGGGLVQPGGSLRLSCTASGFTISTYRMIWVRQAPGKGLEWVGFIATDGTTYYASWA KGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARGTWHYTSDMGYYVGIWGQGTLVTVSS ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY SL S S V VTVP S S SLGTQTYICNVNHKP SNTK VDKRVEPKSCDKTHTCPPCPAPELLGGP S VFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPG> Seq ID 69: human BCMA nucleic acid sequence ATGTTGCAGATGGCTGGGCAGTGCTCCCAAAATGAATATTTTGACAGTTTGTTGCATGCTT GCATACCTTGTCAACTTCGATGTTCTTCTAATACTCCTCCTCTAACATGTCAGCGTTATTGT AATGCAAGTGTGACCAATTCAGTGAAAGGAACGAATGCGATTCTCTGGACCTGTTTGGGA CTGAGCTTAATAATTTCTTTGGCAGTTTTCGTGCTAATGTTTTTGCTAAGGAAGATAAACT CTGAACCATTAAAGGACGAGTTTAAAAACACAGGATCAGGTCTCCTGGGCATGGCTAACA TTGACCTGGAAAAGAGCAGGACTGGTGATGAAATTATTCTTCCGAGAGGCCTCGAGTACA CGGTGGAAGAATGCACCTGTGAAGACTGCATCAAGAGCAAACCGAAGGTCGACTCTGAC CATTGCTTTCCACTCCCAGCTATGGAGGAAGGCGCAACCATTCTTGTCACCACGAAAACG AATGACTATTGCAAGAGCCTGCCAGCTGCTTTGAGTGCTACGGAGATAGAGAAATCAATT TCTGCTAGGTAA> Seq ID 70: human BCMA amino acid sequence MLQMAGQCSQNEYFDSLLHACIPCQLRCSSNTPPLTCQRYCNASVTNSVKGTNAILWTCLGLS LIISLAVFVLMFLLRKINSEPLKDEFKNTGSGLLGMANIDLEKSRTGDEIILPRGLEYTVEECTCE DCIKSKPKVDSDHCFPLPAMEEGATILVTTKTNDYCKSLPAALSATEIEKSISAR> Seq ID 71: cynomolgus monkey BCMA nucleic acid sequence ATGTTGCAGATGGCTCGGCAGTGCTCCCAAAATGAATATTTTGACAGTTTGTTGCATGATT GCAAACCTTGTCAACTTCGATGTTCTAGTACTCCTCCTCTAACATGTCAGCGTTATTGCAA TGCAAGTATGACCAATTCAGTGAAAGGAATGAATGCGATTCTCTGGACCTGTTTGGGACT GAGCTTGATAATTTCTTTGGCAGTTTTCGTGCTAACGTTTTTGCTAAGGAAGATGAGCTCT GAACCATTAAAGGATGAGTTTAAAAACACAGGATCAGGTCTCCTGGGCATGGCTAACATT GACCTGGAAAAGGGCAGGACTGGTGATGAAATTGTTCTTCCAAGAGGCCTGGAGTACACG GTGGAAGAATGCACCTGTGAAGACTGCATCAAGAATAAACCAAAGGTTGATTCTGACCATSIBA043PCT PATENTTGCTTTCCACTCCCAGCCATGGAGGAAGGCGCAACCATTCTCGTCACCACGAAAACGAAT GACTATTGCAATAGCCTGTCAGCTGCTTTGAGTGTTACGGAGATAGAGAAATCAATTTCTG CTAGGTAA> Seq ID 72: cynomolgus monkey BCMA amino acid sequence MLQMARQCSQNEYFDSLLHDCKPCQLRCSSTPPLTCQRYCNASMTNSVKGMNAILWTCLGL SLIISLAVFVLTFLLRKMSSEPLKDEFKNTGSGLLGMANIDLEKGRTGDEIVLPRGLEYTVEECT CEDCIKNKPKVDSDHCFPLPAMEEGATILVTTKTNDYCNSLSAALSVTEIEKSISAR> Seq ID 73: mouse BCMA nucleic acid sequence ATGGCGCAACAGTGTTTCCACAGTGAATATTTTGACAGTCTGCTGCATGCTTGCAAACCGT GTCACTTGCGATGTTCCAACCCTCCTGCAACCTGTCAGCCTTACTGTGATCCAAGCGTGAC CAGTTCAGTGAAAGGGACGTACACGGTGCTCTGGATCTTCTTGGGGCTGACCTTGGTCCTC TCTTTGGCACTTTTCACAATCTCATTCTTGCTGAGGAAGATGAACCCCGAGGCCCTGAAGG ACGAGCCTCAAAGCCCAGGTCAGCTTGACGGATCGGCTCAGCTGGACAAGGCCGACACC GAGCTGACTAGGATCAGGGCTGGTGACGACAGGATCTTTCCCCGAAGCCTGGAGTATACA GTGGAAGAGTGCACCTGTGAGGACTGTGTCAAGAGCAAACCCAAGGGGGATTCTGACCA TTTCTTCCCGCTTCCAGCCATGGAGGAGGGGGCAACCATTCTTGTCACCACAAAAACGGG TGACTACGGCAAGTCAAGTGTGCCAACTGCTTTGCAAAGTGTCATGGGGATGGAGAAGCC AACTCACACTAGATAA> Seq ID 74: mouse BCMA amino acid sequence MAQQCFHSEYFDSLLHACKPCHLRCSNPPATCQPYCDPSVTSSVKGTYTVLWIFLGLTLVLSL ALFTISFLLRKMNPEALKDEPQSPGQLDGSAQLDKADTELTRIRAGDDRIFPRSLEYTVEECTC EDCVKSKPKGDSDHFFPLPAMEEGATILVTTKTGDYGKSSVPTALQSVMGMEKPTHTR> Seq ID 75: 1343B4 BSM scFv amino acid sequence EIOMTOSPSSVSATVGORVTITCOASEDIYSLLAWYOQKPGORPKLLIYGASTLASGVPSRFK GSGSGTDYTLTIISRVQSDDFATYYCQRAYYSSKTDIAFGGGTRVEIКGGGGSGGGGSGGGGSG GGGSQQLQESGGGLVQPGGSLRLTCKASGYDPSTYSMCWVRQPPGKGLEWIACMNSRAPSS TYHASWAKGRFTISKTSTNTVFLQMRSLRADDTAVYYCASGPAGWDADGYFGLWGPGTLV TVSS> Seq ID 76: 1346H10 BSM scFv amino acid sequenceDIVMTQSPSTLSATVGQRVTITCQASQSIRSYLAWYQQKPGKPPKLLIУETSKLASGVPSRFSG SGSGTEFTLTISSLQCEDFATYYCQTYYYSDGHSDGAAFGGGTRVEIKGGGGSGGGGSGGGGSGGGGSQQLLESGGRLVKPGETLRLSCKASGFSLSSYGVNWVRQAPGKGLEWIGYIYPDTGRTYYASWAKGRFTISKSTSTVFLQIRSPRTEDTAIYYCARGEYGGYGACGLWGQGILVTVSS> Seq ID 77: 1347F7 BSM scFv amino acid sequenceAIVMTQSPSTLSATVGQRVTISCQASQSIGTRLAWYQQKPGKPPKLLIYDASKLASGVPSRFS GSGSGTEFTLTITSVQSDDFATYYCLGIWGYGADDGVAFGGGTRVDIKGGGGSGGGGSGGGSIBA043PCT PATENTGSGGGGSOOLLESGGRLVKPGTTLRLTCKASGFTISTYRMIWVRQAPGOGLEYIGFIATDGTT YYASWAKGRFT1SRTTNTVFLRMRSLRAEDTAVYYCAGGTWHYTSDMGYYVGIWGPGTLV TVSS> Seq ID 78: 1343B4 FRS scFv amino acid sequenceDIVMTQ SP S S VS AS VGDRVTISCQASEDIYSLLAWYQQKPGO APKLLIYGASTLASGVP SRF S GSGSGTDYTLTISSVQPEDFATYYCQRAYYSSKTDIAFGGGTKVEIKGGGGSGGGGSGGGGS GGGGSQOLVESGGGLVKPGGSLRLSCAASGYDPSTYSMCWVRQAPGKGLEWVACMNSRAP SSTYHASWAKGRFTISKTSKNTVYLQMNSLRAEDTAVYYCASGPAGWDADGYFGLWGOG TLVTVSS> Seq ID 79: 1346H10 FRS scFv amino acid sequenceDIVMTQSPSSLSASVGDRVTISCQASQSIRSYLAWYQQKPGQAPKLLIYETSKLASGVPSRFSG SGSGTEFTLTISSLEPEDFATYYCQTYYYSDGHSDGAAFGGGTKVEIKGGGGSGGGGSGGGG SGGGGSOOLVESGGGLVKPGGSLRLSCAASGFSLSSYGVNWVROAPGKGLEWVGYIYPDTG RTYYASWAKGRFTISKSKNTVYLOMNSLRAEDTAVYYCARGEYGGYGACGLWGOGTLVTvss> Seq ID 80: 1347F7 FRS scFv amino acid sequence DIVMTQSPSSLSASVGDRVTISCQASQSIGTRLAWYQQKPGQAPKLLIYDASKLASGVPSRFS GSGSGTEFTLTISSVOPDDFATYYCLGIWGYGADDGVAFGGGTKVEIKGGGGSGGGGSGGG GSGGGGSOQLVESGGGLVKPGGSLRLSCAASGFTISTYRMIWVROAPGKGLEWVGFIATDG TTYYASWAKGRFTI SRDKNT VYLQMNSLR AEDT A VYYC AGGTWHYTSDMGYYVGIWGQ GTLVTVSS> Seq ID 81: 1343B4 VH-CDRH1TYSMC> Seq ID 82: 1343B4 VH-CDRH2CMNSRAPS STYHASWAKG> Seq ID 83: 1343B4 VH-CDRH3GPAGWDADGYFGL> Seq ID 84: 1343B4 VL-CDRL1QASEDIYSLLA> Seq ID 85: 1343B4 VL-CDRL2GASTLAS> Seq ID 86: 1343B4 VL-CDRL3QRAYYSSKTDIASIBA043PCT PATENT> Seq ID 87: 1346H10 VH-CDRH1SYGVN> Seq ID 88: 1346H10 VH-CDRH2YIYPDTGRTYYASWAKG> Seq ID 89: 1346H10 VH-CDRH3GEYGGYGACGL> Seq ID 90: 1346H10 VL-CDRL1QASQSIRSYLA> Seq ID 91: 1346H10 VL-CDRL2ETSKLAS> Seq ID 92: 1346H10 VL-CDRL3QTYYYSDGHSDGAA> Seq ID 93: 1347F7 VH-CDRH1TYRMI> Seq ID 94: 1347F7 VH-CDRH2FIATDGTTYYASWAKG> Seq ID 95: 1347F7 VH-CDRH3GTWHYTSDMGYYVGI> Seq ID 96: 1347F7 VL-CDRL1QASQSIGTRLA> Seq ID 97: 1347F7 VL-CDRL2DASKLAS> Seq ID 98: 1347F7 VL-CDRL3LGIWGYGADDGVA

Claims

1. SIBA043PCT PATENTANTI-BCMA ANTIBODY AND METHOD OF MAKING AND USING THEREOFCLAIMSWhat is claimed is:

1. A B cell maturation antigen (BCMA) binding peptide having a binding specificity to human BCMA, comprisinga variable heavy (VH) chain having complementarity determining region (CDR) Hl, CDR H2, and CDR H3 ofSEQ ID NO 81, 82, and 83;SEQ ID NO 87, 88, and 89; orSEQ ID NO 93, 94, and 95; anda variable light (VL) chain having CDR LI, CDR L2, and CDR L3 ofSEQ ID NO: 84, 85, and 86;SEQ ID NO: 90, 91, and 92; orSEQ ID NO: 96, 97, and 98.

2. The BCMA binding peptide of Claim 1, comprising:the VH chain having the (CDR) Hl, CDR H2, and CDR H3 of SEQ ID NO: 81, 82, and 83; and the VL chain having CDR LI, CDR L2, and CDR L3 of SEQ ID NO: 84, 85, and 86, the VH chain having the (CDR) Hl, CDR H2, and CDR H3 of SEQ ID NO: 87, 88, and 89; and the VL chain having CDR LI, CDR L2, and CDR L3 of SEQ ID NO: 90, 91, and 92, or the VH chain having the (CDR) Hl, CDR H2, and CDR H3 of SEQ ID NO: 93, 94, and 95; and the VL chain having CDR LI, CDR L2, and CDR L3 of SEQ ID NO: 96, 97, and 98.

3. The BCMA binding peptide of Claim 1, wherein the VH chain comprises an amino acid sequence having at least 98%, 95%, or 92% sequence identity to SEQ ID NO. 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 49, 54, 56, 58, 60, 62, 64, 66, 68; and wherein the VL chain comprises an amino acid sequence having at least 98%, 95%, or 92% sequence identity to SEQ ID NO. 3, 7, 11, 15, 19, 23, 27, 31, 35, 36, 39, 47, 50, 53, 55, 57, 59, 61, 63, 65, 67.

4. The BCMA binding peptide of Claim 1, comprising a scFv domain or a Fab region having the binding specificity to BCMA.

5. The BCMA binding peptide of Claim 4, wherein the scFv domain comprises an amino acid sequence having at least 98%, 95%, or 92% sequence identity to SEQ ID NO. 75, 76, 77, 78, 79, or 80.

6. The BCMA binding peptide of Claim 4, wherein the scFv domain comprises a histidine residue linked to at least one end of the scFv domain.SIBA043PCT PATENT7. The BCMA binding peptide of Claim 4, wherein the Fab region comprises the VH having at least 98%, 95%, or 92% of sequence identity to SEQ ID NO: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, or 48, and the VL having at least 98%, 95%, or 92% of sequence identity to 3, 7, 11, 15, 19, 23, 27, 31, 35, 36, 39, or 47.

8. The BCMA binding peptide of Claim 4, wherein the Fab region is linked to a Fc domain to provide a Fab-monoFc fusion protein, wherein the Fc domain comprises an amino acid sequence having at least 98% sequence identity to SEQ ID NO: 51.

9. The BCMA binding peptide of Claim 4, wherein the Fab region is linked to a kappa light chain, wherein the kappa light chain comprises an amino acid sequence having at least 98% sequence identity to SEQ ID NO: 52.

10. An isolated monoclonal antibody (mAb), comprising the BCMA binding peptide of Claim 1.

11. The isolated mAb of Claim 10, comprising an amino acid sequence having at least 98%, 95%, or 92% of sequence identity to SEQ ID NO: 3, 4, 7, 8, 11, 12, 15, 16, 19, 20, 23, 24, 27, 28, 31, 32, 35, 36, 39, 40, 44, 47, 48, 49, 50, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 75, 76, 77, 78, 79, or 80.

12. The isolated mAb of Claim 10, comprising a light chain (LC) having an amino acid sequence having at least 98%, 95%, or 92% of sequence identity to SEQ ID NO: 50, 53, 55, 57, 59, 61, 63, 65, or 67.

13. The isolated mAb of Claim 10, comprising a heavy chain (HC) having an amino acid sequence having at least 98%, 95%, or 92% of sequence identity to SEQ ID NO: 49, 54, 56, 58, 60, 62, 64, 66, or 68.

14. The isolated mAb of Claim 10, further comprising a human framework region.

15. The isolated mAb of Claim 10, wherein the isolated mAb is a humanized antibody, a chimeric antibody, or a recombinant antibody.

16. The isolated mAb of Claim 10, wherein the isolated mAb is an IgG.

17. The isolated mAb of Claim 10, wherein the isolated mAb is a bispecific antibody, tri-specific antibody, or multi-specific antibody.

18. The isolated mAb of Claim 10, comprising an IgGl heavy chain having an amino acid sequence having at least 90% identity with the SEQ ID NO: 51.SIBA043PCT PATENT19. The isolated mAb of Claim 10, comprising a kappa light chain having an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 52.

20. The isolated mAb of Claim 10, comprising a variable heavy chain (VH) having an amino acid sequence having at least 90% identity with the SEQ ID NO: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 49, 54, 56, 58, 60, 62, 64, 66, or 68, and a variable light chain (VL) having an amino acid sequence having at least 90% identity with the SEQ ID NO: 3, 7, 11, 15, 19, 23, 27, 31, 35, 36, 39, 47, 50, 53, 55, 57, 59, 61, 63, 65, or 67.

21. The isolated mAb of Claim 10, comprising a scFv domain having the binding affinity to human BCMA, wherein the scFv domain comprises an amino acid sequence having at least 90% identity with the SEQ ID NO: 75, 76, 77, 78, 79, or 80.

22. An isolated nucleic acid encoding the BCMA binding peptide of Claim 1 or the isolated mAb of Claim 10.

23. An expression vector comprising the isolated nucleic acid sequences of Claim 22, wherein the expression vector is expressible in a cell.

24. A host cell comprising the nucleic acid of Claim 22, wherein the host cell is a prokaryotic cell or a eukaryotic cell.

25. A method of producing an isolated mAb of Claim 10, comprising culturing the host cell of one of Claim 24, so that the antibody is produced.

26. An immuno-conjugate, comprising the BCMA binding peptide of Claim 1 or the isolated mAb of Claim 10 conjugated to a drug unit through a linker, wherein the linker comprises a covalent bond selected from an ester bond, an ether bond, an amine bond, an amide bond, a disulfide bond, an imide bond, a sulfone bond, a phosphate bond, a phosphorus ester bond, a peptide bond, a hydrazone bond or a combination thereof.

27. The immuno-conjugate according to Claim 26, wherein the drug unit comprises a cytotoxic agent, an immune regulatory reagent, or a combination thereof.

28. The immuno-conjugate according to Claim 26, wherein the cytotoxic agent is selected from a growth inhibitory agent or a chemotherapeutic agent from a class of tubulin binders, DNA intercalators, DNA alkylators, enzyme inhibitors, immune modulators, antimetabolite agents, radioactive isotopes, or a combination thereof.SIBA043PCT PATENT29. The immuno-conjugate according to Claim 26, wherein the cytotoxic agent is selected from a calicheamicin, ozogamicin, monomethyl auristatin E, emtansinea derivative or a combination thereof.

30. The immuno-conjugate according to Claim 26, wherein the immune regulatory reagents activate or suppress immune cells, T cell, NK cell, B cell, macrophage, or dendritic cell.

31. A pharmaceutical composition, comprising the BCMA binding peptide of Claim 1, the isolated mAb antibody of Claim 10, or the immunoconjugate of Claim 26, and optionally a pharmaceutically acceptable carrier.

32. The pharmaceutical composition of Claim 31, further comprising a radioisotope, a radionuclide, a toxin, a therapeutic agent, a chemotherapeutic agent or a combination thereof.

33. The pharmaceutical composition of Claim 32, wherein the therapeutic agent comprises an anti-estrogen agent, a receptor tyrosine kinase inhibitor, a kinase inhibitor, a cell cycle inhibitor, a DNA, RNA or protein synthesis inhibitor, a RAS inhibitor, or a combination thereof.

34. A pharmaceutical composition comprising the BCMA binding peptide of Claim 1, the isolated mAb antibody of Claim 10, or the immunoconjugate of Claim 26 for use in a method for treating or preventing a cancer, an autoimmune disease, or an infectious disease in a subject, said method comprising administering to the subject said pharmaceutical composition.

35. A method of treating a subject with a cancer, comprising administering to the subject an effective amount of the BCMA binding peptide of Claim 1, the isolated mAb antibody of Claim 10, or the immunoconjugate of Claim 26.

36. The method of Claim 35, wherein the cancer comprises cells expressing BCMA.

37. The method of Claim 35, wherein the cancer comprises colorectal cancer, pancreatic cancer, esophageal cancer, nasopharyngeal cancer, anal cancer, rectal cancer, gastric cancer, or bladder cancer.

38. The method of Claim 35, further comprising co-administering an effective amount of a therapeutic agent.

39. The method of Claim 38, wherein the therapeutic agent comprises an antibody, a chemotherapy agent, an enzyme, an anti-estrogen agent, a receptor tyrosine kinase inhibitor, a kinase inhibitor, a cell cycle inhibitor, a DNA, RNA or protein synthesis inhibitor, a RAS inhibitor or a combination thereof.SIBA043PCT PATENT40. The method of Claim 35, wherein the subject is a human.

41. A solution comprising an effective concentration of the BCMA binding peptide of Claim 1, the isolated mAb of Claim 10, or the immunoconjugate of Claim 26, wherein the solution is blood plasma in a subject.

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