Patent Publication Number: US-2022218824-A1

Title: Multi-specific antibodies for cross-neutralization of multiple filovirus glycoproteins

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation-in-part of PCT International Application No. PCT/US201557499, filed Oct. 27, 2015, which claims benefit of U.S. Provisional Application Nos. 62/131,472, filed Mar. 11, 2015 and 62/069,516, filed Oct. 28, 2014, the contents of each of which are hereby incorporated by reference. 
    
    
     STATEMENT OF GOVERNMENT SUPPORT 
     This invention was made with government support under grant numbers AI009762 and AI090249 and GM007482 awarded by the National Institutes of Health. The government has certain rights in the invention. 
    
    
     BACKGROUND OF THE INVENTION 
     Throughout this application various publications are referred to in parentheses. Full citations for these references may be found at the end of the specification. The disclosures of these publications, and all patents, patent application publications and books referred to herein, are hereby incorporated by reference in their entirety into the subject application to more fully describe the art to which the subject invention pertains. 
     Ebola virus is an NIAID Category A biodefense pathogen that causes severe and rapidly progressing hemorrhagic fever with human case fatalities of 50-90%. There are currently no FDA-approved vaccines or therapies for Ebola virus infection. Among the five species of Ebola virus, the Zaire and Sudan variants (EBOV and SUDV, respectively) are the most pathogenic and both have resulted in recurring outbreaks. Together. EBOV and SUDV account for over 95% of EBOV-related deaths reported to date. 
     Herein are disclosed multi-specific antibodies for cross-neutralization of multiple filovirus glycoproteins. 
     SUMMARY OF THE INVENTION 
     This invention provides a composition comprising (1) a first single chain variable fragment (scFv) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a first species of filovirus, which first scFv is covalently joined to (2) a first polypeptide of an immunoglobulin G (IgG) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a second species of filovirus, wherein the first species of filovirus and second species of filovirus are different species. 
     A composition is also provided comprising (i) a first single chain variable fragment (scFv) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a first species of filovirus, which first scFv is covalently joined to (ii) a first polypeptide of an immunoglobulin G (IgG) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a second species of filovirus, the IgG having covalently joined thereto, at a different location from the attachment of (i) thereto, (iii) a second single chain variable fragment (scFv) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a third species of filovirus, wherein the first species of filovirus and second species of filovirus and third species of filovirus are all different species. In an embodiment, one species-specific scFv is fused to the light chain of an IgG, and different species-specific scFv is fused to the heavy chain of the IgG. 
     Also provided is an isolated nucleic acid encoding any of the compositions described herein. 
     Also provided is a method of treating a filovirus infection in a subject comprising administering an amount of a bispecific composition described herein to the subject effective to treat a filovirus infection in a subject. 
     Also provided is a method of preventing a filovirus infection in a subject comprising administering an amount of a bispecific composition described herein to the subject effective to inhibit a filovirus infection in a subject. 
     Also provided is a method of preventing a filovirus infection of a mammalian cell comprising contacting the filovirus with an amount of a bispecific composition described herein effective to inhibit a filovirus infection of a mammalian cell. 
     Also provided is a method of treating a filovirus infection in a subject comprising administering an amount of a trispecific composition described herein to the subject effective to treat a filovirus infection in a subject. 
     Also provided is a method of preventing a filovirus infection in a subject comprising administering an amount of a trispecific composition described herein to the subject effective to inhibit a filovirus infection in a subject. 
     Also provided is a method of preventing a filovirus infection of a mammalian cell comprising contacting the filovirus with an amount of a trispecific composition described herein effective to inhibit a filovirus infection of a mammalian cell. 
     Herein are disclosed cross-neutralizing, bispecific monoclonal antibody constructs against Ebola variants such as EBOV and SUDV. Recent structural studies indicate that the base of the envelope glycoprotein (GP) is susceptible to neutralization by antibodies in these two species. However, current EBOV and SUDV antibodies targeting this region are narrowly strain specific and therefore have limited therapeutic utility. Herein a fusion approach is disclosed whereby, for example, the IgG of one species-specific antibody (e.g., SUDV) is genetically fused to the scFv of another species-specific antibody (e.g., EBOV) to create a cross-species neutralizing antibody (or vice versa). This strategy can also be extended to generate trispecific antibody constructs. Antibody therapies against Ebolaviruses and other filoviruses have demonstrated post-exposure efficacy in nonhuman primates, but no cross-neutralizing antibodies exist. Therefore, the cross-neutralizing, bispecific antibodies disclosed herein fill a much needed gap in Ebola therapeutics. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A-18B : Structure of the prefusion GP1-GP2 spike and GP conformational changes that lead to viral membrane fusion (A) Structure of the GP1-GP2 spike ectodomain (PDB ID: 3CSY, (13)). The GP1 subunits are shown in surface-shaded view and GP2 as rods and loops. One GP1 subunit is colored to show the subdomains: b, base; h, head; gc, glycan cap, fp, fusion peptide; TM, transmembrane domain. C, GP C-terminus. (B) Membrane fusion-associated conformational rearrangements in GP2 inferred from its pre-fusion and putative post-fusion structures (PDB ID: 1EBO, ref. 17) 
         FIG. 2 . Survival of NHPs administered EBOV-specific serum IgGs upon viral challenge. Animals 7, 8, and 9 survived but the control animal (5) died 8-days post-exposure. (These data are from ref 21, Dye et al.). 
         FIG. 3 . Head-to-head comparison of KZ52 IgG vs. VSV-GP EBOV  and 16F6 IgG vs. VSV-GP SUDV . 
         FIG. 4 . Exemplary Bispecific (E10 &amp; F4 IgG+KZ52 scFv) designs. 
         FIG. 5 . Bispecifics (E10 &amp; F4 IgG+KZ52 scFv) SDS PAGE. 
         FIG. 6 . Bispecifics (F4 IgG+KZ52 scFv) binding data. 
         FIG. 7 . Bispecifics (E10 IgG+KZ52 scFv) binding data. 
         FIG. 8 . Bispecific antibodies neutralization assay results. 
         FIG. 9A-9B . Virus neutralization. (A) Dose-dependent neutralization of VSV-GPEBOV and VSV-GPSUDV by scKZ52-F4 LCN, scKZ52-F4 HCC, scKZ52-E10 LCN, and scKZ52-E10 HCC. Calculated IC50 values are listed next to each curve. (B) Neutralization of authentic viruses by PRNT assay, with IC50 values listed. 
         FIG. 10A-10D . Animal challenge experiments. Percent survival and median percent weight change for mouse-adapted EBOV (A) and SUDV (B) challenges with antibody treatment. Mice were treated with a single post-exposure dose (200 μg at 24 hours) for EBOV or two post-exposure doses (500 μg at days +1 and +4) for SUDV. Statistical p-values are listed against PBS and F4 controls for EBOV and against Z.6D8 control for SUDV (****, p&lt;0.0001; **, p&lt;0.01; *, p&lt;0.05; p-values greater that 0.05 are listed numerically; na, not applicable). (C and D) Rechallenge of surviving mice from initial challenge cohorts, with no further antibody treatment. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Herein is described A composition is provided comprising (1) a first single chain variable fragment (scFv) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a first species of filovirus, which first scFv is covalently joined to (2) a first polypeptide of an immunoglobulin G (IgG) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a second species of filovirus, wherein the first species of filovirus and second species of filovirus are different species. 
     In an embodiment of the composition, the first scFv comprises three different heavy chain CDRs and three different light chain CDRs, each CDR directed to the membrane glycoprotein pre-fusion core of the first species of filovirus. 
     In an embodiment of the composition, the IgG comprises at least three different heavy chain CDRs and at least three different light chain CDRs, each CDR directed to the membrane glycoprotein pre-fusion core of the second species of filovirus. 
     In an embodiment of the compositions, the first scFv is covalently joined at its N terminal to a C terminal of a first polypeptide of the IgG. In an embodiment of the compositions, the first polypeptide of the IgG is a heavy chain. In an embodiment of the compositions, the first polypeptide of the IgG is a light chain. 
     In an embodiment of the compositions, the first scFv is covalently joined at its C terminal to an N terminal of a first polypeptide of the IgG. In an embodiment of the compositions, the first polypeptide of the IgG is a heavy chain. In an embodiment of the compositions, the first polypeptide of the IgG is alight chain. 
     In an embodiment of the compositions, the scFv is covalently joined to the first polypeptide via a polypeptide linker. 
     In an embodiment of the compositions, the polypeptide linker comprises the sequence GGSAGSAGSAGSGGS (SEQ ID NO:17). 
     In an embodiment of the compositions, a V H  sequence of the first scFv has a sequence identical to V H  sequence of a human or a humanized antibody directed to the membrane glycoprotein pre-fusion core of the first species of filovirus. 
     In an embodiment of the compositions, a V L  sequence of the first scFv has a sequence identical to V L  sequence of a human or a humanized antibody directed to the membrane glycoprotein pre-fusion core of the first species of filovirus. 
     In an embodiment of the compositions, the V H  sequence of the scFv is joined to the V L  sequence of the first scFv by a polypeptide linker, in an embodiment of the compositions, the polypeptide linker is majority glycine residues. In an embodiment of the compositions, the polypeptide linker is GGGGSGGGGSGGGGS (SEQ ID NO:18). 
     In an embodiment of the compositions, the composition comprises a second scFv, wherein the second scFv is covalently joined to a second polypeptide of the IgG. In an embodiment of such compositions, a V L  sequence of the first scFv has a sequence identical to V L  sequence of a human or a humanized antibody directed to the membrane glycoprotein pre-fusion core of the first species of filovirus. In an embodiment of the compositions, a V H  sequence of the IgG has a sequence identical to V H  sequence of a human or a humanized IgG antibody directed to the membrane glycoprotein pre-fusion core of the second species of filovirus. In an embodiment of the compositions, a V L  sequence of the IgG has a sequence identical to V L  sequence of a human or a humanized IgG antibody directed to the membrane glycoprotein pre-fusion core of the second species of filovirus. 
     In an embodiment of the compositions, the IgG is a neutralizing antibody for the second species of filovirus. 
     In an embodiment of the compositions, the first species of filovirus and the second species of filovirus are both Ebolavirus species. In an embodiment of the compositions, the Ebola virus species are Zaire ebolavirus and Sudan ebolavirus. 
     A composition is also provided comprising (i) a first single chain variable fragment (scFv) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a first species of filovirus, which first scFv is covalently joined to (ii) a first polypeptide of an immunoglobulin G (IgG) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a second species of filovirus, the IgG having covalently joined thereto, at a different location from the attachment of (i) thereto. (iii) a second single chain variable fragment (scFv) comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a third species of filovirus, wherein the first species of filovirus and second species of filovirus and third species of filovirus are all different species. 
     In an embodiment of the composition, the first scFv comprises three different heavy chain CDRs and three different light chain CDRs, each CDR directed to the membrane glycoprotein pre-fusion core of the first species of filovirus, and the second scFv comprises three different heavy chain CDRs and three different light chain CDRs, each CDR directed to the membrane glycoprotein pre-fusion core of the third species of filovirus. In an embodiment of the composition, the IgG comprises at least three different heavy chain CDRs and at least three different light chain CDRs, each CDR directed to the membrane glycoprotein pre-fusion core of the second species of filovirus. 
     In an embodiment of the compositions, the first scFv is covalently joined at its N terminal to a C terminal of a first polypeptide of the IgG, and the second scFv is covalently joined to a different location on the IgG. In an embodiment of the compositions, the first polypeptide of the IgG is a heavy chain. In an embodiment of the compositions, the first polypeptide of the IgG is a light chain. 
     In an embodiment of the compositions, the first scFv is covalently joined at its C terminal to an N terminal of a first polypeptide of the IgG, and the second scFv is covalently joined to a different location on the IgG. In an embodiment of the compositions, the first polypeptide of the IgG is a heavy chain. In an embodiment of the compositions, the first poly peptide of the IgG is a light chain. 
     In an embodiment of the compositions, the first and second scFvs are each covalently joined to the first polypeptide, each via a separate polypeptide linker. In an embodiment of the compositions, the first and second scFvs are each covalently joined to different polypeptides of the IgG, each via a separate polypeptide linker. In an embodiment of the compositions, the polypeptide linkers each comprise the sequence GGSAGSAGSAGSGGS (SEQ ID NO:17). 
     In an embodiment of the compositions, a V H  sequence of the first scFv has a sequence identical to V H  sequence of a human or a humanized antibody directed to the membrane glycoprotein pre-fusion core of the first species of filovirus. In an embodiment of the compositions, a V H  sequence of the second scFv has a sequence identical to V H  sequence of a human or a humanized antibody directed to the membrane glycoprotein pre-fusion core of the third species of filovirus. 
     In an embodiment of the compositions, a V L  sequence of the first scFv has a sequence identical to V L  sequence of a human or a humanized antibody directed to the membrane glycoprotein pre-fusion core of the first species of filovirus. In an embodiment of the compositions, a V L  sequence of the second scFv has a sequence identical to V L  sequence of a human or a humanized antibody directed to the membrane glycoprotein pre-fusion core of the third species of filovirus. 
     In an embodiment of the compositions, the VH sequence of the first scFv is joined to the VL sequence of the scFv by a polypeptide linker. In an embodiment of the compositions, the VH sequence of the second scFv is joined to the VL sequence of the scFv by a polypeptide linker. In an embodiment of the compositions, the polypeptide linker is majority glycine residues. In an embodiment of the compositions, the polypeptide linker is GGGGSGGGGSGGGGS (SEQ ID NO:18). 
     In an embodiment of the compositions, the IgG is a neutralizing antibody for the second species of filovirus. 
     In an embodiment of the compositions, the first species of filovirus and the second species of filovirus and third species of filovirus are all Ebolavirus species. In an embodiment of the compositions, the Ebola virus species include Zaire ebolavirus and Sudan ebolavirus. In an embodiment of the compositions, the at least one species of filovirus and is an Ebolavirus species and at least one species of filovirus is a Marburg virus. 
     Also provided is an isolated nucleic acid encoding any of the compositions described herein. 
     Also provided is a method of treating a filovirus infection in a subject comprising administering an amount of a bispecific composition described herein to the subject effective to treat a filovirus infection in a subject. 
     Also provided is a method of preventing a filovirus infection in a subject comprising administering an amount of a bispecific composition described herein to the subject effective to inhibit a filovirus infection in a subject. 
     Also provided is a method of preventing a filovirus infection of a mammalian cell comprising contacting the filovirus with an amount of a bispecific composition described herein effective to inhibit a filovirus infection of a mammalian cell. In an embodiment of the method, the cell is an antigen presenting cell. In an embodiment of the method, the cell is a dendritic cell or a macrophage. In an embodiment of the method, the cell is human. 
     Also provided is a method of treating a filovirus infection in a subject comprising administering an amount of a trispecific composition described herein to the subject effective to treat a filovirus infection in a subject. 
     Also provided is a method of preventing a filovirus infection in a subject comprising administering an amount of a trispecific composition described herein to the subject effective to inhibit a filovirus infection in a subject. 
     Also provided is a method of preventing a filovirus infection of a mammalian cell comprising contacting the filovirus with an amount of a trispecific composition described herein effective to inhibit a filovirus infection of a mammalian cell. In an embodiment of the method, the cell is an antigen presenting cell. In an embodiment of the method, the cell is a dendritic cell or a macrophage. In an embodiment of the method, the cell is human. 
     Also provided is a method of treating a filovirus infection in a subject comprising administering an amount of a bispecific composition described herein to the subject effective to treat a filovirus infection in a subject. Also provided is a method of preventing a filovirus infection in a subject comprising administering an amount of a bispecific composition described herein to the subject effective to inhibit a filovirus infection in a subject. Also provided is a method of preventing a filovirus infection of a mammalian cell comprising contacting the filovirus with an amount of a bispecific composition described herein effective to inhibit a filovirus infection of a mammalian cell. In an embodiment of the method, the cell is an antigen presenting cell. In an embodiment of the method, the cell is a dendritic cell or a macrophage. In an embodiment of the method, the cell is human. Also provided is a method of treating a filovirus infection in a subject comprising administering an amount of a trispecific composition described herein to the subject effective to treat a filovirus infection in a subject. Also provided is a method of preventing a filovirus infection in a subject comprising administering an amount of a trispecific composition described herein to the subject effective to inhibit a filovirus infection in a subject. Also provided is a method of preventing a filovirus infection of a mammalian cell comprising contacting the filovirus with an amount of a trispecific composition described herein effective to inhibit a filovirus infection of a mammalian cell. In an embodiment of the method, the cell is an antigen presenting cell. In an embodiment of the method, the cell is a dendritic cell or a macrophage. In an embodiment of the method, the cell is human. In an embodiment of all of the methods described herein, the subject is human. 
     Also provided is a portion of an recombinant dual-variable-domain antibody, the portion comprising: 
     (1) a heavy chain amino acid sequence comprising in N terminal to C terminal order (i) a first V H  amino acid sequence comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a first species of filovirus, (ii) a 4, 5, 6, 7, or 8 amino acid first linker sequence. (iii) a second V H  amino acid sequence comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a second species of filovirus, (iv) an immunoglobulin G C H 1 amino acid sequence, (v) an immunoglobulin G hinge amino acid sequence. (vi) an immunoglobulin G C H 2 amino acid sequence, (vii) an immunoglobulin G C H 3 amino acid sequence, which is bound via one or more inter-chain disulfide bond(s) to (2) a light chain amino acid sequence comprising in N terminal to C terminal order (i) a first V L  amino acid sequence comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a first species of filovirus, (ii) a 4, 5, 6, 7, or 8 amino acid second linker sequence, (iii) a second V 1  amino acid sequence comprising at least one CDR directed to a membrane glycoprotein pre-fusion core of a second species of filovirus, (iv) an immunoglobulin G C L  amino acid sequence, wherein the first species of filovirus and second species of filovirus are different species. 
     In an embodiment. (1) and (2) are bound via an inter-chain disulfide bond between the C H 1 amino acid sequence and the C L  amino acid sequence. Also provided is a construct comprising two of the recombinant dual-variable-domain antibodies (or portions) as described together by one or more disulfide bonds between the heavy chain amino acid sequence of each. In an embodiment, the two recombinant dual-variable-domain antibodies are joined together by two disulfide bonds between the immunoglobulin G hinge amino acid sequences of each. In an embodiment, the 4, 5, 6, 7, or 8 amino acid first linker sequence is a 6 amino acid first linker sequence. In an embodiment, the 6 amino acid first linker sequence is ASTKGP (SEQ ID NO:41). In an embodiment the 4, 5, 6, 7, or 8 amino acid second linker sequence is 5 amino acid second linker sequence. In an embodiment, the 5 amino acid second linker sequence is TVAAP (SEQ ID NO:42). 
     In an embodiment, the first V H  amino acid sequence comprises three different heavy chain CDRs each of the three CDRs directed to the membrane glycoprotein pre-fusion core of the first species of filovirus. In an embodiment, the first V L  amino acid sequence comprises three different light chain CDRs each of the three CDRs directed to the membrane glycoprotein pre-fusion core of the first species of filovirus. In an embodiment, the second V H  amino acid sequence comprises three different heavy chain CDRs each of the three CDRs directed to the membrane glycoprotein pre-fusion core of the second species of filovirus. In an embodiment, the second V L  amino acid sequence comprises three different light chain CDRs each of the three CDRs directed to the membrane glycoprotein pre-fusion core of the second species of filovirus. 
     In an embodiment, the first species of filovirus and the second species of filovirus are both Ebolavirus species. In an embodiment, the Ebola virus species are Zaire ebolavirus and Sudan ebolavirus. 
     Also provided is an isolated nucleic acid encoding a recombinant dual-variable-domain antibody or a construct as described herein. In an embodiment, the isolated nucleic acid is, or comprises, a cDNA. 
     Also provided is a method of treating a filovirus infection in a subject comprising administering an amount of the recombinant dual-variable-domain antibody or construct described herein to the subject effective to treat a filovirus infection in a subject. Also provided is a method of preventing a filovirus infection in a subject comprising administering an amount of the recombinant dual-variable-domain antibody or construct described herein to the subject effective to inhibit a filovirus infection in a subject. Also provided is a method of preventing a filovirus infection of a mammalian cell comprising contacting the filovirus with an amount of the recombinant dual-variable-domain antibody or construct described herein effective to inhibit a filovirus infection of a mammalian cell. In an embodiment, the cell is an antigen presenting cell. In an embodiment, the cell is a dendritic cell or a macrophage. In an embodiment, the cell is human. 
     In an embodiment of all of the methods described herein, the subject is human. 
     As used herein, “treating” a specified condition means ameliorating one or more symptoms of an extant condition, for example, a filovirus infection. 
     As used herein, “preventing” a specified condition means reducing the development of, or reducing the extent of, one or more symptoms of the condition, for example a filovirus infection, as compared to the development or extent the condition takes in the absence of preventative treatment. In an embodiment, “preventing” as used herein does not mean an absolute prevention, but a lessened extent of the condition brought about prophylactically. 
     Exemplary E10/F4-KZ52 scFv Bispecifics Sequences: the following exemplary amino acid sequences are provided, for the compositions of the invention as relating to the embodiments of antibodies E10 and F4, with non-limiting exemplary nucleotide sequences (in view of the degeneracy of the genetic code). 
     E10-KZ52 HC N′ Fusion Sequence: 
     
       
         
           
               
            
               
                 Amino Acid (SEQ ID NO: 1): 
               
               
                 EVQLLESGGLVKPGGSLRLSACCSGFTLINYRMNWVRQAPGKGLEWVSSI 
               
               
                   
               
               
                 SSSSSYIHYADSVKGRFTISRDNAENSLYLQMNSLRAEDTAVYYCVREGP 
               
               
                   
               
               
                 RATGYSMADVFDIWGQGTMVTVSS GGGGSGGGGSGGGGS ELVMTQSPDSL 
               
               
                   
               
               
                 AVSLGERATINCKSSQSVLYSSNNKSYLAWYQQKPGQPPKLLIYWASTRE 
               
               
                   
               
               
                 SGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSAPLTFGGGTKVE 
               
               
                   
               
               
                 IK GGSAGSAGSAGSGGS EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYD 
               
               
                   
               
               
                 IHWVRQAPGKGLEWVAYINPGGGNTYYADSVKGRFTISADTSKNTAYLQM 
               
               
                   
               
               
                 NALRAEDTAVYYCARQLYGNSFMDYWGQGTLVTVSS ASTKGPSVFPLAPS   
               
               
                   
               
               
                 
                   SKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS 
                 
               
               
                   
               
               
                 
                   LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCDKTHT 
                 
               
               
                   
               
               
                 
                   CPPCPAPELLGRPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF 
                 
               
               
                   
               
               
                 
                   NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 
                 
               
               
                   
               
               
                 
                   KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS 
                 
               
               
                   
               
               
                 
                   DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC 
                 
               
               
                   
               
               
                 
                   SVMHEALHNHYTQKSLSLSPGK 
                 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. Italicized region is CH1-CH3 for the HC and the CL region. 
     
       
         
           
               
            
               
                 Nucleotide (SEQ ID NO: 2): 
               
               
                 GAAGTGCAGTTACTGGAAAGCGGCGGCGGCCTGGTTAAACCTGGCGGTAG 
               
               
                   
               
               
                 TCTGCGTCTGAGTTGCGCCGCCAGCGGTTTCACCCTGATCAACTACCGCA 
               
               
                   
               
               
                 TGAACTGGGTGCGTCAGGCACCGGGTAAAGGCCTGGAGTGGGTGAGCAGC 
               
               
                   
               
               
                 ATTAGCAGCAGCAGCAGCTATATTCACTACGCCGACAGCGTGAAAGGCCG 
               
               
                   
               
               
                 CTTTACCATCAGCCGCGACAATGCCGAGAACAGTCTGTATCTGCAGATGA 
               
               
                   
               
               
                 ACAGCCTAAGGGCGGAAGATACAGCCGTGTACTACTGTGTGCGCGAAGGC 
               
               
                   
               
               
                 CCTCGCGCAACCGGCTATAGCATGGCAGACGTGTTTGATATCTGGGGTCA 
               
               
                   
               
               
                 GGGCACCATGGTTACAGTTAGCAGTGGTGGTGGTGGTAGTGGTGGCGGTG 
               
               
                   
               
               
                 GTAGCGGTGGTGGTGGCAGTGAACTGGTGATGACCCAGAGCCCGGATAGC 
               
               
                   
               
               
                 TTAGCCGTGAGTCTGGGCGAAAGGGCGACCATTAACTGCAAAAGCAGCCA 
               
               
                   
               
               
                 GAGCGTGCTGTACAGCAGCAACAACAAGAGCTACCTGGCATGGTATCAGC 
               
               
                   
               
               
                 AAAAACCGGGTCAGCCTCCGAAACTGCTGATCTATTGGGCAAGCACCCGC 
               
               
                   
               
               
                 GAAAGTGGTGTTCCGGATCGCTTCAGCGGTAGTGGCAGCGGTACCGATTT 
               
               
                   
               
               
                 CACCCTGACCATCAGCAGTCTGCAGGCCGAGGACGTTGCAGTGTATTACT 
               
               
                   
               
               
                 GTCAGCAGTACTACAGCGCCCCGCTGACCTTTGGCGGCGGCACCAAAGTT 
               
               
                   
               
               
                 GAAATTAAGGGCGGCAGTGCAGGCAGCGCCGGTAGTGCCGGTAGTGGTGG 
               
               
                   
               
               
                 TAGCGAAGTTCAGCTGGTTGAAAGTGGCGGCGGTCTGGTGCAGCCTGGTG 
               
               
                   
               
               
                 GTAGTCTGCGTCTGAGTTGTGCCGCCAGCGGCTTTGCCTTCAATTACTAT 
               
               
                   
               
               
                 GACATTCATTGGGTTCGCCAGGCCCCGGGTAAAGGTCTGGAATGGGTTGC 
               
               
                   
               
               
                 ATATATCAACCCGGGTGGCGGTAACACCTACTATGCCGACAGCGTTAAGG 
               
               
                   
               
               
                 GTCGCTTCACCATCAGCGCAGATACCAGCAAAAACACCGCCTACCTGCAG 
               
               
                   
               
               
                 ATGAATAGCCTGCGTGCAGAAGATACCGCCGTTTACTACTGTGCCCGCCA 
               
               
                   
               
               
                 GCTGTACGGCAATAGCTTCATGGACTATTGGGGCCAGGGCACCTTAGTTA 
               
               
                   
               
               
                 CCGTGAGCAGC 
               
               
                   
               
               
                 Combined (SEQ ID NO: 1 and 2): 
               
               
                 gaagtgcagttactggaaagcggcggcggcctggttaaacctggcggtag 
               
               
                  E  V  Q  L  L  E  S  G  G  G  L  V  K  P  G  G  S 
               
               
                   
               
               
                 tctgcgtctgagttgcgccgccagcggtttcaccctgatcaactaccgca 
               
               
                   L  R  L  S  C  A  A  S  G  F  T  L  I  N  Y  R 
               
               
                   
               
               
                 tgaactgggtgcgtcaggcaccgggtaaaggcctggagtgggtgagcagc 
               
               
                 M  N  W  V  R  Q  A  P  G  K  G  L  E  W  V  S  S 
               
               
                   
               
               
                 attagcagcagcagcagctatattcactacgccgacagcgtgaaaggccg 
               
               
                  I  S  S  S  S  S  Y  I  H  Y  A  D  S  V  K  G  R 
               
               
                   
               
               
                 ctttaccatcagccgcgacaatgccgagaacagtctgtatctgcagatga 
               
               
                   F  T  I  S  R  D  N  A  E  N  S  L  Y  L  Q  M 
               
               
                   
               
               
                 acagcctaagggcggaagatacagccgtgtactactgtgtgcgcgaaggc 
               
               
                 N  S  L  R  A  E  D  T  A  V  Y  Y  C  V  R  E  G 
               
               
                   
               
               
                 cctcgcgcaaccggctatagcatggcagacgtgtttgatatctggggtca 
               
               
                  P  R  A  T  G  Y  S  M  A  D  V  F  D  I  W  G  Q 
               
               
                   
               
               
                 gggcaccatggttacagttagcagtggtggtggtggtagtggtggcggtg 
               
               
                   G  T  M  V  T  V  S  S  G  G  G  G  S  G  G  G  
               
               
                   
               
               
                 gtagcggtggtggtggcagtgaactggtgatgacccagagcccggatagc 
               
               
                 G  S  G  G  G  G  S  E  L  V  M  T  Q  S  P  D  S 
               
               
                   
               
               
                 ttagccgtgagtctgggcgaaagggcgaccattaactgcaaaagcagcca 
               
               
                  L  A  V  S  L  G  E  R  A  T  I  N  C  K  S  S  Q 
               
               
                   
               
               
                 gagcgtgctgtacagcagcaacaacaagagctacctggcatggtatcagc 
               
               
                   S  V  L  Y  S  S  N  N  K  S  Y  L  A  W  Y  Q 
               
               
                   
               
               
                 aaaaaccgggtcagcctccgaaactgctgatctattgggcaagcacccgc 
               
               
                 Q  K  P  G  Q  P  P  K  L  L  I  Y  W  A  S  T  R 
               
               
                   
               
               
                 gaaagtggtgttccggatcgcttcagcggtagtggcagcggtaccgattt 
               
               
                  E  S  G  V  P  D  R  F  S  G  S  G  S  G  T  D  F 
               
               
                   
               
               
                 caccctgaccatcagcagtctgcaggccgaggacgttgcagtgtattact 
               
               
                   T  L  T  I  S  S  L  Q  A  E  D  V  A  V  Y  Y   
               
               
                   
               
               
                 gtcagcagtactacagcgccccgctgacctttggcggcggcaccaaagtt 
               
               
                 C  Q  Q  Y  Y  S  A  P  L  T  F  G  G  G  T  K  V 
               
               
                   
               
               
                 gaaattaagggcggcagtgcaggcagcgccggtagtgccggtagtggtgg 
               
               
                  E  I  K  G  G  S  A  G  S  A  G  S  A  G  S  G  G 
               
               
                   
               
               
                 tagcgaagttcagctggttgaaagtggcggcggtctggtgcagcctggtg 
               
               
                   S  E  V  Q  L  V  E  S  G  G  G  L  V  Q  P  G 
               
               
                   
               
               
                 gtagtctgcgtctgagttgtgccgccagcggctttgccttcaattactat 
               
               
                 G  S  L  R  L  S  C  A  A  S  G  F  A  F  N  Y  Y 
               
               
                   
               
               
                 gacattcattgggttcgccaggccccgggtaaaggtctggaatgggttgc 
               
               
                  D  I  H  W  V  R  Q  A  P  G  K  G  L  E  W  V  A 
               
               
                   
               
               
                 atatatcaacccgggtggcggtaacacctactatgccgacagcgttaagg 
               
               
                   Y  I  N  P  G  G  G  N  T  Y  Y  A  D  S  V  K   
               
               
                   
               
               
                 gtcgcttcaccatcagcgcagataccagcaaaaacaccgcctacctgcag 
               
               
                 G  R  F  T  I  S  A  D  T  S  K  N  T  A  Y  L  Q 
               
               
                   
               
               
                 atgaatagcctgcgtgcagaagataccgccgtttactactgtgcccgcca 
               
               
                  M  N  S  L  R  A  E  D  T  A  V  Y  Y  C  A  R  Q 
               
               
                   
               
               
                 gctgtacggcaatagcttcatggactattggggccagggcaccttagtta 
               
               
                   L  Y  G  N  S  F  M  D  Y  W  G  Q  G  T  L  V   
               
               
                   
               
               
                 ccgtgagcagc 
               
               
                 T  V  S  S 
               
               
                   
               
               
                 E10-KZ52 LC N′ Fusion Sequence: 
               
               
                 Amino Acid (SEQ ID NO: 3): 
               
               
                 EVQLLESGGGLVKPGGSLRLSCAASGFTLINYRMNWVRQAPGKGLEWVSS 
               
               
                   
               
               
                 ISSSSSYIHYADSVKGRFTISRDNAENSLYLQMNSLRAEDTAVYYCVREG 
               
               
                   
               
               
                 PRATGYSMADVFDIWGQGTMVTVSS GGGGSGGGGSGGGGS ELVMTQSPDS 
               
               
                   
               
               
                 LAVSLGERATINCKSSQSVLYSSNNKSYLAWYQQKPGQPPKLLIYWASTR 
               
               
                   
               
               
                 ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSAPLTFGGGTKV 
               
               
                   
               
               
                 EIK GGSAGSAGSAGSGGS DIQMTQSPSSLSASVGDRVTITCRASQDVTTA 
               
               
                   
               
               
                 VAWYQQKPGKAPKLLIYWASRLHNGVPSRFSGSGSGTDFTLTISSLQPED 
               
               
                   
               
               
                 FATYYCQQHYSTPLTFGQGTKVEIK RTVAAPSVFIFPPSDEQLKSGTASV   
               
               
                   
               
               
                 
                   VCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK 
                 
               
               
                   
               
               
                 
                   ADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSDYKDDDDK 
                 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker poly peptide. Italicized region is CH1-CH3 for the HC and the CL region. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 4): 
                   
               
               
                 GAAGTGCAGCTGCTGGAAAGCGGTGGCCGTCTGGTTAAACCTGGCGGTAGTCT 
               
               
                   
               
               
                 GCGCCTGAGTTGCGCCGCCAGCGGTTTTACACTGATCAACTATCGCATGAACTG 
               
               
                   
               
               
                 GGTGCGTCAGGCACCGGGTAAGGGTCTGGAGTGGGTTAGCAGCATTAGTAGCA 
               
               
                   
               
               
                 GCAGCAGTTACATTCACTACGCCGATAGCGTGAAAGGCCGCTTCACAATTAGCC 
               
               
                   
               
               
                 GCGATAACGCCGAGAACAGCCTGTATCTGCAGATGAACAGTTTACGCGCCGAA 
               
               
                   
               
               
                 GATACCGCCGTGTATTATTGCGTTCGCGAAGGTCCGCGTGCAACCGGCTACAGC 
               
               
                   
               
               
                 ATGGCCGACGTTTTCGATATTTGGGGTCAGGGCACCATGGTGACAGTTAGTAGC 
               
               
                   
               
               
                 GGTGGTGGTGGTAGTGGTGGTGGCGGCAGCGGTGGTGGTGGTAGTGAACTGGT 
               
               
                   
               
               
                 GATGACCCAGAGCCCGGATAGCCTGGCAGTGAGCCTGGGTGAGCGTGCCACCA 
               
               
                   
               
               
                 TCAATTGCAAAAGCAGCCAGAGCGTGCTGTACAGCAGCAACAACAAGAGTTAC 
               
               
                   
               
               
                 CTGGCCTGGTACCAACAGAAACCGGGCCAGCCGCCGAAACTGCTGATTTATTGG 
               
               
                   
               
               
                 GCCAGTACCCGCGAAAGCGGCGTGCCTGATCGTTTTAGTGGCAGCGGTAGCGG 
               
               
                   
               
               
                 CACCGACTTTACCCTGACCATTAGCAGCCTGCAGGCCGAGGATGTGGCAGTGTA 
               
               
                   
               
               
                 TTACTGCCAGCAGTATTACAGCGCCCCGTTAACCTTTGGCGGCGGTACCAAAGT 
               
               
                   
               
               
                 GGAGATCAAAGGTGGCAGTGCAGGCAGCGCCGGTAGTGCAGGTAGTGGTGGTA 
               
               
                   
               
               
                 GCGACATCCAGATGACACAGAGTCCGAGCAGCCTGAGTGCCAGCGTTGGTGAC 
               
               
                   
               
               
                 CGTGTGACCATTACCTGCCGTGCCAGCCAGGATGTTACCACAGCCGTTGCATGG 
               
               
                   
               
               
                 TATCAGCAGAAGCCGGGTAAGGCCCCTAAGTTACTGATCTACTGGGCAAGCCG 
               
               
                   
               
               
                 CCTGCATAACGGTGTGCCGAGCCGCTTTAGCGGCAGTGGTAGCGGTACCGATTT 
               
               
                   
               
               
                 GACCCTGACCATCAGCAGTCTGCAGCCGGAAGATTTCGCAACCTACTACTGTCA 
               
               
                   
               
               
                 GCCAGCATTACAGCACCCCGCTGACCTTTGGCCAGGGCACCAAAGTGGAAATTA 
               
               
                   
               
               
                 AA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 3 and 4): 
               
               
                 gaagtgcagctgctggaaagcggtggcggtctggttaaacctggcggtagtctgcgcctg 
               
               
                  E  V  Q  L  V  E  S  G  G  G  L  V  Q  P  G  G  S  L  R  L 
               
               
                   
               
               
                 agttgcgccgccagcggttttacactgatcaactatcgcatgaactgggtgcgtcaggca 
               
               
                  S  C  A  A  S  G  F  T  L  I  N  Y  R  M  N  W  V  R  Q  A 
               
               
                   
               
               
                 ccgggtaagggtctggagtgggttagcagcattagtagcagcagcagttacattcactac 
               
               
                  P  G  K  G  L  E  W  V  S  S  I  S  S  S  S  S  Y  I  H  Y 
               
               
                   
               
               
                 gccgatagcgtgaaaggccgcttcacaattagccgcgataacgccgagaacagcctgtat 
               
               
                  A  D  S  V  K  G  R  F  T  I  S  R  D  N  A  E  N  S  L  Y 
               
               
                   
               
               
                 ctgcagatgaacagtttacgcgccgaagataccgccgtgtattattgcgttcgcgaaggt 
               
               
                  L  Q  M  N  S  L  R  A  E  D  T  A  V  Y  Y  C  V  R  E  G 
               
               
                   
               
               
                 ccgcgtgcaaccggctacagcatggccgacgttttcgatatttggggtcagggcaccatg 
               
               
                  P  R  A  T  G  Y  S  M  A  D  V  F  D  I  W  G  Q  G  T  M 
               
               
                   
               
               
                 gtgacagttagtagcggtggtggtggtagtggtggtggcggcagcggtggtggtggtagt 
               
               
                  V  T  V  S  S  G  G  G  G  S  G  G  G  G  S  G  G  G  G  S 
               
               
                   
               
               
                 gaactggtgatgacccagagcccggatagcctggcagtgagcctgggtgagcgtgccacc 
               
               
                  E  L  V  M  T  Q  S  P  D  S  L  A  V  S  L  G  E  R  A  T 
               
               
                   
               
               
                 atcaattgcaaaagcagccagagcgtgctgtacagcagcaacaacaagagttacctggcc 
               
               
                  I  N  C  K  S  S  Q  S  V  L  Y  S  S  N  N  K  S  Y  L  A 
               
               
                   
               
               
                 tggtaccaacagaaaccgggccagccgccgaaactgctgatttattgggccagtacccgc 
               
               
                  W  Y  Q  Q  K  P  G  Q  P  P  K  L  L  I  Y  W  A  S  T  R 
               
               
                   
               
               
                 gaaagcggcgtgcctgatcgttttagtggcagcggtagcggcaccgactttaccctgacc 
               
               
                  E  S  G  V  P  D  R  F  S  G  S  G  S  G  T  D  F  T  L  T  
               
               
                   
               
               
                 attagcagcctgcaggccgaggatgtggcagtgtattactgccagcagtattacagcgcc 
               
               
                  I  S  S  L  Q  A  E  D  V  A  V  Y  Y  C  Q  Q  Y  Y  S  A 
               
               
                   
               
               
                 ccgttaacctttggcggcggtaccaaagtggagatcaaaggtggcagtgcaggcagcgcc 
               
               
                  P  L  T  F  G  G  G  T  K  V  E  I  K  G  G  S  A  G  S  A 
               
               
                   
               
               
                 ggtagtgcaggtagtggtggtagcgacatccagatgacacagagtccgagcagcctgagt 
               
               
                  G  S  A  G  S  G  G  S  D  I  Q  M  T  Q  S  P  S  S  L  S 
               
               
                   
               
               
                 gccagcgttggtgaccgtgtgaccattacctgccgtgccagccaggatgttaccacagcc 
               
               
                  A  S  V  G  D  R  V  T  I  T  C  R  A  S  Q  D  V  T  T  A 
               
               
                   
               
               
                 gttgcatggtatcagcagaagccgggtaaggcccctaagttactgatctactgggcaagc 
               
               
                  V  A  W  Y  Q  Q  K  P  G  K  A  P  K  L  L  I  Y  W  A  S 
               
               
                   
               
               
                 cgcctgcataacggtgtgccgagccgctttagcggcagtggtagcggtaccgatttcacc 
               
               
                  R  L  H  N  G  V  P  S  R  F  S  G  S  G  S  G  T  D  F  T 
               
               
                   
               
               
                 ctgaccatcagcagtctgcagccggaagatttcgcaacctactactgtcagcagcattac 
               
               
                  L  T  I  S  S  L  Q  P  E  D  F  A  T  Y  Y  C  Q  Q  H  Y 
               
               
                   
               
               
                 agcacccCgctgacctttggccagggcaccaaagtggaaattaaa 
               
               
                  S  T  P  L  T  F  G  Q  G  T  K  V  E  I  K 
               
               
                   
               
               
                 E10-KZ52 HC C′ Fusion Sequence: 
               
               
                 Amino Acid (SEQ ID NO: 5): 
               
               
                 EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDIHWVRQAPGKGLEVWV 
               
               
                   
               
               
                 AYINPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQLYGN 
               
               
                   
               
               
                 SFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEFVTVS 
               
               
                   
               
               
                 WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDK 
               
               
                   
               
               
                 KVEPKSCDKTHTCDKTHTCPPCPAPELLGRPSVFLFPPKPKD T LMISRTPEVTCVVV 
               
               
                   
               
               
                 DVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE 
               
               
                   
               
               
                 YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS 
               
               
                   
               
               
                 DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE 
               
               
                   
               
               
                 ALHNHY T QKSLSLSPGK GGSAGSAGSAGSGGS EVQLLESGGGLVKPGGSLRLSCA 
               
               
                   
               
               
                 ASGFTLINYRMNWVRQAPGKGLEWVSSISSSSSYIHYADSVKGRFTISRDNAENSLY 
               
               
                   
               
               
                 LQMNSLRAEDTAVYYCVREGPRATGYSMADVFDIWGQGTMVTVSS GGGGSGGG   
               
               
                   
               
               
                   GSGGGGS ELVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKSYLAWYQQKPGQP 
               
               
                   
               
               
                 PKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAYYYCQQYYSAPLTFGG 
               
               
                   
               
               
                 GTKVEIK 
               
            
           
         
       
     
     Underlined region is linker polypeptide. Bold region is fusion linker polypeptide. 
     Nucleotide (SEQ ID NO:6): 
     
       
         
           
               
               
            
               
                 GAGGTTCAGCTGGTGGAGTCTGGCGGTGGCCTGGTGCAGCCAGGGGGCTCACT 
                   
               
               
                   
               
               
                 CCGTTTGTCCTGTGCAGCTTCTGGCTTCGCGTTTAACTATTATGATATTCATTGG 
               
               
                   
               
               
                 GTGCGTCAGGCCCCGGGTAAGGGCCTGGAATGGGTTGCATATATTAACCCGGG 
               
               
                   
               
               
                 CGGTGGCAACACCTATTATGCTGATAGGGTCAAGGGCCGTTTCACTATAAGCGC 
               
               
                   
               
               
                 AGACACATCCAAAAACACAGCCTACCTACAAATGAACAGCTTAAGAGCTGAGG 
               
               
                   
               
               
                 ACACTGCCGTCTATTATTGTGCTCGCCAGCTGTATGGCAACAGCTTTATGGACT 
               
               
                   
               
               
                 ACTGGGGTCAAGGAACCCTGGTCACCGTCTCCTCGGCTAGGACCAAGGGTCCGA 
               
               
                   
               
               
                 GCGTGTTTCCTCTGGCACCTAGCAGTAAAAGCACCAGTGGTGGTACAGCAGCCC 
               
               
                   
               
               
                 TGGGTTGCCTGGTGAAGGATTACTTTCCGGAGCCGGTGACCGTTAGTTGGAATA 
               
               
                   
               
               
                 GCGGCGCCCTGACCAGTGGCGTTCATACATTTCCGGCCGTGCTGCAGAGTAGTG 
               
               
                   
               
               
                 GCCTGTACAGCCTGAGTAGCGTTGTTACCGTTCCGAGCAGCAGCCTGGGCACCC 
               
               
                   
               
               
                 AGACCTATATTTGCAATGTTAACCATAAACCGAGCAACACAAAAGTTGATAAA 
               
               
                   
               
               
                 AAAGTTGAACCGAAGAGCTGTGACAAAACCCATACATGTGACAAAACACACAC 
               
               
                   
               
               
                 CTGCCCGCCTTGTCCGGCACCTGAGCTGCTGGGTCGCCCGAGCGTTTTTCTGTTT 
               
               
                   
               
               
                 CCTCCGAAACCGAAAGAC ACC [ . . . ] ACC CAGAAGAGTCTGAGCCTGAGTCCTGGC 
               
               
                   
               
               
                 AAAGGTGGATCCGCCGGTAGCGGCAGGTAGTGCAGGTAGTGGCGGCAGCGAAGT 
               
               
                   
               
               
                 TCAGCTGTTAGAAAGTGGCGGTGGTCTGGTTAAGCCGGGCGGTAGTCTGCGCCT 
               
               
                   
               
               
                 GAGCTGTGCAGCAAGTGGTTTCACCCTGATCAATTATCGTATGAACTGGGTGCG 
               
               
                   
               
               
                 CCAAGCCCCGGGTAAAGGTCTGGAGTGGGTTAGTAGTATCAGCAGCAGCAGCA 
               
               
                   
               
               
                 GTTACATCCACTATGCCGATAGCGTTAAGGGCCGCTTTACAATCAGCCGCGATA 
               
               
                   
               
               
                 ATGCCGAGAATAGCTTATACCTGCAAATGAACAGTCTAAGGGCGGAAGATACC 
               
               
                   
               
               
                 GCCGTTTACTACTGCGTTCGTGAAGGCCCTCGCGCAACAGGCTATAGCATGGCA 
               
               
                   
               
               
                 GACGTGTTCGACATTTGGGGTCAGGGCACCATGGTGACCGTTAGTAGCGGCGGT 
               
               
                   
               
               
                 GGTGGTAGTGGTGGTGGCGGTAGTGGTGGCGGTGGCAGCGAACTGGTGATGAC 
               
               
                   
               
               
                 CCAGAGTCCGGATAGCCTGGCCGTGAGCTTAGGCGAGCGTGCAACCATTAATTG 
               
               
                   
               
               
                 TAAAAGCAGTCAGAGTGTTCTGTATAGTAGCAATAACAAGAGCTATCTGGCCTG 
               
               
                   
               
               
                 GTATCAGCAGAAGCCGGGCCAGCCGCCGAAACTGCTGATTTACTGGGCAAGCA 
               
               
                   
               
               
                 CCCGCGAAAGTGGCGTGCCTGATCGCTTTAGTGGTAGCGGCAGCGGCACCGATT 
               
               
                   
               
               
                 TTACCCTGACCATTAGCAGTCTGCAGGCCGAGGACGTTGCCGTTTATTACTGCC 
               
               
                   
               
               
                 AGCAGTACTATAGCGCACCGCTGACATTTGGCGGTGGCACCAAGGTGGAAATT 
               
               
                   
               
               
                 AAATAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 5 and 6): 
               
               
                 gaggttcagctggtggagtctggcggtggcctggtgcagccagggggctcactccgtttg 
               
               
                  E  V  Q  L  V  E  S  G  G  G  L  V  Q  P  G  G  S  L  R  L  
               
               
                   
               
               
                 tcctgtgcagcttctggcttcgcgtttaactattatgatattcattgggtgcgtcaggcc 
               
               
                  S  C  A  A  S  G  F  A  F  N  Y  Y  D  I  H  W  V  R  Q  A 
               
               
                   
               
               
                 ccgggtaagggcctggaatgggttgcatatattaacccgggcggtggcaacacctattat 
               
               
                  P  G  K  G  L  E  W  V  A  Y  I  N  P  G  G  G  N  T  Y  Y 
               
               
                   
               
               
                 gctgatagcgtcaagggccgtttcactataagcgcagacacatccaaaaacacagcctac 
               
               
                  A  D  S  V  K  G  R  F  T  I  S  A  D  T  S  K  N  T  A  Y 
               
               
                   
               
               
                 ctacaaatgaacagcttaagagctgaggacactgccgtctattattgtgctcgccagctg 
               
               
                  L  Q  M  N  S  L  R  A  E  D  T  A  V  Y  Y  C  A  R  Q  L 
               
               
                   
               
               
                 tatggcaacagctttatggactactggggtcaaggaaccctggtcaccgtctcctcggct 
               
               
                  Y  G  N  S  F  M  D  Y  W  G  Q  G  T  L  V  T  V  S  S  A 
               
               
                   
               
               
                 agcaccaagggtccgagcgtgtttcctctggcacctagcagtaaaagcaccagtggtggt 
               
               
                  S  T  K  G  P  S  V  F  P  L  A  P  S  S  K  S  T  S  G  G 
               
               
                   
               
               
                 acagcagccctgggttgcctggtgaaggattactttccggagccggtgaccgttagttgg 
               
               
                  T  A  A  L  G  C  L  V  K  D  Y  F  P  E  P  V  T  V  S  W 
               
               
                   
               
               
                 aatagcggcgccctgaccagtggcgttcatacatttccggccgtgctgcagagtagtggc 
               
               
                  N  S  G  A  L  T  S  G  V  H  T  F  P  A  V  L  Q  S  S  G 
               
               
                   
               
               
                 ctgtacagcctgagtagcgttgttaccgttccgagcagcagcctgggcacccagacctat 
               
               
                  L  Y  S  L  S  S  V  V  T  V  P  S  S  S  L  G  T  Q  T  Y 
               
               
                   
               
               
                 atttgcaatgttaaccataaaccgagcaacacaaaagttgataaaaaagttgaaccgaag 
               
               
                  I  C  N  V  N  H  K  P  S  N  T  K  V  D  K  K  V  E  P  K 
               
               
                   
               
               
                 agctgtgacaaaacccatacatgtgacaaaacacacacctgcccgccttgtccggcacct 
               
               
                  S  C  D  K  T  H  T  C  D  K  T  H  T  C  P  P  C  P  A  P 
               
               
                   
               
               
                 gagctgctgggtcgcccgagcgtttttctgtttcctccgaaaccgaaagacacc [ . . . ] 
               
               
                  E  L  L  G  R  P  S  V  F  L  F  P  P  K  P  K  D  T  [ . . . ] 
               
               
                   
               
               
                 acccagaagagtctgagcctgagtcctggcaaaggtggatccgccggtagcgcaggtagt 
               
               
                  T  Q  K  S  L  S  L  S  P  G  K  G  G  S  A  G  S  A  G  S 
               
               
                   
               
               
                 gcaggtagtggcggcagcgaagttcagctgttagaaagtggcggtggtctggttaagcgg 
               
               
                  A  G  S  G  G  S  E  V  Q  L  L  E  S  G  G  G  L  V  K  P 
               
               
                   
               
               
                 ggcggtagtctgcgcctgagctgtgcagcaagtggtttcaccctgatcaattatcgtatg 
               
               
                  G  G  S  L  R  L  S  C  A  A  S  G  F  T  L  I  N  Y  R  M 
               
               
                   
               
               
                 aactgggtgcgccaagccccgggtaaaggtctggagtgggttagtagtatcagcagcagc 
               
               
                  N  W  V  R  Q  A  P  G  K  G  L  E  W  V  S  S  I  S  S  S 
               
               
                   
               
               
                 agcagttacatccactatgccgatagcgttaagggccgctttacaatcagccgcgataat 
               
               
                  S  S  Y  I  H  Y  A  D  S  V  K  G  R  F  T  I  S  R  D  N 
               
               
                   
               
               
                 gccgagaatagcttatacctgcaaatgaacagtctaagggcggaagataccgccgtttac 
               
               
                  A  E  N  S  L  Y  L  Q  M  N  S  L  R  A  E  D  T  A  V  Y 
               
               
                   
               
               
                 tactgcgttcgtgaaggccctcgcgcaacaggctatagcatggcagacgtgttcgacatt 
               
               
                  Y  C  V  R  E  G  P  R  A  T  G  Y  S  M  A  D  V  F  D  I 
               
               
                   
               
               
                 tggggtcagggcaccatggtgaccgttagtagcggcggtggtggtagtggtggtggcggt 
               
               
                  W  G  Q  G  T  M  V  T  V  S  S  G  G  G  G  S  G  G  G  G 
               
               
                   
               
               
                 agtggtggcggtggcaccgaactggtgatgacccagagtccggatagcctggccgtgagc 
               
               
                  S  G  G  G  G  S  E  L  V  M  T  Q  S  P  D  S  L  A  V  S 
               
               
                   
               
               
                 ttaggcgagcgtgcaaccattaattgtaaaagcagtcagagtgttctgtatagtagcaat 
               
               
                  L  G  E  R  A  T  I  N  C  K  S  S  Q  S  V  L  Y  S  S  N 
               
               
                   
               
               
                 aacaagagctatctggcctggtatcagcagaagccgggccagccgccgaaactgctgatt 
               
               
                  N  K  S  Y  L  A  W  Y  Q  Q  K  P  G  Q  P  P  K  L  L  I 
               
               
                   
               
               
                 tactgggcaagcacccgcgaaagtggcgtgcctgatcgctttagtggtagcggcagcggc 
               
               
                  Y  W  A  S  T  R  E  S  G  V  P  D  R  F  S  G  S  G  S  G 
               
               
                   
               
               
                 accgattttaccctgaccattagcagtctgacggccgaggacgttgccgtttattactgc 
               
               
                  T  D  F  T  L  T  I  S  S  L  Q  A  E  D  V  A  V  Y  Y  C 
               
               
                   
               
               
                 cagcagtactatagcgcaccgctgacatttggcggtggcaccaaggtggaaattaaataa 
               
               
                  Q  Q  Y  Y  S  A  P  L  T  F  G  G  G  T  K  V  E  I  K  - 
               
               
                   
               
               
                 E10-KZ52 LC C′ Fusion Sequence: 
               
               
                 Amino Acid (SEQ ID NO: 7): 
               
               
                 DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIY 
               
               
                   
               
               
                 WASRLHNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQGTKVEI 
               
               
                   
               
               
                 KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVGWKVDNALQSGNSQES 
               
               
                   
               
               
                 VTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGS G   
               
               
                   
               
               
                   GSAGSAGSAGSGGS EVQLLESGGGLVKPGGSLRLSCAASGFTLINYRMNWVRQAP 
               
               
                   
               
               
                 GKGLEWVSSISSSSSYIHYADSVKGRFTISRDNAENSLYLQMNSLRAEDTAVYYCY 
               
               
                   
               
               
                 REGFRATGYSMADVFDIWGQGTMVTVSS GGGGSGGGGSGGGGS ELVMTQSPDSL 
               
               
                   
               
               
                 AVSLGERATINCKSSQSVLYSSNNKSYLAWYQQKPGQPPKLLIYWASTRESGVPDR 
               
               
                   
               
               
                 FSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSAPLTFGGGTKVEIK 
               
            
           
         
       
     
     Underlined region is linker polypeptide. Bold region is fusion linker polypeptide. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 8): 
                   
               
               
                 GATATCCAGATGACCCAGTCCCCGAGCTCCCTGTCCGCCTCTGTGGGCGATAGG 
               
               
                   
               
               
                 GTCACCATCACCTGCCGGGCGAGCCAGGATGTGACCACCGCTGTAGCCTGGTAT 
               
               
                   
               
               
                 CAACAGAAACCAGGAAAAGCTCCGAAGCTTCTGATTTACTGGGCGAGCCGTCTT 
               
               
                   
               
               
                 CATAATGGCGTGCCGAGCCGCTTTAGCGGCAGCGGCTCCGGGACGGATTTCACT 
               
               
                   
               
               
                 CTGACCATCAGCAGTCTGCAGCCGGAAGACTTCGCAACTTATTACTGTCAGCAA 
               
               
                   
               
               
                 CATTATAGCACCCCGCTGACGTTCGGACAGGGTACCAAGGTGGAGATCAAACG 
               
               
                   
               
               
                 TACGGTGGCAGCACCGAGCGTGTTTATCTTTCCGCCGAGCGACGAACAACTGAA 
               
               
                   
               
               
                 AAGTGGCACAGCCAGCGTGGTGTGTTTACTGAACAACTTCTATCCTCGCGAGGC 
               
               
                   
               
               
                 CAAGGTGCAGTGGAAAGTGGACAATGCACTGCAGAGTGGCAATAGCCAGGAGA 
               
               
                   
               
               
                 GCGTGACCGAACAGGATAGCAAAGATAGCACCTATAGCCTGAGTAGCACCCTG 
               
               
                   
               
               
                 ACCCTGAGCAAGGCCGATTATGAGAAGCACAAGGTGTATGCATGCGAGGTTAC 
               
               
                   
               
               
                 CCATCAGGGCCTGAGCAGCCCGGTGACCAAAAGCTTTAACCGTGGCGAATGCG 
               
               
                   
               
               
                 GTGGTAGTGGTGGATCCGCCGGTAGCGCAGGTAGTGCAGGTAGTGGCGGCAGC 
               
               
                   
               
               
                 GAAGTTCAGCTGTTAGAAAGTGGCGGTGGTCTGGTTAAGCCGGGCGGTAGTCTG 
               
               
                   
               
               
                 CGCCTGAGCTGTGCAGCAAGTGGTTTCACCCTGATCAATTATCGTATGAACTGG 
               
               
                   
               
               
                 GTGCGCCAAGCCCCGGGTAAAGGTCTGGAGTGGGTTAGTAGTATCAGCAGCAG 
               
               
                   
               
               
                 CAGCAGTTACATCCACTATGCCGATAGCGTTAAGGGCCGCTTTACAATCAGCCG 
               
               
                   
               
               
                 CGATAATGCCGAGAATAGCTTATACCTGCAAATGAACAGTCTAAGGGCGGAAG 
               
               
                   
               
               
                 ATACCGCCGTTTACTACTGCGTTCGTGAAGGCCCTCGCGCAACAGGCTATAGCA 
               
               
                   
               
               
                 TGGCAGACGTGTTCGACATTTGGGGTCAGGGCACCATGGTGACCGTTAGTAGCG 
               
               
                   
               
               
                 GCGGTCGGTGGTAGTGGTGGTGGCGGTAGTGGTGGCGGTGGCAGCGAACTGGTG 
               
               
                   
               
               
                 ATGACCCAGAGTCCGGATAGCCTGGCCGTGAGCTTAGGCGAGCGTGCAACCAT 
               
               
                   
               
               
                 TAATTGTAAAAGCAGTCAGAGTGTTCTGTATAGTAGCAATAACAAGAGCTATCT 
               
               
                   
               
               
                 GGCCTGGTATCAGCAGAAGCCGGGCCAGCCGCCGAAACTGCTGATTTACTGGG 
               
               
                   
               
               
                 CAAGCACCCGCGAAAGTGGCGTGCCTGATCGCTTTAGTGGTAGCGGCAGCGGC 
               
               
                   
               
               
                 ACCGATTTTACCCTGACCATTAGCAGTCTGCAGGCCGAGGACGTTGCCGTTTAT 
               
               
                   
               
               
                 TACTGCCAGCAGTACTATAGCGCACCGCTGACATTTGGCGGTGGCACCAANGTG 
               
               
                   
               
               
                 GAAATTAAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 7 and 8): 
               
               
                 gatatccagatgacccagtccccgagctccctgtccgcctctgtgggcgatagggtcacc 
               
               
                  D  I  Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T 
               
               
                   
               
               
                 atcacctgccgggcgagccaggatgtgaccaccgctgtagcctggtatcaacagaaacca 
               
               
                  I  T  C  R  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P 
               
               
                   
               
               
                 ggaaaagctccgaagcttctgatttactgggcgagccgtcttcataatggcgtgccgagc 
               
               
                  G  K  A  P  K  L  L  I  Y  W  A  S  R  L  H  N  G  V  P  S 
               
               
                   
               
               
                 cgctttagcggcagcggctccgggacggatttcactctgaccatcagcagtctgcagccg 
               
               
                  R  F  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P 
               
               
                   
               
               
                 gaagacttcgcaacttattactgtcagcaacattatagcaccccgctgacgttcggacag 
               
               
                  E  D  F  A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q 
               
               
                   
               
               
                 ggtaccaaggtggagatcaaacgtacggtggcagcaccgagcgtgtttatctttccgccg 
               
               
                  G  T  K  V  E  I  K  R  T  V  A  A  P  S  V  F  I  F  P  P 
               
               
                   
               
               
                 agcgacgaacaactgaaaagtggcacagccagcgtggtgtgtttactgaacaacttctat 
               
               
                  S  D  E  Q  L  K  S  G  T  A  S  V  V  C  L  L  N  N  F  Y 
               
               
                   
               
               
                 cctcgcgaggccaaggtgcagtggaaagtggacaatgcactgcagagtggcaatagccag 
               
               
                  P  R  E  A  K  V  Q  W  K  V  D  N  A  L  Q  S  G  N  S  Q 
               
               
                   
               
               
                 gagagcgtgaccgaacaggatagcaaagatagcacctatagcctgagtagcaccctgacc 
               
               
                  E  S  V  T  E  Q  D  S  K  D  S  T  Y  S  L  S  S  T  L  T 
               
               
                   
               
               
                 ctgagcaaggccgattatgagaagcacaaggtgtatgcatgcgaggttacccatcagggc 
               
               
                  L  S  K  A  D  Y  E  K  H  K  V  Y  A  C  E  V  T  H  Q  G 
               
               
                   
               
               
                 ctgagcagcccggtgaccaaaagctttaaccgtggcgaatgcggtggtagtggtggatcc 
               
               
                  L  S  S  P  V  T  K  S  F  N  R  G  E  C  G  G  S  G  G  S 
               
               
                   
               
               
                 gccggtagcgcaggtagtgcaggtagtggcggcagcgaagttcagctgttagaaagtggc 
               
               
                  A  G  S  A  G  S  A  G  S  G  G  S  E  V  Q  L  L  E  S  G 
               
               
                   
               
               
                 ggtggtctggttaagccgggcggtagtctgcgcctgagctgtgcagcaagtggtttcacc 
               
               
                  G  G  L  V  K  P  G  G  S  L  R  L  S  C  A  A  S  G  F  T 
               
               
                   
               
               
                 ctgatcaattatcgtatgaactgggtgcgccaagccccgggtaaaggtctggagtgggtt 
               
               
                  L  I  N  Y  R  M  N  W  V  R  Q  A  P  G  K  G  L  E  W  V 
               
               
                   
               
               
                 agtagtatcagcagcagcagcagttacatccactatgccgatagcgttaagggccgcttt 
               
               
                  S  S  I  S  S  S  S  S  Y  I  H  Y  A  D  S  V  K  G  R  F 
               
               
                   
               
               
                 acaatcagccgcgataatgccgagaatagcttatacctgcaaatgaacagtctaagggcg 
               
               
                  T  I  S  R  D  N  A  E  N  S  L  Y  L  Q  M  N  S  L  R  A 
               
               
                   
               
               
                 gaagataccgccgtttactactgcgttcgtgaaggccctcgcgcaacaggctatagcatg 
               
               
                  E  D  T  A  V  Y  Y  C  V  R  E  G  P  R  A  T  G  Y  S  M 
               
               
                   
               
               
                 gcagacgtgttcgacatttggggtcagggcaccatggtgaccgttagtagcggcggtggt 
               
               
                  A  D  V  F  D  I  W  G  Q  G  T  M  V  T  V  S  S  G  G  G 
               
               
                   
               
               
                 ggtagtggtggtggcggtagtggtggcggtggcagcgaactggtgatgacccagagtccg 
               
               
                  G  S  G  G  G  G  S  G  G  G  G  S  E  L  V  M  T  Q  S  P 
               
               
                   
               
               
                 gatagcctggccgtgagcttaggcgagcgtgcaaccattaattgtaaaagcagtcagagt 
               
               
                  D  S  L  A  V  S  L  G  E  R  A  T  I  N  C  K  S  S  Q  S 
               
               
                   
               
               
                 gttctgtatagtagcaataacaagagctatctggcctggtatcagcagaagccgggccag 
               
               
                  V  L  Y  S  S  N  N  K  S  Y  L  A  W  Y  Q  Q  K  P  G  Q 
               
               
                   
               
               
                 ccgccgaaactgctgatttactgggcaagcacccgcgaaagtggcgtgcctgatcgcttt 
               
               
                  P  P  K  L  L  I  Y  W  A  S  T  R  E  S  G  V  P  D  R  F 
               
               
                   
               
               
                 agtggtagcggcagcggcaccgattttaccctgaccattagcagtctgcaggccgaggac 
               
               
                  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  A  E  D 
               
               
                   
               
               
                 gttgccgtttattactgccagcagtactatagcgcaccgctgacatttggcggtggcacc 
               
               
                  V  A  V  Y  Y  C  Q  Q  Y  Y  S  A  P  L  T  F  G  G  G  T 
               
               
                   
               
               
                 aangtggaaattaaa 
               
               
                  X  V  E  I  K 
               
               
                   
               
               
                 F4-KZ52 HC N′Fusion Sequence: 
               
               
                 Amino Acid (SEQ ID NO: 9): 
               
               
                 EVQLLESGGGLVKPGGSLRLSCAASGFTLINYRMNWVRQAPGKGLEWVSSISSSSS 
               
               
                   
               
               
                 YIHYADSVKGRFTISRDNAENSLYLQMNSLRAEDTAVYYCVREGPRATGYSMADV 
               
               
                   
               
               
                 FDIWGQGTMVTVSS GGGGSGGGGSGGGGS ELVMTQSPDSLAVSLGERATINCKSS 
               
               
                   
               
               
                 QSVLYSSNNKSYLAWYQQKPGQPPKLLIYWASTRESGVFDRFSGSGSGTDFTLTISS 
               
               
                   
               
               
                 LQAEDVAVYYCQQYYSAPLTFGGGTKVEIK GGSAGSAGSAGSGGS EVQLVESGG 
               
               
                   
               
               
                 GLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAYIKPGGGNTYYADS 
               
               
                   
               
               
                 VKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQLYGNSFFDYWGQGTLVTVS 
               
               
                   
               
               
                 S ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS   
               
               
                   
               
               
                 
                   GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCDKTHTCPPCPA 
                 
               
               
                   
               
               
                 
                   PELLGRPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK 
                 
               
               
                   
               
               
                 
                   PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT 
                 
               
               
                   
               
               
                 
                   LPPSREEMTKNQVSLTCLVKGFYPSDLAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL 
                 
               
               
                   
               
               
                 
                   TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 
                 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. Italicized region is CH1-CH3 for the HC and the CL region. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 10): 
                   
               
               
                 GAAGTTCAGTTACTGGAAAGTGGCGGCGGCCTGGTTAAACCGGGTGGTAGCCT 
               
               
                   
               
               
                 GCGTCTGAGTTGCGCAGCAAGCGGCTTCACCCTGATCAACTATCGCATGAACTG 
               
               
                   
               
               
                 GGTGCGCCAAGCACCGGGTAAGGGTCTGGAGTGGGTGAGCAGCATCAGCAGCA 
               
               
                   
               
               
                 GCAGCAGCTACATCCACTACGCAGACAGCGTTAAAGGCCGCTTCACCATTAGCC 
               
               
                   
               
               
                 GCGATAACGCCGAAAACAGCCTGTACCTGCAGATGAACAGTCTAAGGGCGGAG 
               
               
                   
               
               
                 GATACCGCAGTGTACTACTGCGTTCGTGAAGGCCCGCGTGCAACCGGCTATAGC 
               
               
                   
               
               
                 ATGGCCGACGTTTTTGATATTTGGGGCCAGGGCACCATGGTGACCGTGAGTAGT 
               
               
                   
               
               
                 GGTGGTGGTGGCAGCGGTGGTGGCGGTAGTGGTGGTGGTGGCAGTGAACTGGT 
               
               
                   
               
               
                 TATGACCCAGAGTCCGGACAGTCTGGCAGTGAGCCTGGGCGAGCGTGCAACCA 
               
               
                   
               
               
                 TCAACTGTAAGAGCAGTCAGAGCGTGCTGTATAGTAGCAACAATAAAAGCTAT 
               
               
                   
               
               
                 CTGGCGTGGTATCAGCAGAAGCCGGGTCAGCCGCCTAAGCTGCTGATTTATTGG 
               
               
                   
               
               
                 GCCAGCACCCGCGAAAGCGGTGTTCCGGATCGCTTTAGCGGTAGCGGCAGCGG 
               
               
                   
               
               
                 TACCGATTTCACCCTGACCATCAGCAGCCTGCAGGCCGAAGATGTGGCCGTGTA 
               
               
                   
               
               
                 TTATTGCCAGCAGTACTACAGCGCCCCGCTGACCTTTGGTGGCGGTACCAAGGT 
               
               
                   
               
               
                 GGAAATTAAAGGCGGCAGTGCCGGTAGTGCCGGTAGTGCAGGTAGCGGCGGTA 
               
               
                   
               
               
                 GCGAGGTTCAGCTGGTGGAAAGCGGCGGTGGTCTGGTTCAGCCTGGTGGTAGC 
               
               
                   
               
               
                 CTGCGCCTGAGCTGTGCCGCAAGCGGTTTCGCATTTAACTACTATGACATGTTCT 
               
               
                   
               
               
                 GGGTTCGCCAGGCACCGGGCAAAGGTCTGGAATGGGTGGCCTATATCAAACCG 
               
               
                   
               
               
                 GGCGGCGGCAACACCTACTACGCCGATAGCGTTAAGGGTCGTTTCACCATCAGC 
               
               
                   
               
               
                 GCCGATACCAGCAAAAACACCGCCTATCTGCAGATGAATAGCCTAAGGGCGGA 
               
               
                   
               
               
                 AGACACCGCAGTGTATTACTGCGCACGCCAGCTGTACGGCAACAGCTTTTTCGA 
               
               
                   
               
               
                 TTACTGGGGCCAGGGTACCCTGGTTACCGTGAGCAGC 
               
               
                   
               
               
                 Combined (SEQ ID NO: 9 and 10): 
               
               
                 gaagttcagttactggaaagtggcggcggcctggttaaaccgggtggtagcctgcgtctg 
               
               
                  E  V  Q  L  L  E  S  G  G  G  L  V  K  P  G  G  S  L  R  L 
               
               
                   
               
               
                 agttgcgcagcaagcggcttcaccctgatcaactatcgcatgaactgggtgcgccaagca 
               
               
                  S  C  A  A  S  G  F  T  L  I  N  Y  R  M  N  W  V  R  Q  A 
               
               
                   
               
               
                 ccgggtaagggtctggagtgggtgagcagcatcagcagcagcagcagctacatccactac 
               
               
                  P  G  K  G  L  E  W  V  S  S  I  S  S  S  S  S  Y  I  H  Y 
               
               
                   
               
               
                 gcagacagcgttaaaggccgcttcaccattagccgcgataacgccgaaaacagcctgtac 
               
               
                  A  D  S  V  K  G  R  F  T  I  S  R  D  N  A  E  N  S  L  Y 
               
               
                   
               
               
                 ctgcagatgaacagtctaagggcggaggataccgcagtgtactactgcgttcgtgaaggc 
               
               
                  L  Q  M  N  S  L  R  A  E  D  T  A  V  Y  Y  C  V  R  E  G 
               
               
                   
               
               
                 ccgcgtgcaaccggctatagcatggccgacgtttttgatatttggggccagggcaccatg 
               
               
                  P  R  A  T  G  Y  S  M  A  D  V  F  D  I  W  G  Q  G  T  M 
               
               
                   
               
               
                 gtgaccgtgagtagtggtggtggtggcagcggtggtggcggtagtggtggtggtggcagt 
               
               
                  V  T  V  S  S  G  G  G  G  S  G  G  G  G  S  G  G  G  G  S 
               
               
                   
               
               
                 gaactggttatgacccagagtccggacagtctggcagtgagcctgggcgagcgtgcaacc 
               
               
                  E  L  V  M  T  Q  S  P  D  S  L  A  V  S  L  G  E  R  A  T 
               
               
                   
               
               
                 atcaactgtaagagcagtcagagcgtgctgtatagtagcaacaataaaagctatctggcc 
               
               
                  I  N  C  K  S  S  Q  S  V  L  Y  S  S  N  N  K  S  Y  L  A 
               
               
                   
               
               
                 tggtatcagcagaagccgggtcagccgcctaagctgctgatttattgggccagcacccgc 
               
               
                  W  Y  Q  Q  K  P  G  Q  P  P  K  L  L  I  Y  W  A  S  T  R 
               
               
                   
               
               
                 gaaagcggtgttccggatcgctttagcggtagcggcagcggtaccgatttcaccctgacc 
               
               
                  E  S  G  V  P  D  R  F  S  G  S  G  S  G  T  D  F  T  L  T 
               
               
                   
               
               
                 atcagcagcctgcaggccgaagatgtggccgtgtattattgccagcagtactacagcgcc 
               
               
                  I  S  S  L  Q  A  E  D  V  A  V  Y  Y  C  Q  Q  Y  Y  S  A 
               
               
                   
               
               
                 ccgctgacctttggtggcggtaccaaggtggaaattaaaggcggcagtgccggtagtgcc 
               
               
                  P  L  T  F  G  G  G  T  K  V  E  I  K  G  G  S  A  G  S  A 
               
               
                   
               
               
                 ggtagtgcaggtagcggcggtagcgaggttcagctggtggaaagcggcggtggtctggtt 
               
               
                  G  S  A  G  S  G  G  S  E  V  Q  L  V  E  S  G  G  G  L  V 
               
               
                   
               
               
                 cagcctggtggtagcctgcgcctgagctgtgccgcaagcggtttcgcatttaactactat 
               
               
                  Q  P  G  G  S  L  R  L  S  C  A  A  S  G  F  A  F  N  Y  Y 
               
               
                   
               
               
                 gacatgttctgggttcgccaggcaccgggcaaaggtctggaatgggtggcctatatcaaa 
               
               
                  D  M  F  W  V  R  Q  A  P  G  K  G  L  E  W  V  A  Y  I  K 
               
               
                   
               
               
                 ccgggcggcggcaacacctactacgccgatagcgttaagggtcgtttcaccatcagcgcc 
               
               
                  P  G  G  G  N  T  Y  Y  A  D  S  V  K  G  R  F  T  I  S  A 
               
               
                   
               
               
                 gataccagcaaaaacaccgcctatctgcagatgaatagcctaagggcggaagacaccgca 
               
               
                  D  T  S  K  N  T  A  Y  L  Q  M  N  S  L  R  A  E  D  T  A 
               
               
                   
               
               
                 gtgtattactgcgcacgccagctgtacggcaacagctttttcgattactggggccagggt 
               
               
                  V  Y  Y  C  A  R  Q  L  Y  G  N  S  F  F  D  T  W  G  Q  G 
               
               
                   
               
               
                 accctggttaccgtgagcagc 
               
               
                  T  L  V  T  V  S  S 
               
               
                   
               
               
                 F4-KZ52 LC N′ Fusion Sequence 
               
               
                 Amino Acid (SEQ ID NO: 11): 
               
               
                 EVQLLESGGGLVKPGGSLRLSCAASGFTLINYRMNWVRQAPGKGLEWVSSISSSSS 
               
               
                   
               
               
                 YIHYADSVKGRFTISRDNAENSLYLQMNSLRAEDTAVYYCVREGPRATGYSMADV 
               
               
                   
               
               
                 FDIWGQGTMVTVSS GGGGSGGGGSGGGGS ELVMTQSPDSLAVSLGERATINCKSS 
               
               
                   
               
               
                 QSVLYSSNNKSYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISS 
               
               
                   
               
               
                 LQAEDVAVYYCQQYYSAPLTFGGGTKVEIK GGSAGSAGSAGSGGS DIQMTQSPSS 
               
               
                   
               
               
                 LSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYWASTRHTGVPSRFSGS 
               
               
                   
               
               
                 GSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQGTKVEIK RTVAAPSVFIFPPSDEQ   
               
               
                   
               
               
                 
                   LKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA 
                 
               
               
                   
               
               
                 
                   DYEKHKVYACEVTHQGLSSPVTKSFNRGECGGSDYKDDDDK 
                 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. Italicized region is CH1-CH3 for the HC and the CL region. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 12): 
                   
               
               
                 GAAGTTCAGTTACTGGAAAGTGGCGGCGGCCTGGTTAAACCGGGTGGTAGCCT 
               
               
                   
               
               
                 GCGTCTGAGTTGCGCAGCAAGCGGCTTCACCCTGATCAACTATCGCATGAACTG 
               
               
                   
               
               
                 GGTGCGCCAAGCACCGGGTAAGGGTCTGGAGTGGGTGAGCAGCATCAGCAGCA 
               
               
                   
               
               
                 GCAGCAGCTACATCCACTACGCAGACAGCGTTAAAGGCCGCTTCACCATTAGCC 
               
               
                   
               
               
                 GCGATAACGCCGAAAACAGCCTGTACCTGCAGATGAACAGTCTAAGGGCGGAG 
               
               
                   
               
               
                 GATACCGCAGTGTACTACTGCGTTCGTGAAGGCCCGCGTGCAACCGGCTATAGC 
               
               
                   
               
               
                 ATGGCCGACGTTTTTGATATTTGGGGCCAGGGCACCATGGTGACCGTGAGTAGT 
               
               
                   
               
               
                 GGTGGTGGTGGCAGCGGTGGTGGCGGTAGTGGTGGTGCTGGCAGTGAACTGGT 
               
               
                   
               
               
                 TATGACCCAGAGTCCGGACAGTCTGGCAGTGAGCCTGGGCGAGCGTGCAACCA 
               
               
                   
               
               
                 TCAACTGTAAGAGCAGTCAGAGCGTGCTGTATAGTAGCAACAATAAAAGCTAT 
               
               
                   
               
               
                 CTGGCCTGGTATCAGCAGAAGCCGGGTCAGCCGCCTAAGCTGCTGATTTATTGG 
               
               
                   
               
               
                 GCCAGACCCGCGAAAGCGGTGTTCCGGATCGCTTTAGCGGTAGCGGCAGCGG 
               
               
                   
               
               
                 TACCGATTTCACCCTGACCATCAGCAGCCTGCAGGCCGAAGATGTGGCCGTGTA 
               
               
                   
               
               
                 TTATTGCCAGCAGTACTACAGCGCCCCGCTGACCTTTGGTGGCGGTACCAAGGT 
               
               
                   
               
               
                 GGAAATTAAAGGCGGCAGTGCCGTAGTGCCGGTAGTGCAGGTAGCGGCGGTA 
               
               
                   
               
               
                 GCGATATCCAGATGACCCAGAGTCCGAGTAGTCTGAGCGCCAGCGTTGGTGAC 
               
               
                   
               
               
                 CGCGTTACCATCACCTGCAAGGCCAGCCAGGATGTTACCACCGCCGTGGCCTGG 
               
               
                   
               
               
                 TATCAACAGAAACCGGGCAAGGCCCCGAAGCTGCTGATTTATTGGGCCSGTAC 
               
               
                   
               
               
                 ACGCCATACAGGCGTGCCGAGCCGTTTTAGTGGCAGCGGTAGCGGTACCGACTT 
               
               
                   
               
               
                 CACCCTGACCATCAGTAGCCTGCAACCGGAGGATTTCGCGACCTACTACTGCCA 
               
               
                   
               
               
                 GCAGCACTACAGCACCCCGCTGACCTTTGGCCAAGGTACCAAGGTGGAGATTA 
               
               
                   
               
               
                 AG 
               
               
                   
               
               
                 Combined (SEQ ID NO: 11 and 12): 
               
               
                 gaagttcagttactggaaagtggcggcggcctggttaaaccgggtggtagcctgcgtctg 
               
               
                  E  V  Q  L  L  E  S  G  G  G  L  V  K  P  G  G  S  L  R  L 
               
               
                   
               
               
                 agttgcgcagcaagcggcttcaccctgatcaactatcgcatgaactgggtgcgccaagca 
               
               
                  S  C  A  A  S  G  F  T  L  I  N  Y  R  M  N  W  V  R  Q  A 
               
               
                   
               
               
                 ccgggtaagggtctggagtgggtgagcagcatcagcagcagcagcagctacatccactac 
               
               
                  P  G  K  G  L  E  W  V  S  S  I  S  S  S  S  S  Y  I  H  Y 
               
               
                   
               
               
                 gcagacagcgttaaaggccgcttcaccattagccgcgataacgccgaaaacagcctgtac 
               
               
                  A  D  S  V  K  G  R  F  T  I  S  R  D  N  A  E  N  S  L  Y 
               
               
                   
               
               
                 ctgcagatgaacagtctaagggcggaggataccgcagtgtactactgcgttcgtgaaggc 
               
               
                  L  Q  M  N  S  L  R  A  E  D  T  A  V  Y  Y  C  V  R  E  G 
               
               
                   
               
               
                 ccgcgtgcaaccggctatagcatggccgacgtttttgatatttggggccagggcaccatg 
               
               
                  P  R  A  T  G  Y  S  M  A  D  V  F  D  I  W  G  Q  G  T  M 
               
               
                   
               
               
                 gtgaccgtgagtagtggtggtggtggcagcggtggtggcggtagtggtggtggtggcagt 
               
               
                  V  T  V  S  S  G  G  G  G  S  G  G  G  G  S  G  G  G  G  S 
               
               
                   
               
               
                 gaactggttatgacccagagtccggacagtctggcagtgagcctgggcgagcgtgcaacc 
               
               
                  E  L  V  M  T  Q  S  P  D  S  L  A  V  S  L  G  E  R  A  T 
               
               
                   
               
               
                 atcaactgtaagagcagtcagagcgtgctgtatagtagcaacaataaaagctatctggcc 
               
               
                  I  N  C  K  S  S  Q  S  V  L  Y  S  S  N  N  K  S  Y  L  A 
               
               
                   
               
               
                 tggtatcagcagaagccgggtcagccgcctaagctgctgatttattgggccagcacccgc 
               
               
                  W  Y  Q  Q  K  P  G  Q  P  P  K  L  L  I  Y  W  A  S  T  R 
               
               
                   
               
               
                 gaaagcggtgttccggatcgctttagcggtagcggcagcggtaccgatttcaccctgacc 
               
               
                  E  S  G  V  P  D  R  F  S  G  S  G  S  G  T  D  F  T  L  T 
               
               
                   
               
               
                 atcagcagcctgcaggccgaagatgtggccgtgtattattgccagcagtactacagcgcc 
               
               
                  I  S  S  L  Q  A  E  D  V  A  V  Y  Y  C  Q  Q  Y  Y  S  A 
               
               
                   
               
               
                 ccgctgacctttggtggcggtaccaaggtggaaattaaaggcggcagtgccggtagtgcc 
               
               
                  P  L  T  F  G  G  G  T  K  V  E  I  K  G  G  S  A  G  S  A 
               
               
                   
               
               
                 ggtagtgcaggtagcggcggtagcgatatccagatgacccagagtccgagtagtctgagc 
               
               
                  G  S  A  G  S  G  G  S  D  I  Q  M  T  Q  S  P  S  S  L  S 
               
               
                   
               
               
                 gccagcgttggtgaccgcgttaccatcacctgcaaggccagccaggatgttaccaccgcc 
               
               
                  A  S  V  G  D  R  V  T  I  T  C  K  A  S  Q  D  V  T  T  A 
               
               
                   
               
               
                 gtggcctggtatcaacagaaaccgggcaaggccccgaagctgctgatttattgggccagt 
               
               
                  V  A  W  Y  Q  Q  K  P  G  K  A  P  K  L  L  I  Y  W  A  S 
               
               
                   
               
               
                 acacgccatacaggcgtgccgagccgttttagtggcagcggtagcggtaccgacttcacc 
               
               
                  T  R  H  T  G  V  P  S  R  F  S  G  S  G  S  G  T  D  F  T 
               
               
                   
               
               
                 ctgaccatcagtagcctgcaaccggaggatttcgccacctactactgccagcagcactac 
               
               
                  L  T  I  S  S  L  Q  P  E  D  F  A  T  Y  Y  C  Q  Q  H  Y 
               
               
                   
               
               
                 agcaccccgctgacctttggccaaggtaccaaggtggagattaag 
               
               
                  S  T  P  L  T  F  G  Q  G  T  K  V  E  I  K 
               
               
                   
               
               
                 F4-KZ52 HC C′ Fusion Sequence: 
               
               
                 Amino Acid (SEQ ID NO: 13): 
               
               
                 EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEW 
               
               
                   
               
               
                 VAYIKPGGGNTYYADSVKGFTISADTSKNTAYLQMNSLRAEDTAVYYCARQLYG 
               
               
                   
               
               
                 NSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS 
               
               
                   
               
               
                 WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDK 
               
               
                   
               
               
                 KVEPKSCDKFHTCDKTHFCPPCPAPELLGRPSVFLFPPKPKDTLMISRTPEVTCVVV 
               
               
                   
               
               
                 DVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE 
               
               
                   
               
               
                 YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS 
               
               
                   
               
               
                 DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE 
               
               
                   
               
               
                 ALHNHYTQKSLSLSPGK GGSAGSAGSAGSGGS EVQLLESGGGLVKPGGSLRLSCA 
               
               
                   
               
               
                 ASGFTLINYRMNWVRQAPGKGLEWVSSISSSSSYIHYADSVKGRFTISRDNAENSLY 
               
               
                   
               
               
                 LQMNSLRAEDTAVYYCVREGPRATGYSMADVFDIWGQGTMVTVSS GGGGSGGG   
               
               
                   
               
               
                   GSGGGGS ELVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKSYLAWYQQKPGQP 
               
               
                   
               
               
                 PKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSAPLTFGG 
               
               
                   
               
               
                 GTKVEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker poly peptide. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 14): 
                   
               
               
                 GAAGTTCAACTGGTTGAGAGTGGCGGTGGCTTAGTTCAACCGGGCGGTAGTTTA 
               
               
                   
               
               
                 CGCCTGAGTTGTGCAGCCAGCGGTTTCGCCTTCAACTATTATGACATGTTTTGGG 
               
               
                   
               
               
                 TGCGCCAGGCACCGGGTAAAGGCCTGGAGTGGGTGGCCTATATCAAACCXGGGC 
               
               
                   
               
               
                 GGTGGCAACACCTATTACGCCGATAGCGTGAAAGGTCGCTTTACCATCAGCGCA 
               
               
                   
               
               
                 GATACCAGCAAGAATACCGCCTACCTGCAGATGAATAGCCTGCGTGCCGAAGA 
               
               
                   
               
               
                 CACCGCCGTTTATATTGCGCCCGCCAGCTGTACGGCAATAGCTTTTTCGATTAC 
               
               
                   
               
               
                 TGGGGCCAGGGCACCCTGGTTACCGTTAGCAGCGCTAGCACCAAGGGTCCGAG 
               
               
                   
               
               
                 CGTGTTTCCTCTGGCACCTAGCAGTAAAAGCACCAGTGGTGGTACAGCAGCCCT 
               
               
                   
               
               
                 GGGTTGCCTGGTGAAGGATTACTTTCCGGAGCCGGTGACCGTTAGTTGGAATAG 
               
               
                   
               
               
                 CGGCGCCCTGACCAGTGGCGTTCATACATTTCCGGCCGTGCTGCAGAGTAGTGG 
               
               
                   
               
               
                 CCTGTACAGCCTGAGTAGCGTTGTlACCGTTCCGAGCAGCAGCCTGGGCACCCA 
               
               
                   
               
               
                 GACCTATATTTGCAATGTTAACCATAAACCGAGCAACACAAAAGTTGATAAAA 
               
               
                   
               
               
                 AAGTTGAACCGAAGAGCTGTGACAAAACCCATACATGTGACAAAACACACACC 
               
               
                   
               
               
                 TGCCCGCCTTGTCCGGCACCTGAGCTCGTGGGTCGCCCGAGCGTTTTTCTGTTTC 
               
               
                   
               
               
                 CTCCGAAACCGAAAGACACCCTGATGATCAGCCGCACACCTGAGGTGACCTGT 
               
               
                   
               
               
                 GTTGTGGTGGATGTGAGCCACGAAGATCCTGAAGTTAAGTTTAACTGGTATGTG 
               
               
                   
               
               
                 GATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGTGAAGAGCAGTACAA 
               
               
                   
               
               
                 CAGCACCTATCGTGTTGTTAGTGTGCTGACCGTTCTGCACCAAGATTGGCTGAA 
               
               
                   
               
               
                 CGGCAAGGAGTATAAATGCAAGGTTAGCAATAAAGCCCTGCCGGCCGCGATCG 
               
               
                   
               
               
                 AGAAGACCATCAGCAAAGCCAAAGGTCAGCCGCGTGAGCCTCAGGTGTATACA 
               
               
                   
               
               
                 CTGCCGCCTAGCCGTGAGGAGATGACCAAGAATCAGGTTAGCCIGACCTGTCTG 
               
               
                   
               
               
                 GTGAAAGGCTTTTACCCGAGCGATATCGCCGTTGAGTGGGAAAGCAATGGTCA 
               
               
                   
               
               
                 GCCTGAGAACAACTACAAGACCACCCCGCCTGTTTTAGACAGTGATGGTAGCTT 
               
               
                   
               
               
                 TTTCTTATACAGCAAACTGACCGTTGATAAGAGCCGCTGGCAGCAGGGCAATGT 
               
               
                   
               
               
                 GTTTAGCTGCAGTGTTATGCATGAGGCCCTGCATAACCACTATACCCAGAAGAG 
               
               
                   
               
               
                 TCTGAGCCTGAGTCCTGGCAAAGGTGGATCCGCCGGTAGCGCAGGTAGTGCAG 
               
               
                   
               
               
                 GTAGTGGCGGCAGCGAAGTTCAGCTGTTAGAAAGTGGCGGTGGTCTGGTTAAG 
               
               
                   
               
               
                 CCGGGCGGTAGTCTGCGCCTGAGCTGTGCAGCAAGTGGTTTCACCCTGATCAAT 
               
               
                   
               
               
                 TATCGTATGAACTGGGTGCGCCAAGCCCCGGGTAAAGGTCTGGAGTGGGTTAGT 
               
               
                   
               
               
                 AGTATCAGCAGCAGCAGCAGTTACATCCACTATGCCGATAGCGTTAAGGGCCG 
               
               
                   
               
               
                 CTTTACAATCAGCCGCGATAATGCCGAGAATAGCTTATACCTGCAAATGAACAG 
               
               
                   
               
               
                 TCTAAGGGCGGAAGATACCGCCGTTTACTACTGCGTTCGTGAAGGCCCTCGCGC 
               
               
                   
               
               
                 AACAGGCTATAGCATGGCAGACGTGTTCGACATTTGGGGTCAGGGGACCATGG 
               
               
                   
               
               
                 TGACCGTTAGTAGCGGCGGTGGTGGTAGTGGTGGTGGCGGTAGTGGTGGCGGT 
               
               
                   
               
               
                 GGCAGCGAACTGGTGATGACCCAGAGTCCGGATAGCCTGGCCGTGAGCTTAGG 
               
               
                   
               
               
                 CGAGCGTGCAACCATTAATTGTAAAAGCAGTCAGAGTGTTCTGTATAGTAGCAA 
               
               
                   
               
               
                 TAACAAGAGCTATCTGGCCTGGTATCAGCAGAAGCCGGGCCAGCCGCCGAAAC 
               
               
                   
               
               
                 TGCTGATTTACTGGGCAAGCACCCGCGAAAGTGGCGTGCCTGATCGCTTTAGTG 
               
               
                   
               
               
                 GTAGCGGCAGCGGCACCGATTTTACCCTGACCATTAGCAGTCTGCAGGCCGAGG 
               
               
                   
               
               
                 ACGTTGCCGTTTATTACTGCCAGCAGTACTATAGCGCACCGCTGACATTTGGCG 
               
               
                   
               
               
                 GTGGCACCAAGGTGGAAATTAAATAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 13 and 14): 
               
               
                 gaagttcaactggttgagagtggcggtggcttagttcaaccgggcggtagtttacgcctg 
               
               
                  E  V  Q  L  V  E  S  G  G  G  L  V  Q  P  G  G  S  L  R  L 
               
               
                   
               
               
                 agttgtgcagccagcggtttcgccttcaactattatgacatgttttgggtgcgccaggca 
               
               
                  S  C  A  A  S  G  F  A  F  N  Y  Y  D  M  F  W  V  R  Q  A 
               
               
                   
               
               
                 ccgggtaaaggcctggagtgggtggcctatatcaaaccgggcggtggcaacacctattac 
               
               
                  P  G  K  G  L  E  W  V  A  Y  I  K  P  G  G  G  N  T  Y  Y 
               
               
                   
               
               
                 gccgatagcgtgaaaggtcgctttaccatcagcgcagataccagcaagaataccgcctac 
               
               
                  A  D  S  V  K  G  R  F  T  I  S  A  D  T  S  K  N  T  A  Y 
               
               
                   
               
               
                 ctgcagatgaatagcctgcgtgccgaagacaccgccgtttattattgcgcccgccagctg 
               
               
                  L  Q  M  N  S  L  R  A  E  D  T  A  V  Y  Y  C  A  R  Q  L 
               
               
                   
               
               
                 tacggcaatagctttttcgattactggggccagggcaccctggttaccgttagcagcgct 
               
               
                  Y  G  N  S  F  F  D  Y  W  G  Q  G  T  L  V  T  V  S  S  A 
               
               
                   
               
               
                 agcaccaagggtccgagcgtgtttcctctggcacctagcagtaaaagcaccagtggtggt 
               
               
                  S  T  K  G  P  S  V  F  P  L  A  P  S  S  K  S  T  S  G  G 
               
               
                   
               
               
                 acagcagccctgggttgcctggtgaaggattactttccggagccggtgaccgttagttgg 
               
               
                  T  A  A  L  G  C  L  V  K  D  Y  F  P  E  P  V  T  V  S  W 
               
               
                   
               
               
                 aatagcggcgccctgaccagtggcgttcatacatttccggccgtgctgcagagtagtggc 
               
               
                  N  S  G  A  L  T  S  G  V  H  T  F  P  A  V  L  Q  S  S  G 
               
               
                   
               
               
                 ctgtacagcctgagtagcgttgttaccgttccgagcagcagcctgggcacccagacctat 
               
               
                  L  Y  S  L  S  S  V  V  T  V  P  S  S  S  L  G  T  Q  T  Y 
               
               
                   
               
               
                 atttgcaatgttaaccataaaccgagcaacacaaaagttgataaaaaagttgaaccgaag 
               
               
                  I  C  N  V  N  H  K  P  S  N  Y  K  V  D  K  K  V  E  P  K 
               
               
                   
               
               
                 agctgtgacaaaacccatacatgtgacaaaacacacacctgcccgccttgtccggcacct 
               
               
                  S  C  D  K  T  H  T  C  D  K  T  H  T  C  P  P  C  P  A  P 
               
               
                   
               
               
                 gagctgctgggtcgcccgagcgtttttctgtttcctccgaaaccgaaagacaccctgatg 
               
               
                  E  L  L  G  R  P  S  V  F  L  F  P  P  K  P  K  D  T  L  M 
               
               
                   
               
               
                 atcagccgcacacctgaggtgacctgtgttgtggtggatgtgagccacgaagatcctgaa 
               
               
                  I  S  R  T  P  E  V  T  C  V  V  V  D  V  S  H  E  D  P  E 
               
               
                   
               
               
                 gttaagtttaactggtatgtggatggcgtggaggtgcataatgccaagacaaagccgcgt 
               
               
                  V  K  F  N  W  Y  V  D  G  V  E  V  H  N  A  K  T  K  P  R 
               
               
                   
               
               
                 gaagagcagtacaacagcacctatcgtgttgttagtgtgctgaccgttctgcaccaagat 
               
               
                  E  E  Q  Y  N  S  T  Y  R  V  V  S  V  L  T  V  L  H  Q  D 
               
               
                   
               
               
                 tggctgaacggcaaggagtataaatgcaaggttagcaataaagccctgccggccccgatc 
               
               
                  W  L  N  G  K  E  Y  K  C  K  V  S  N  K  A  L  P  A  P  I 
               
               
                   
               
               
                 gagaagaccatcagcaaagccaaaggtcagccgcgtgagcctcaggtgtatacactgccg 
               
               
                  E  K  T  I  S  K  A  K  G  Q  P  R  E  P  Q  V  Y  T  L  P 
               
               
                   
               
               
                 cctagccgtgaggagatgaccaagaatcaggttagcctgacctgtctggtgaaaggcttt 
               
               
                  P  S  R  E  E  M  T  K  N  Q  V  S  L  T  C  L  V  K  G  F 
               
               
                   
               
               
                 tacccgagcgatatcgccgttgagtgggaaagcaatggtcagcctgagaacaactacaag 
               
               
                  Y  P  S  D  I  A  V  E  W  E  S  N  G  Q  P  E  N  N  Y  K 
               
               
                   
               
               
                 accaccccgcctgttttagacagtgatggtagctttttcttatacagcaaactgaccgtt 
               
               
                  T  T  P  P  V  L  D  S  D  G  S  F  F  L  Y  S  K  L  T  V 
               
               
                   
               
               
                 gataagagccgctggcagcagggcaatgtgtttagctgcagtgttatgcatgaggccctg 
               
               
                  D  K  S  R  W  Q  Q  G  N  V  F  S  C  S  V  M  H  E  A  L 
               
               
                   
               
               
                 cataaccactatacccagaagagtctgagcctgagtcctggcaaaggtggatccgccggt 
               
               
                  H  N  H  Y  T  Q  K  S  L  S  L  S  P  G  K  G  G  S  A  G 
               
               
                   
               
               
                 agcgcaggtagtgcaggtagtggcggcagcgaagttcagctgttagaaagtggcggtggt 
               
               
                  S  A  G  S  A  G  S  G  G  S  E  V  Q  L  L  E  S  G  G  G 
               
               
                   
               
               
                 ctggttaagccgggcggtagtctgcgcctgagctgtgcagcaagtggtttcaccctgatc 
               
               
                  L  V  K  P  G  G  S  L  R  L  S  C  A  A  S  G  F  T  L  I 
               
               
                   
               
               
                 aattatcgtatgaactgggtgcgccaagccccgggtaaaggtctggagtgggttagtagt 
               
               
                  N  Y  R  M  N  W  V  R  Q  A  P  G  K  G  L  E  W  V  S  S 
               
               
                   
               
               
                 atcagcagcagcagcagttacatccactatgccgatagcgttaagggccgctttacaatc 
               
               
                  I  S  S  S  S  S  Y  I  H  T  A  D  S  V  K  G  R  F  T  I 
               
               
                   
               
               
                 agccgcgataatgccgagaatagcttatacctgcaaatgaacagtctaagggcggaagat 
               
               
                  S  R  D  N  A  E  N  S  L  Y  L  Q  M  N  S  L  R  A  E  D 
               
               
                   
               
               
                 accgccgtttactactgcgttcgtgaaggccctcgcgcaacaggctatagcatggcagac 
               
               
                  T  A  V  Y  Y  C  V  R  E  G  P  R  A  T  G  Y  S  M  A  D 
               
               
                   
               
               
                 gtgttcgacatttggggtcagggcaccatggtgaccgttagtagcggcggtggtggtagt 
               
               
                  V  F  D  I  W  G  Q  G  T  M  V  T  V  S  S  G  G  G  G  S 
               
               
                   
               
               
                 ggtggtggcggtagtggtggcggtggcagcgaactggtgatgacccagagtccggatagc 
               
               
                  G  G  G  G  S  G  G  G  G  S  E  L  V  M  T  Q  S  P  D  S 
               
               
                   
               
               
                 ctggccgtgagcttaggcgagcgtgcaaccattaattgtaaaagcagtcagagtgttctg 
               
               
                  L  A  V  S  L  G  E  R  A  T  I  N  C  K  S  S  Q  S  V  L 
               
               
                   
               
               
                 tatagtagcaataacaagagctatctggcctggtatcagcagaagccgggccagccgccg 
               
               
                  Y  S  S  N  N  K  S  Y  L  A  W  Y  Q  Q  K  P  G  Q  P  P 
               
               
                   
               
               
                 aaactgctgatttactgggcaagcacccgcgaaagtggcgtgcctgatcgctttagtggt 
               
               
                  K  L  L  I  Y  W  A  S  T  R  E  S  G  V  P  D  R  F  S  G 
               
               
                   
               
               
                 agcggcagcggcaccgattttaccctgaccattagcagtctgcaggccgaggacgttgcc 
               
               
                  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  A  E  D  V  A 
               
               
                   
               
               
                 gtttattactgccagcagtactatagcgcaccgctgacatttggcggtggcaccaaggtg 
               
               
                  V  Y  Y  C  Q  Q  Y  Y  S  A  P  L  T  F  G  G  G  T  K  V 
               
               
                   
               
               
                 gaaattaaataa 
               
               
                  E  I  K  -  
               
               
                   
               
               
                 F4-KZ52 LC C′ Fusion Sequence: 
               
               
                 Amino Acid (SEQ ID NO: 15): 
               
               
                 DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIY 
               
               
                   
               
               
                 WASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQGTKVEI 
               
               
                   
               
               
                 KRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQES 
               
               
                   
               
               
                 VTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGS G   
               
               
                   
               
               
                   GSAGSAGSAGSGGS EVQLLESGGGLVKPGGSLRLSCAASGFTLINYRMNWVRQAP 
               
               
                   
               
               
                 GKGLEWVSSISSSSSYIHYADSVKGRFTISRDNAENSLYLQMNSLRAEDTAVYYCV 
               
               
                   
               
               
                 REGPRATGYSMADVFDIWGQGTMVTVSS GGGGSGGGGSGGGGS ELVMTQSPPSL 
               
               
                   
               
               
                 AVSLGERATINCKSSQSVLYSSNNKSYLAWYQQKPGQPPKLLIYWASTRESGVPDR 
               
               
                   
               
               
                 FSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSAPLTFGGGTKVEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 16): 
                   
               
               
                 GACATTCAGATGACCCAAAGTCCGAGCAGCCTGAGTGCCAGTGTTGGTGATCGC 
               
               
                   
               
               
                 GTGACAATCACATGCAAGGCCAGTCAGGACGTGACCACCGCAGTGGCCTGGTA 
               
               
                   
               
               
                 TCAGCAGAAACCGGGTAAGGCCCCGAAGCTGCTGATCTATTGGGCCAGTACCC 
               
               
                   
               
               
                 GCCACACCGGTGTTCCTAGTCGCTTCAGTGGCAGTGGCAGCGGCACAGATTTCA 
               
               
                   
               
               
                 CCCTGACCATCAGCAGCCTGCAACCGGAAGATTTTGCCACCTACTACTGCCAGC 
               
               
                   
               
               
                 AGCACTATAGCACCCCGCTGACCTTTGGCCAGGGCACCAAGGTTGAGATTAAAC 
               
               
                   
               
               
                 GTACGGTGGCAGCACCGAGCGTGTTTATCTTTCCGCCGAGCGACGAACAACTGA 
               
               
                   
               
               
                 AAAGTGGCACAGCCAGCGTGGTGTGTTTACTGAACAACTTCTATCCTCGCGAGG 
               
               
                   
               
               
                 CCAAGGTGCAGTGGAAAGTGGACAATGCACTGCAGAGTGGCAATAGCCAGGAG 
               
               
                   
               
               
                 AGCGTGACCGAACAGGATAGCAAAGATAGCACCTATAGCCTGAGTAGCACCCT 
               
               
                   
               
               
                 GACCCTGAGCAAGGCCGATTATGAGAAGCACAAGGTGTATGCATGCGAGGTTA 
               
               
                   
               
               
                 CCCATCAGGGCCTGAGCAGCCCGGTGACCAAAAGCTTTAACCGTGGCGAATGC 
               
               
                   
               
               
                 GGTGGTAGTGGTGGATCCGCCGGTAGCGCAGGTAGTGCAGGTAGTGGCGGCAG 
               
               
                   
               
               
                 CGAAGTTCAGCTGTTAGAAAGTGGCGGTGGTCTGGTTAAGCCGGGCGGTAGTCT 
               
               
                   
               
               
                 GCGCCTGAGCTGTGCAGCAAGTGGTTTCACCCTGATCAATTATCGTATGAACTG 
               
               
                   
               
               
                 GGTGCGCCAAGCCCCGGGTAAAGGTCTGGAGTGGGTTAGTAGTATCAGCAGCA 
               
               
                   
               
               
                 GCAGCAGTTACATCCACTATGCCGATAGCGTTAAGGGCCGCTTTACAATCAGCC 
               
               
                   
               
               
                 GCGATAATGCCGAGAATAGCTTATACCTGCAAATGAACAGTCTAAGGGCGGAA 
               
               
                   
               
               
                 GATACCGCCGTTTACTACTGCGTTCGTGAAGGCCCTCGCGCAACAGGCTATAGC  
               
               
                   
               
               
                 ATGGCAGACGTGTTCGACATTTGGGGTCAGGGCACCATGGTGACCGTTAGTAGC 
               
               
                   
               
               
                 GGCGGTGGTGGTAGTGGTGGTGGCGGTAGTGGTGGCGGTGGCAGCGAACTGGT 
               
               
                   
               
               
                 GATGACCCAGAGTCCGGATAGCCTGGCCGTGAGCTTAGGCGAGCGTGCAACCA 
               
               
                   
               
               
                 TTAATTGTAAAAGCAGTCAGAGTGTTCTGTATAGTAGCAATAACAAGAGCTATC 
               
               
                   
               
               
                 TGGCCTGGTATCAGCAGAAGCCGGGCCAGCCGCCGAAACTGCTGATTTACTGG 
               
               
                   
               
               
                 GCAAGCACCCGCGAAAGTGGCGTGCCTGATCGCTTTAGTGGTAGCGGCAGCGG 
               
               
                   
               
               
                 CACCGATTTTACCCTGACCATTAGCAGTCTGCAGGCCGAGGACGTTGCCGTTTA 
               
               
                   
               
               
                 TTACTGCCAGCAGTACTATAGCGCACCGCTGACATTTGGCGGTGGCACCAAGGT 
               
               
                   
               
               
                 GGAAATTAAATAA  
               
               
                   
               
               
                 Combined (SEQ ID NO: 15 and 16): 
               
               
                 gacattcagatgacccaaagtccgagcagcctgagtgccagtgttggtgatcgcgtgaca 
               
               
                  D  I  Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T 
               
               
                   
               
               
                 atcacatgcaaggccagtcaggacgtgaccaccgcagtggcctggtatcagcagaaaccg 
               
               
                  I  T  C  K  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P 
               
               
                   
               
               
                 ggtaaggccccgaagctgctgatctattgggccagtacccgccacaccggtgttcctagt 
               
               
                  G  K  A  P  K  L  L  I  Y  W  A  S  T  R  H  T  G  V  P  S 
               
               
                   
               
               
                 cgcttcagtggcagtggcagcggcacagatttcaccctgaccatcagcagcctgcaaccg 
               
               
                  R  F  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P 
               
               
                   
               
               
                 gaagattttgccacctactactgccagcagcactatagcaccccgctgacctttggccag 
               
               
                  E  D  F  A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q 
               
               
                   
               
               
                 ggcaccaaggttgagattaaacgtacggtggcagcaccgagcgtgtttatctttccgccg 
               
               
                  G  T  K  V  E  I  K  R  T  V  A  A  P  S  V  F  I  F  P  P 
               
               
                   
               
               
                 agcgacgaacaactgaaaagtggcacagccagcgtggtgtgtttactgaacaacttctat 
               
               
                  S  D  E  Q  L  K  S  G  T  A  S  V  V  C  L  L  N  N  F  Y 
               
               
                   
               
               
                 cctcgcgaggccaaggtgcagtggaaagtggacaatgcactgcagagtggcaatagccag 
               
               
                  P  R  E  A  K  V  Q  W  K  V  D  N  A  L  Q  S  G  N  S  Q 
               
               
                   
               
               
                 gagagcgtgaccgaacaggatagcaaagatagcacctatagcctgagtagcaccctgacc 
               
               
                  E  S  V  T  E  Q  D  S  K  D  S  T  Y  S  L  S  S  T  L  T 
               
               
                   
               
               
                 ctgagcaaggccgattatgagaagcacaaggtgtatgcatgcgaggttacccatcagggc 
               
               
                  L  S  K  A  D  Y  E  K  H  K  V  Y  A  C  E  V  T  H  Q  G 
               
               
                   
               
               
                 ctgagcagcccggtgaccaaaagctttaaccgtggcgaatgcggtggtagtggtggatcc 
               
               
                  L  S  S  P  V  T  K  S  F  N  R  G  E  C  G  G  S  G  G  S 
               
               
                   
               
               
                 gccggtagcgcaggtagtgcaggtagtggcggcagcgaagttcagctgttagaaagtggc 
               
               
                  A  G  S  A  G  S  A  G  S  G  G  S  E  V  Q  L  L  E  S  G 
               
               
                   
               
               
                 ggtggtctggttaagccgggcggtagtctgcgcctgagctgtgcagcaagtggtttcacc 
               
               
                  G  G  L  V  K  P  G  G  S  L  R  L  S  C  A  A  S  G  F  T 
               
               
                   
               
               
                 ctgatcaattatcgtatgaactgggtgcgccaagccccgggtaaaggtctggagtgggtt 
               
               
                  L  I  N  Y  R  M  N  W  V  R  Q  A  P  G  K  G  L  E  W  V 
               
               
                   
               
               
                 agtagtatcagcagcagcagcagttacatccactatgccgatagcgttaagggccgcttt 
               
               
                  S  S  I  S  S  S  S  S  Y  I  H  Y  A  D  S  V  K  G  R  F 
               
               
                   
               
               
                 acaatcagccgcgataatgccgagaatagcttatacctgcaaatgaacagtctaagggcg 
               
               
                  T  I  S  R  D  N  A  E  N  S  L  Y  L  Q  M  N  S  L  R  A 
               
               
                   
               
               
                 gaagataccgccgtttactactgcgttcgtgaaggccctcgcgcaacaggctatagcatg 
               
               
                  E  D  T  A  V  Y  Y  C  V  R  E  G  P  R  A  T  G  Y  S  M 
               
               
                   
               
               
                 gcagacgtgttcgacatttggggtcagggcaccatggtgaccgttagtagcggcggtggt 
               
               
                  A  D  V  F  D  I  W  G  Q  G  T  M  V  T  V  S  S  G  G  G 
               
               
                   
               
               
                 ggtagtggtggtggcggtagtggtggcggtggcagcgaactggtgatgacccagagtccg 
               
               
                  G  S  G  G  G  G  S  G  G  G  G  S  E  L  V  M  T  Q  S  P 
               
               
                   
               
               
                 gatagcctggccgtgagcttaggcgagcgtgcaaccattaattgtaaaagcagtcagagt 
               
               
                  D  S  L  A  V  S  L  G  E  R  A  T  I  N  C  K  S  S  Q  S 
               
               
                   
               
               
                 gttctgtatagtagcaataacaagagctatctggcctggtatcagcagaagccgggccag 
               
               
                  V  L  Y  S  S  N  N  K  S  Y  L  A  W  Y  Q  Q  K  P  G  Q 
               
               
                   
               
               
                 ccgccgaaactgctgatttactgggcaagcacccgcgaaagtggcgtgcctgatcgcttt 
               
               
                  P  P  K  L  L  I  Y  W  A  S  T  R  E  S  G  V  P  D  R  F 
               
               
                   
               
               
                 agtggtagcggcagcggcaccgattttaccctgaccattagcagtctgcaggccgaggac 
               
               
                  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  A  E  D 
               
               
                   
               
               
                 gttgccgtttattactgccagcagtactatagcgcaccgctgacatttggcggtggcacc 
               
               
                  V  A  V  Y  Y  C  Q  Q  Y  Y  S  A  P  L  T  F  G  G  G  T 
               
               
                   
               
               
                 aaggtggaaattaaataa 
               
               
                  K  V  E  I  K  - 
               
               
                   
               
               
                 F4-2G4 LC N′ Fusion Sequence: 
               
               
                 Amino acid (SEQ ID NO: 17): 
               
               
                 EVQLQESGGGLMQPGGSMKLSCVASGFTFSNYWMNWVRQSPEKGLEWVAEIRLK 
               
               
                   
               
               
                 SNNYATHYAESVKGRFTISRDDSKRSVYLQMNTLRAEDTGIYYCTRGNGNYRAMDYWGQGT 
               
               
                   
               
               
                 SVTVSS GGGGSGGGGSGGGGS DIQMTQSPASLSVSVGETVSITCRASENIYSSLAWYQQKQ 
               
               
                   
               
               
                 GKSPQLLVYSATILADGVPSRFSGSGSGTQYSLKINSLQSEDFGTYYCQHFWGTPYTFGGG 
               
               
                   
               
               
                 TKLEIK GGSAGSAGSAGSGGS DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKP 
               
               
                   
               
               
                 GKAPKLLIYWASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQG 
               
               
                   
               
               
                 TKVEIK 
               
               
                   
               
               
                 Underlined region is glycine-rich linker polypeptide. Bold region 
               
               
                 is fusion linker polypeptide. 
               
               
                 Nucleotide (SEQ ID NO: 18): 
               
               
                 GAAGTTCAGCTGCAGGAAAGCGGCGGTGGTCTGATGCAGCCTGGTGGCAGCATG 
               
               
                   
               
               
                 AAACTGAGCTGTGTGGCCAGCGGTTTCACCTTCAGCAACTATTGGATGAACTGGGTGCGTC 
               
               
                   
               
               
                 AGAGTCCGGAAAAAGGCCTGGAATGGGTTGCCGAGATCCGCCTGAAGAGTAACAACTATGC 
               
               
                   
               
               
                 CACCCATTACGCCGAGAGCGTGAAAGGTCGCTTTACCATCAGCCGTGATGACAGCAAACGC 
               
               
                   
               
               
                 AGCGTGTATCTGCAGATGAACACATTACGTGCTGAAGACACCGGTATCTACTATTGCACCC 
               
               
                   
               
               
                 GCGGCAACGGCAACTATCGCGCCATGGATTATTGGGGCCAGGGTACCAGCGTGACCGTTAG 
               
               
                   
               
               
                 TAGCGGCGGCGGTGGTAGTGGTGGTGGTGGTAGTGGCGGTGGCGGTAGCGACATTCAAATG 
               
               
                   
               
               
                 ACCCAGAGTCCTGCAAGCCTGAGCGTGAGCGTGGGTGAGACCGTGAGCATCACATGCGGCG 
               
               
                   
               
               
                 CCAGCGAGAACATTTATAGCAGCCTGGCCTGGTACCAGCAAAAACAGGGTAAAAGCCCGCA 
               
               
                   
               
               
                 GCTGCTGGTGTATAGCGCCACCATTCTGGCAGATGGTGTGCCGAGCCGTTTTAGTGGCAGT 
               
               
                   
               
               
                 GGCAGTGGTACCCAGTACAGCCTGAAAATCAACAGCCTGCAGAGCGAAGACTTCGGCACCT 
               
               
                   
               
               
                 ACTACTGTCAGCACTTTTGGGGCACCCCGTATACCTTTGGCGGCGGTACCAAGCTGGAAAT 
               
               
                   
               
               
                 CAAAGGTGGATCCGCAGGTAGCGCAGGCAGTGCAGGCAGCGGTGGTAGCGATATCCAGATG 
               
               
                   
               
               
                 ACCCAAAGCCCGAGCAGCTTAAGTGCCAGCGTGGGCGATCGCGTGACCATCACCTGCAAAG 
               
               
                   
               
               
                 CCAGTCAGGACGTTACCACAGCCGTGGCCTGGTATCAGCAGAAACCGGGTAAAGCCCCTAA 
               
               
                   
               
               
                 GCTGCTGATCTATTGGGCCAGCACCCGCCACACAGGTGTTCCGAGTCGTTTCAGCGGCAGC 
               
               
                   
               
               
                 GGTAGCGGTACCGATTTTACCCTGACCATCAGCAGCCTGCAGCCGGAAGACTTCGCAACAT 
               
               
                   
               
               
                 ACTACTGCCAGCAGCACTATTCTACCCCGCTGACATTCGGCCAGGGCACAAAAGTGGAGAT 
               
               
                   
               
               
                 TAAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 17 and 18): 
               
               
                 gaagttcagctgcaggaaagcggcggtggtctgatgcagcctggtggcagcatgaaactg 
               
               
                  E  V  Q  L  Q  E  S  G  G  G  L  M  Q  P  G  G  S  M  K  L 
               
               
                   
               
               
                 agctgtgtggccagcggtttcaccttcagcaactattggatgaactgggtgcgtcagagt 
               
               
                  S  C  V  A  S  G  F  T  F  S  N  Y  W  M  N  W  V  R  Q  S 
               
               
                   
               
               
                 ccggaaaaaggcctggaatgggttgccgagatccgcctgaagagtaacaactatgccacc 
               
               
                  P  E  K  G  L  E  W  V  A  E  I  R  L  K  S  N  N  Y  A  T 
               
               
                   
               
               
                 cattacgccgagagcgtgaaaggtcgctttaccatcagccgtgatgacagvaaacgcagc 
               
               
                  H  Y  A  E  S  V  K  G  R  F  T  I  S  R  D  D  S  K  R  S 
               
               
                   
               
               
                 gtgtatctgcagatgaacacattacgtgctgaagacaccggtatctactattgcacccgc 
               
               
                  V  Y  L  Q  M  N  T  L  R  A  E  D  T  G  I  Y  Y  C  T  R 
               
               
                   
               
               
                 ggcaacggcaactatcgcgccatggattattggggccagggtaccagcgtgaccgttagt 
               
               
                  G  N  G  N  Y  R  A  M  D  Y  W  G  Q  G  T  S  V  T  V  S 
               
               
                   
               
               
                 agcggcggcggtggtagtggtggtggtggtagtggcggtggcggtagcgacattcaaatg 
               
               
                  S  G  G  G  G  S  G  G  G  G  S  G  G  G  G  S  D  I Q  M 
               
               
                   
               
               
                 acccagagtcctgcaagcctgagcgtgagcgtgggtgagaccgtgagcatcacatgccgc 
               
               
                  T  Q  S  P  A  S  L  S  V  S  V  G  E  T  V  S  I  T  C  R 
               
               
                   
               
               
                 gccagcgagaacatttatagcagcctggcctggtaccagcaaaaacagggtaaaagcccg 
               
               
                  A  S  E  N  I  Y  S  S  L  A  W  Y  Q  Q  K  Q  G  K  S  P 
               
               
                   
               
               
                 cagctgctggtgtatagcgccaccattctggcagatggtgtgccgagccgttttagtggc 
               
               
                  Q  L  L  V  Y  S  A  T  I  L  A  D  G  V  P  S  R  F  S  G 
               
               
                   
               
               
                 agtggcagtggtacccagtacagcctgaaaatcaacagcctgcagagcgaagacttcggc 
               
               
                  S  G  S  G  T  Q  Y  S  L  K  I  N  S  L  Q  S  E  D  F  G 
               
               
                   
               
               
                 acctactactgtcagcacttttggggcaccccgtatacctttggcggcggtaccaagctg 
               
               
                  T  Y  Y  C  Q  H  F  W  G  T  P  Y  T  F  G  G  G  T  K  L 
               
               
                   
               
               
                 gaaatcaaaggtggatccgcaggtagcgcaggcagtgcaggcagcggtggtagcgatatc 
               
               
                  E  I  K  G  G  S  A  G  S  A  G  S  A  G  S  G  G  S  D  I 
               
               
                   
               
               
                 cagatgacccaaagcccgagcagcttaagtgccagcgtgggcgatcgcgtgaccatcacc 
               
               
                  Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T  I  T 
               
               
                   
               
               
                 tgcaaagccagtcaggacgttaccacagccgtggcctggtatcagcagaaaccgggtaaa 
               
               
                  C  K  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P  G  K 
               
               
                   
               
               
                 gcccctaagctgctgatctattgggccagcacccgccacacaggtgttccgagtcgtttc 
               
               
                  A  P  K  L  L  I  Y  W  A  S  T  R  H  T  G  V  P  S  R  F 
               
               
                   
               
               
                 agcggcagcggtagcggtaccgattttaccctgaccatcagcagcctgcagccggaagac 
               
               
                  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P  E  D 
               
               
                   
               
               
                 ttcgcaacatactactgccagcagcactattctaccccgctgacattcggccagggcaca 
               
               
                  F  A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q  G  T 
               
               
                   
               
               
                 aaagtggagattaaa 
               
               
                  K  V  E  I  K 
               
               
                   
               
               
                 E10-2G4 LC N′ Fusion Sequence - Amino Acid (SEQ ID NO: 19): 
               
               
                 EVQLQESGGGLMQPGGSMKLSCVASGFTFSNYWMNWVRQSPEKGLEWVAEIRLK 
               
               
                   
               
               
                 SNNYATHYAESVKGRFTISRDDSKRSVYLQMNTLRAEDTGIYYCTRGNGNYRAMDYWGQGT 
               
               
                   
               
               
                 SVTVSS GGGGSGGGGSGGGGS DIQMTQSPASLSVSVGETVSITCRASENIYSSLRWYQQKQ 
               
               
                   
               
               
                 GKSPQLLVYSATILADGVPSRFSGSGSGTQYSLKINSLQSEDFGTYYCQHFWGTPYTFGGG 
               
               
                   
               
               
                 TKLEIK GGSAGSAGSAGSGGS DIQMTQSPSSLSASVGDRVTITCRASQDVTTAVAWYQQKP 
               
               
                   
               
               
                 GKAPKLLIYWASRLHNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQG 
               
               
                   
               
               
                 TKVEIK 
               
               
                   
               
               
                 Underlined region is glycine-rich linker polypeptide. Bold region 
               
               
                 is fusion linker polypeptide. 
               
               
                 Nucleotide (SEQ ID NO: 20): 
               
               
                 GAAGTTCAGCTGCAGGAAAGCGGCGGTGGTCTGATGCAGCCTGGTGGCAGCATG 
               
               
                   
               
               
                 AAACTGAGCTGTGTGGCCAGCGGTTTCACCTTCAGCAACTATTGGATGAACTGGGTGCGTC 
               
               
                   
               
               
                 AGAGTCCGGAAAAAGGCCTGGAATGGGTTGCCGAGATCCGCCTGAAGAGTAACAACTATGC 
               
               
                   
               
               
                 CACCCATTACGCCGAGAGCGTGAAAGGTCGCTTTACCATCAGCCGTGATGACAGCAAACGC 
               
               
                   
               
               
                 AGCGTGTATCTGCAGATGAACACATTACGTGCTGAAGACACCGGTATCTACTATTGCACCC 
               
               
                   
               
               
                 GCGGCAACGGCAACTATCGCGCCATGGATTATTGGGGCCAGGGTACCAGCGTGACCGTTAG 
               
               
                   
               
               
                 TAGCGGCGGCGGTGGTAGTGGTGGTGGTGGTAGTGGCGGTGGCGGTAGCGACATTCAAATG 
               
               
                   
               
               
                 ACCCAGAGTCCTGCAAGCCTGAGCGTGAGCGTGGGTGAGACCGTGAGCATCACATGCGGCG 
               
               
                   
               
               
                 CCAGCGAGAACATTTATAGCAGCCTGGCCTGGTACCAGCAAAAACAGGGTAAAAGCCCGCA 
               
               
                   
               
               
                 GGTGCTGGTGTATAGCGCCACCATTCTGGCAGATGGTGTGCCGAGCCGTTTTAGTGGCAGT 
               
               
                   
               
               
                 GGCAGTGGTACCCAGTACAGCCTGAAAATCAACAGCCTGCAGAGCGAAGACTTCGGCACCT 
               
               
                   
               
               
                 ACTACTGTCAGCACTTTTGGGGCACCCCGTATACCTTTGGCGGCGGTACCAAGCTGGAAAT 
               
               
                   
               
               
                 CAAAGGTGGATCCGCCGGTAGCGCAGGTAGTGCCGGTAGCGGTGGCAGCGATATCCAAATG 
               
               
                   
               
               
                 ACCCAGAGCCCGAGTAGCCTGAGTGCAAGTGTGGGCGATCGCGTTACCATCACCTGTCGCG 
               
               
                   
               
               
                 CAAGCCAGGACGTGACAACCGCCGTGGCCTGGTATCAGCAGAAACCTGGTAAAGCCCCGAA 
               
               
                   
               
               
                 GCTGCTGATTTACTGGGCCAGCCGCCTGCACAATGGTGTTCCGAGTCGCTTTAGCGGCAGT 
               
               
                   
               
               
                 GGCAGCGGCACAGACTTTACACTGACCATTAGCAGCCTGCAGCCGGAGGATTTTGCCACCT 
               
               
                   
               
               
                 ATTATTGCCAGCAGCATTACAGTACACCGCTGACCTTCGGCCAGGGTACCAAAGTGGAAAT 
               
               
                   
               
               
                 CAAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 19 and 20): 
               
               
                 gaagttcagctgcaggaaagcggcggtggtctgatgcagcctggtggcagcatgaaactg 
               
               
                  E  V  Q  L  Q  E  S  G  G  G  L  M  Q  P  G  G  S  M  K  L 
               
               
                   
               
               
                 agctgtgtggccagcggtttcaccttcagcaactattggatgaactgggtgcgtcagagt 
               
               
                  S  C  V  A  S  G  F  T  F  S  N  Y  W  M  N  W  V  R  Q  S 
               
               
                   
               
               
                 ccggaaaaaggcctggaatgggttgccgagatccgcctgaagagtaacaactatgccacc 
               
               
                  P  E  K  G  L  E  W  V  A  E  I  R  L  K  S  N  N  Y  A  T 
               
               
                   
               
               
                 cattacgccgagagcgtgaaaggtcgctttaccatcagccgtgatgacagcaaacgcagc 
               
               
                  H  Y  A  E  S  V  K  G  R  F  T  I  S  R  D  D  S  K  R  S 
               
               
                   
               
               
                 gtgtatctgcagatgaacacattacgtgctgaagacaccggtatctactattgcacccgc 
               
               
                  V  Y  L  Q  M  N  T  L  R  A  E  D  T  G  I  Y  Y  C  T  R 
               
               
                   
               
               
                 ggcaacggcaactatcgcgccatggattattggggccagggtaccagcgtgaccgttagt 
               
               
                  G  N  G  N  Y  R  A  M  D  Y  W  G  Q  G  T  S  V  T  V  S 
               
               
                   
               
               
                 agcggcggcggtggtagtggtggtggtggtagtggcggtggcggtagcgacattcaaatg 
               
               
                  S  G  G  G  G  S  G  G  G  G  S  G  G  G  G  S  D  I  Q  M 
               
               
                   
               
               
                 acccagagtcctgcaagcctgagcgtgagcgtgggtgagaccgtgagcatcacatgccgc 
               
               
                  T  Q  S  P  A  S  L  S  V  S  V  G  E  T  V  S  I  T  C  R 
               
               
                   
               
               
                 gccagcgagaacatttatagcagcctggcctggtaccagcaaaaacagggtaaaagcccg 
               
               
                  A  S  E  N  I  Y  S  S  L  A  W  Y  Q  Q  K  Q  G  K  S  P 
               
               
                   
               
               
                 cagctgctggtgtatagcgccaccattctggcagatggtgtgccgagccgttttagtggc 
               
               
                  Q  L  L  V  Y  S  A  T  I  L  A  D  G  V  P  S  R  F  S  G 
               
               
                   
               
               
                 agtggcagtggtacccagtacagcctgaaaatcaacagcctgcagagcgaagacttcggc 
               
               
                  S  G  S  G  T  Q  Y  S  L  K  I  N  S  L  Q  S  E  D  F  G 
               
               
                   
               
               
                 acctactactgtcagcacttttggggcaccccgtatacctttggcggcggtaccaagctg 
               
               
                  T  Y  Y  C  Q  H  F  W  G  T  P  Y  T  F  G  G  G  T  K  L 
               
               
                   
               
               
                 gaaatcaaaggtggatccgccggtagcgcaggtagtgccggtagcggtggcagcgatatc 
               
               
                  E  I  K  G  G  S  A  G  S  A  G  S  A  G  S  G  G  S  D  I 
               
               
                   
               
               
                 caaatgacccagagcccgagtagcctgagtgcaagtgtgggcgatcgcgttaccatcacc 
               
               
                  Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T  I  T 
               
               
                   
               
               
                 tgtcgcgcaagccaggacgtgacaaccgccgtggcctggtatcagcagaaacctggtaaa 
               
               
                  C  R  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P  G  K 
               
               
                   
               
               
                 gccccgaagctgctgatttactgggccagccgcctgcacaatggtgttccgagtcgcttt 
               
               
                  A  P  K  L  L  I  Y  W  A  S  R  L  H  N  G  V  P  S  R  F 
               
               
                   
               
               
                 agcggcagtggcagcggcacagactttacactgaccattagcagcctgcagccggaggat 
               
               
                  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P  E  D 
               
               
                   
               
               
                 tttgccacctattattgccagcagcattacagtacaccgctgaccttcggccagggtacc 
               
               
                  F  A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q  G  T 
               
               
                   
               
               
                 aaagtggaaatcaaa 
               
               
                  K  V  E  I  K 
               
               
                   
               
               
                 F4-4G7 LC N′ Fusion Sequence - Amino Acid (SEQ ID NO: 21): 
               
               
                   
               
               
                 EVQLQESGPELEMPGASVKISCKASGSSFTGFSMNWVKQSNGKSLEWIGNIDTY 
               
               
                   
               
               
                 YGGTTYNQKFKGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCARSAYYGSTFAYWGQGTLV 
               
               
                   
               
               
                 TVSA GGGGSGGGGSGGGGS DIQMTQSPASLSASVGETVTITCRASENIYSYLAWYQQKQGK 
               
               
                   
               
               
                 SPQLLVYNAKTLIEGVPSRFSGSGSGTQFSLKINSLQPEDFGSYFCQHHFGTPFTFGSGTE 
               
               
                   
               
               
                 LEIK GGSAGSAGSAGSGGS DIQMTQSPSSLSASVGDRVTITCRASQDVTTAVAWYQQKPGK 
               
               
                   
               
               
                 APKLLIYWASRLHNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQGTK 
               
               
                   
               
               
                 VEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide 
     
       
         
           
               
            
               
                 Nucleotide (SEQ ID NO: 22): 
               
               
                 GAGGTGCAGCTGCAAGAAAGTGGTCCGGAACTGGAAATGCCGGGTGCCAG 
               
               
                   
               
               
                 CGTGAAAATCAGCTGCAAAGCCAGCGGCAGTAGCTTTACCGGCTTTAGCA 
               
               
                   
               
               
                 TGAACTGGGTGAAACAGAGCAACGGCAAGAGCCTGGAGTGGATCGGCAAT 
               
               
                   
               
               
                 ATTGACACCTACTACGGCGGCACCACCTATAACCAGAAGTTCAAAGGCAA 
               
               
                   
               
               
                 AGCCACACTGACCGTGGACAAGAGTAGCAGTACAGCCTACATGCAGCTGA 
               
               
                   
               
               
                 AAAGCCTGACCAGCGAGGATAGCGCAGTGTATTACTGCGCACGCAGCGCC 
               
               
                   
               
               
                 TATTACGGCAGCACATTTGCCTACTGGGGTCAGGGTACCCTGGTGACAGT 
               
               
                   
               
               
                 TAGCGCAGGCGGTGGTGGCAGTGTGGTGGTGGTAGCGGTGGTGGTGGCAG 
               
               
                   
               
               
                 CGACATTCAAATGACACAGAGCCCGGCCAGTCTGAGTGCAAGCGTTGGCG 
               
               
                   
               
               
                 AAACCGTGACCATTACCTGCCGTGCCAGCGAGAACATCTATAGCTACCTG 
               
               
                   
               
               
                 GCCTGGTACCAGCAGAAGCAGGGTAAAAGCCCTCAGCTGCTGGTGTACAA 
               
               
                   
               
               
                 TGCCAAAACCCTGATCGAAGGCGTTCCGAGTCGCTTTAGTGGCAGCGGCA 
               
               
                   
               
               
                 GTGGCACCCAGTTCAGCCTGAAAATCAACAGCCTGCAACCGGAAGACTTT 
               
               
                   
               
               
                 GGCAGCTACTTCTGCCAGCACCATTTTGGCACACCGTTCACCTTCGGTAG 
               
               
                   
               
               
                 TGGCACCGAACTGGAGATTAAAGGTGGATCCGCAGGTAGCGCAGGCAGTG 
               
               
                   
               
               
                 CAGGCAGCGGTGGTAGCGATATCCAGATGACCCAAAGCCCGAGCAGCTTA 
               
               
                   
               
               
                 AGTGCCAGCGTGGGCGATCGCGTGACCATCACCTGCAAAGCCAGTCAGGA 
               
               
                   
               
               
                 CGTTACCACAGCCGTGGCCTGGTATCAGCAGAAACCGGGTAAAGCCCCTA 
               
               
                   
               
               
                 AGCTGCTGATCTATTGGGCCAGCACCCGCCACACAGGTGTTCCGAGTCGT 
               
               
                   
               
               
                 TTCAGCGGCAGCGGTAGCGGTACCGATTTTACCCTGACCATCAGCAGCCT 
               
               
                   
               
               
                 GCAGCCGGAAGACTTCGCAACATACTACTGCCAGCAGCACTATTCTACCC 
               
               
                   
               
               
                 CGCTGACATTCGGCCAGGGCACAAAAGTGGAGATTAAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 21 and 22): 
               
               
                 gaggtgcagctgcaagaaagtggtccggaactggaaatgccgggtgccag 
               
               
                 E  V  Q  L  Q  E  S  G  P  E  L  E  M  P  G  A  S 
               
               
                   
               
               
                 cgtgaaaatcagctgcaaagccagcggcagtagctttaccggctttagca 
               
               
                  V  K  I  S  C  K  A  S  G  S  S  F  T  G  F  S  M 
               
               
                   
               
               
                 tgaactgggtgaaacagagcaacggcaagagcctggagtggatcggcaat 
               
               
                   N  W  V  K  Q  S  N  G  K  S  L  E  W  I  G  N 
               
               
                   
               
               
                 attgacacctactacggcggcaccacctataaccagaagttcaaaggcaa 
               
               
                 I  D  T  Y  Y  G  G  T  T  Y  N  Q  K  F  K  G  K 
               
               
                   
               
               
                 agccacactgaccgtggacaagagtagcagtacagcctacatgcagctga 
               
               
                  A  T  L  T  V  D  K  S  S  S  T  A  Y  M  Q  L  K 
               
               
                   
               
               
                 aaagcctgaccagcgaggatagcgcagtgtattactgcgcacgcagcgcc 
               
               
                   S  L  T  S  E  D  S  A  V  Y  Y  C  A  R  S  A 
               
               
                   
               
               
                 tattacggcagcacatttgcctactggggtcagggtaccctggtgacagt 
               
               
                 Y  Y  G  S  T  F  A  Y  W  G  Q  G  T  L  V  T  V 
               
               
                   
               
               
                 tagcgcaggcggtggtggcagtggtggtggtggtagcggtggtggtggca 
               
               
                  S  A  G  G  G  G  S  G  G  G  G  S  G  G  G  G  S 
               
               
                   
               
               
                 gcgacattcaaatgacacagagcccggccagtctgagtgcaagcgttggc 
               
               
                   D  I  Q  M  T  Q  S  P  A  S  L  S  A  S  V  G 
               
               
                   
               
               
                 gaaaccgtgaccattacctgccgtgccagcgagaacatctatagctacct 
               
               
                 E  T  V  T  I  T  C  R  A  S  E  N  I  Y  S  Y  L 
               
               
                   
               
               
                 ggcctggtaccagcagaagcagggtaaaagccctcagctgctggtgtaca 
               
               
                  A  W  Y  W  W  K  Q  G  K  S  P  Q  L  L  V  Y  N 
               
               
                   
               
               
                 atgccaaaaccctgatcgaaggcgttccgagtcgctttagtggcagcggc 
               
               
                   A  K  T  L  I  E  G  V  P  S  R  F  S  G  S  G 
               
               
                   
               
               
                 agtggcacccagttcagcctgaaaatcaacagcctgcaaccggaagactt 
               
               
                 S  G  T  Q  F  S  L  K  I  N  S  L  Q  P  E  D  F 
               
               
                   
               
               
                 tggcagctacttctgccagcaccattttggcacaccgttcaccttcggta 
               
               
                  G  S  Y  F  C  Q  H  H  F  G  T  P  F  T  F  G  S 
               
               
                   
               
               
                 gtggcaccgaactggagattaaaggtggatccgcaggtagcgcaggcagt 
               
               
                   G  T  E  L  E  I  K  G  G  S  A  G  S  A  G  S 
               
               
                   
               
               
                 gcaggcagcggtggtagcgatatccagatgacccaaagcccgagcagctt 
               
               
                 A  G  S  G  G  S  D  I  Q  M  T  Q  S  P  S  S  L 
               
               
                   
               
               
                 aagtgccagcgtgggcgatcgcgtgaccatcacctgcaaagccagtcagg 
               
               
                  S  A  S  V  G  D  R  V  T  I  T  C  K  A  S  Q  D 
               
               
                   
               
               
                 acgttaccacagccgtggcctggtatcagcagaaaccgggtaaagcccct 
               
               
                   V  T  T  A  V  A  W  Y  Q  Q  K  P  G  K  A  P 
               
               
                   
               
               
                 aagctgctgatctattgggccagcacccgccacacaggtgttccgagtcg 
               
               
                 K  L  L  I  Y  W  A  S  T  R  H  T  G  V  P  S  F 
               
               
                   
               
               
                 tttcagcggcagcggtagcggtaccgattttaccctgaccatcagcagcc 
               
               
                  F  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L 
               
               
                   
               
               
                 tgcagccggaagacttcgcaacatactactgccagcagcactattctacc 
               
               
                   Q  P  E  D  F  A  T  Y  Y  C  Q  Q  H  Y  S  T 
               
               
                   
               
               
                 ccgctgacattcggccagggcacaaaagtggagattaaa 
               
               
                 P  L  T  F  G  Q  G  T  K  V  E  I  K 
               
               
                   
               
               
                 E10-4G7 LC N′ Fusion Sequence-Amino Acid 
               
               
                 (SEQ ID NO: 23): 
               
               
                 EVQLQESGPELEMPGASVKISCKASGSSFTGFSMNWVKQSNGKSLEWIGN 
               
               
                   
               
               
                 IDTYYGGTTYNQKFKGKATLTVDKSSSTAYMQLKSLTSEDSAVYYCARSA 
               
               
                   
               
               
                 YYGSTFAYWGQGTLTVSA GGGGSGGGGSGGGGS DIQMTQSPASLSASVGE 
               
               
                   
               
               
                 TVTITCRASENIYSYLAWYQQKQGKSPQLLVYNAKTLIEGVPSRFSGSGS 
               
               
                   
               
               
                 GTQFSLKINSLQPEDFGSYFCQHHFGTPFTFGSGTELEIK GGSAGSAGSA   
               
               
                   
               
               
                   GSGGS DIQMTQSPSSLSASVGDRVTITCRASQDVTTAVAWYQQKPGKAPK 
               
               
                   
               
               
                 LLIYWASRLHNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTP 
               
               
                   
               
               
                 LTFGQGTKVEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. 
     
       
         
           
               
            
               
                 Nucleotide (SEQ ID NO: 24): 
               
               
                 GAGGTGCAGCTGCAAGAAAGTGGTCCGGAACTGGAAATGCCGGGTGCCAG 
               
               
                   
               
               
                 CGTGAAAATCAGCTGCAAAGCCAGCGGCAGTAGCTTTACCGGCTTTAGCA 
               
               
                   
               
               
                 TGAACTGGGTGAAACAGAGCAACGGCAAGAGCCTGGAGTGGATCGGCAAT 
               
               
                   
               
               
                 ATTGACACCTACTACGGCGGCACCACCTATAACCAGAAGTTCAAAGGCAA 
               
               
                   
               
               
                 AGCCACACTGACCGTGGACAAGAGTAGCAGTACAGCCTACATGCAGCTGA 
               
               
                   
               
               
                 AAAGCCTGACCAGCGAGGATAGCGCAGTGTATTACTGCGCACGCAGCGCC 
               
               
                   
               
               
                 TATTACGGCAGCACATTTTGCCTACTGGGGTCAGGGTACCCTGGTGACAG 
               
               
                   
               
               
                 TTAGCGCAGGCGGTGGTGGCAGTGGTGGTGGTGGTAGCGGTGGTGGTGGC 
               
               
                   
               
               
                 AGCGACATTCAAATGACACAGAGCCCGGCCAGTCTGAGTGCAAGCGTTGG 
               
               
                   
               
               
                 CGAAACCGTGACCATTACCTGCCGTGCCAGCGAGAACATCTATAGCTACC 
               
               
                   
               
               
                 TGGCCTGGTACCAGCAGAAGCAGGGTAAAAGCCCTCAGCTGCTGGTGTAC 
               
               
                   
               
               
                 AATGCCAAAACCCTGATCGAAGGCGTTCCGAGTCGCTTTAGTGGCAGCGG 
               
               
                   
               
               
                 CAGTGGCACCCAGTTCAGCCTGAAAATCAACAGCCTGCAACCGGAAGACT 
               
               
                   
               
               
                 TTGGCAGCTACTTCTGCCAGCACCATTTTGGCACACCGTTCACCTTCGGT 
               
               
                   
               
               
                 AGTGGCACCGAACTGGAGATTAAAGGTGGATCCGCCGGTAGCGCAGGTAG 
               
               
                   
               
               
                 TGCCGGTAGCGGTGGCAGCGATATCCAAATGACCCAGAGCCCGAGTAGCC 
               
               
                   
               
               
                 TGAGTGCAAGTGTGGGCGATCGCGTTACCATCACCTGTCGCGCAAGCCAG 
               
               
                   
               
               
                 GACGTGACAACCGCCGTGGCCTGGTATCAGCAGAAACCTGGTAAAGCCCC 
               
               
                   
               
               
                 GAAGCTGCTGATTTACTGGGCCAGCCGCCTGCACAATGGTGTTCCGAGTC 
               
               
                   
               
               
                 GCTTTAGCGGCAGTGGCAGCGGCACAGACTTTACACTGACCATTAGCAGC 
               
               
                   
               
               
                 CTGCAGCCGGAGGATTTTGCCACCTATTATTGCCAGCAGCATTACAGTAC 
               
               
                   
               
               
                 ACCGCTGACCTTCGGCCAGGGTACCAAAGTGGAAATCAAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 23 and 24): 
               
               
                 gaggtgcagctgcaagaaagtggtccggaactggaaatgccgggtgccag 
               
               
                 E  V  Q  L  Q  E  S  G  P  E  L  E  M  P  G  A  S 
               
               
                   
               
               
                 cgtgaaaatcagctgcaaagccagcggcagtagctttaccggctttagca 
               
               
                  V  K  I  S  C  K  A  S  G  S  S  F  T  G  F  S  M 
               
               
                   
               
               
                 tgaactgggtgaaacagagcaacggcaagagcctggagtggatcggcaat 
               
               
                   N  W  V  K  Q  S  N  G  K  S  L  E  W  I  G  N 
               
               
                   
               
               
                 attgacacctactacggcggcaccacctataaccagaagttcaaaggcaa 
               
               
                 I  D  T  Y  Y  G  G  T  T  Y  N  Q  K  F  K  G  K 
               
               
                   
               
               
                 agccacactgaccgtggacaagagtagcagtacagcctacatgcagctga 
               
               
                  A  T  L  T  V  D  K  S  S  S  T  A  Y  M  Q  L  K 
               
               
                   
               
               
                 aaagcctgaccagcgaggatagcgcagtgtattactgcgcacgcagcgcc 
               
               
                   S  L  T  S  E  D  S  A  V  Y  Y  C  A  R  S  A 
               
               
                   
               
               
                 tattacggcagcacatttgcctactggggtcagggtaccctggtgacagt 
               
               
                 Y  Y  G  S  T  F  A  Y  W  G  Q  G  T  L  V  T  V 
               
               
                   
               
               
                 tagcgcaggcggtggtggcagtggtggtggtggtagcggtggtggtggca 
               
               
                  S  A  G  G  G  G  S  G  G  G  G  S  G  G  G  G  S 
               
               
                   
               
               
                 gcgacattcaaatgacacagagcccggccagtctgagtgcaagcgttggc 
               
               
                   D  I  Q  M  T  Q  S  P  A  S  L  S  A  S  V  G 
               
               
                   
               
               
                 gaaaccgtgaccattacctgccgtgccagcgagaacatctatagctacct 
               
               
                 E  T  V  T  I  T  C  R  A  S  E  N  I  Y  S  Y  L 
               
               
                   
               
               
                 ggcctggtaccagcagaagcagggtaaaagccctcagctgctggtgtaca 
               
               
                  A  W  Y  Q  Q  K  Q  G  K  S  P  Q  L  L  V  Y  N 
               
               
                   
               
               
                 atgccaaaaccctgatcgaaggcgttccgagtcgctttagtggcagcggc 
               
               
                   A  K  T  L  I  E  G  V  P  S  R  F  S  G  S  G 
               
               
                   
               
               
                 agtggcacccagttcagcctgaaaatcaacagcctgcaaccggaagactt 
               
               
                 S  G  T  Q  F  S  L  K  I  N  S  L  Q  P  E  D  F 
               
               
                   
               
               
                 tggcagctacttctgccagcaccattttggcacaccgttcaccttcggta 
               
               
                  G  S  Y  F  C  Q  H  H  F  G  T  P  F  T  F  G  S 
               
               
                   
               
               
                 gtggcaccgaactggagattaaaggtggatccgccggtagcgcaggtagt 
               
               
                   F  T  E  L  E  I  K  G  G  S  A  G  S  A  G  S 
               
               
                   
               
               
                 gccggtagcggtggcagcgatatccaaatgacccagagcccgagtagcct 
               
               
                 A  G  S  G  G  S  D  I  Q  M  T  Q  S  P  S  S  L 
               
               
                   
               
               
                 gagtgcaagtgtgggcgatcgcgttaccatcacctgtcgcgcaagccagg 
               
               
                  S  A  S  V  G  D  R  V  T  I  T  C  R  A  S  Q  D 
               
               
                   
               
               
                 acgtgacaaccgccgtggcctggtatcagcagaaacctggtaaagccccg 
               
               
                   V  T  T  A  V  A  W  Y  Q  Q  K  P  G  K  A  P 
               
               
                   
               
               
                 aagctgctgatttactgggccagccgcctgcacaatggtgttccgagtcg 
               
               
                 K  L  L  I  Y  W  A  S  R  L  H  N  G  V  P  S  R 
               
               
                   
               
               
                 ctttagcggcagtggcagcggcacagactttacactgaccattagcagcc 
               
               
                  F  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L 
               
               
                   
               
               
                 tgcagccggaggattttgccacctattattgccagcagcattacagtaca 
               
               
                   Q  P  E  D  F  A  T  Y  Y  C  Q  Q  H  Y  S  T 
               
               
                   
               
               
                 ccgctgaccttcggccagggtaccaaagtggaaatcaaa 
               
               
                 P  L  T  F  G  Q  G  T  K  V  E  I  K 
               
               
                   
               
               
                 F4-2G4 HC C′ Fusion Sequence-Amino Acid 
               
               
                 (SEQ ID NO: 25): 
               
               
                 EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY 
               
               
                   
               
               
                 IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL 
               
               
                   
               
               
                 YGNSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD 
               
               
                   
               
               
                 YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY 
               
               
                   
               
               
                 ICNVNHKPSNTKVDKKVEPKSCDKTHTCDKTHTCPPCPAPELLGRPSVFL 
               
               
                   
               
               
                 FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR 
               
               
                   
               
               
                 EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ 
               
               
                   
               
               
                 PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK 
               
               
                   
               
               
                 TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS 
               
               
                   
               
               
                 LSPGK   GGSAGSAGSAGSGGS   EVQLQESGGGLMQPGGSMKLSCVASGFTFS 
               
               
                   
               
               
                 NYWMNWVRQSPEKGLEWVAEIRLKSNNYATHYAESVKGRFTISRDDSKRS 
               
               
                   
               
               
                 VYLQMNTLRAEDTGIYYCTRGNGNYRAMDYWGQGTSVTVSS GGGGSGGGG   
               
               
                   
               
               
                   SGGGGS DIQMTQSPASLSVSVGETVSITRVRASENIYSSLAWYQQKQGKS 
               
               
                   
               
               
                 PQLLVYSATILADGVPSRFSGSGSTQYSLKINSLQSEDFGTYYCQHFWGT 
               
               
                   
               
               
                 PYTFGGGTKLEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. 
     
       
         
           
               
            
               
                 Nucleotide (SEQ ID NO: 26): 
               
               
                 GAAGTTCAACTGGTTGAGAGTGGCGGTGGCTTAGTTCAACCGGGCGGTAG 
               
               
                   
               
               
                 TTTACGCCTGAGTTGTGCAGCCAGCGGTTTCGCCTTCAACTATTATGACA 
               
               
                   
               
               
                 TGTTTTGGGTGCGCCAGGCACCGGGTAAAGGCCTGGAGTGGGTGGCCTAT 
               
               
                   
               
               
                 ATCAAACCGGGCGGTGGCAACACCTATTACGCCGATAGCGTGAAAGGTCG 
               
               
                   
               
               
                 CTTTACCATCAGCGCAGATACCAGCAAGAATACCGCCTACCTGCAGATGA 
               
               
                   
               
               
                 ATAGCCTGCGTGCCGAAGACACCGCCGTTTATTATTGCGCCCGCCAGCTG 
               
               
                   
               
               
                 TACGGCAATAGCTTTTTCGATTACTGGGGCCAGGGCACCCTGGTTACCGT 
               
               
                   
               
               
                 TAGCAGCGCTAGCACCAAGGGTCCGAGCGTGTTTCCTCTGGCACCTAGCA 
               
               
                   
               
               
                 GTAAAAGCACCAGTGGTGGTACAGCAGCCCTGGGTTGCCTGGTGAAGGAT 
               
               
                   
               
               
                 TACTTTCCGGAGCCGGTGACCGTTAGTTGGAATAGCGGCGCCCTGACCAG 
               
               
                   
               
               
                 TGGCGTTCATACATTTCCGGCCGTGCTGCAGAGTAGTGGCCTGTACAGCC 
               
               
                   
               
               
                 TGAGTAGCGTTGTTACCGTTCCGAGCAGCAGCCTGGGCACCCAGACCTAT 
               
               
                   
               
               
                 ATTTGCAATGTTAACCATAAACCGAGCAACACAAAAGTTGATAAAAAAGT 
               
               
                   
               
               
                 TGAACCGAAGAGCTGTGACAAAACCCATACATGTGACAAAACACACACCT 
               
               
                   
               
               
                 GCCCGCCTTGTCCGGCACCTGAGCTGCTGGGTCGCCCGAGCGTTTTTCTG 
               
               
                   
               
               
                 TTTCCTCCGAAACCGAAAGACACCCTGATGATCAGCCGCACACCTGAGGT 
               
               
                   
               
               
                 GACCTGTGTTGTGGTGGATGTGAGCCACGAAGATCCTGAAGTTAAGTTTA 
               
               
                   
               
               
                 ACTGGTATGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGT 
               
               
                   
               
               
                 GAAGAGCAGTACAACAGCACCTATCGTGTTGTTAGTGTGCTGACCGTTCT 
               
               
                   
               
               
                 GCACCAAGATTGGCTGAACGGCAAGGAGTATAAATGCAAGGTTAGCAATA 
               
               
                   
               
               
                 AAGCCCTGCCGGCCCCGATCGAGAAGACCATCAGCAAAGCCAAAGGTCAG 
               
               
                   
               
               
                 CCGCGTGAGCCTCAGGTGTATACACTGCCGCCTAGCCGTGAGGAGATGAC 
               
               
                   
               
               
                 CAAGAATCAGGTTAGCCTGACCTGTCTGGTGAAAGGCTTTTACCCGAGCG 
               
               
                   
               
               
                 ATATCGCCGTTGAGTGGGAAAGCAATGGTCAGCCTGAGAACAACTACAAG 
               
               
                   
               
               
                 ACCACCCCGCCTGTTTTAGACAGTGATGGTAGCTTTTTCTTATACAGCAA 
               
               
                   
               
               
                 ACTGACCGTTGATAAGAGCCGCTGGCAGCAGGGCAATGTGTTTAGCTGCA 
               
               
                   
               
               
                 GTGTTATGCATGAGGCCCTGCATAACCACTATACCCAGAAGAGTCTGAGC 
               
               
                   
               
               
                 CTGAGTCCTGGCAAAGGTGGATCCGCAGGCAGTGCAGGTAGTGCCGGCAG 
               
               
                   
               
               
                 CGGTGGTAGTGAGGTTCAGCTGCAGGAAAGCGGCGGCGGCTTAATGCAGC 
               
               
                   
               
               
                 CTGGCGGTAGCATGAAGCTGAGCTGCGTGGCCAGCGGCTTCACCTTTAGC 
               
               
                   
               
               
                 AATTACTGGATGAACTGGGTGCGCCAGAGCCCGGAAAAAGGCCTGGAATG 
               
               
                   
               
               
                 GGTGGCAGAGATCCGTCTGAAGAGCAACAACTACGCCACCCACTATGCCG 
               
               
                   
               
               
                 AAAGCGTGAAGGGTCGCTTTACCATCAGCCGCGATGACAGCAAACGCAGC 
               
               
                   
               
               
                 GTGTATCTGCAGATGAACACCCTGCGTGCAGAGGACACCGGCATCTATTA 
               
               
                   
               
               
                 TTGCACCCGCGGCAACGGTAATTATCGCGCCATGGACTACTGGGGTCAGG 
               
               
                   
               
               
                 GTACCAGCGTGACCGTTAGCAGTGGCGGTGGTGGTAGCGGTGGTGGTGGT 
               
               
                   
               
               
                 AGCGGTGGTGGTGGCAGCGATATTCAAATGACCCAGAGCCCTGCCAGCCT 
               
               
                   
               
               
                 GAGCGTGAGTGTTGGCGAAACCGTGAGCATCACCTGCCGCGCCAGCGAGA 
               
               
                   
               
               
                 ACATCTATAGTAGCCTGGCCTGGTACCAGCAGAAACAGGGCAAAAGCCCG 
               
               
                   
               
               
                 CAGCTGCTGGTGTATAGCGCAACCATTCTGGCAGATGGCGTTCCGAGCCG 
               
               
                   
               
               
                 TTTTAGCGGTAGCGGCAGCGGCACACAGTACAGCCTGAAGATCAACAGCC 
               
               
                   
               
               
                 TGCAGAGCGAGGACTTTGGCACCTATTACTGCCAGCACTTTTGGGGTACC 
               
               
                   
               
               
                 CCGTATACCTTCGGCGGCGGCACCAAACTGGAAATTAAATAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 25 and 26): 
               
               
                 gaagttcaactggttgagagtggcggtggcttagttcaaccgggcggtag 
               
               
                 E  V  Q  L  V  E  S  G  G  G  L  V  Q  P  G  G  S 
               
               
                   
               
               
                 tttacgcctgagttgtgcagccagcggtttcgccttcaactattatgaca 
               
               
                  L  R  L  S  C  A  A  S  G  F  A  F  N  Y  Y  D  M 
               
               
                   
               
               
                 tgttttgggtgcgccaggcaccgggtaaaggcctggagtgggtggcctat 
               
               
                   F  W  V  R  Q  A  P  G  K  G  L  E  W  V  A  Y 
               
               
                   
               
               
                 atcaaaccgggcggtggcaacacctattacgccgatagcgtgaaaggtcg 
               
               
                 I  K  P  G  G  G  N  T  Y  Y  A  D  S  V  K  G  R 
               
               
                   
               
               
                 ctttaccatcagcgcagataccagcaagaataccgcctacctgcagatga 
               
               
                  F  T  I  S  A  S  T  K  S  N  T  A  Y  L  Q  M  N 
               
               
                   
               
               
                 atagcctgcgtgccgaagacaccgccgtttattattgcgcccgccagctg 
               
               
                   S  L  R  A  E  D  T  A  V  Y  Y  C  A  R  Q  L 
               
               
                   
               
               
                 tacggcaatagctttttcgattactggggccagggcaccctggttaccgt 
               
               
                 Y  G  N  S  F  F  D  Y  W  G  Q  G  T  L  V  T  V 
               
               
                   
               
               
                 tagcagcgctagcaccaagggtccgagcgtgtttcctctggcacctagca 
               
               
                  S  S  A  S  T  K  G  P  S  V  F  P  L  A  P  S  S 
               
               
                   
               
               
                 gtaaaagcaccagtggtggtacagcagccctgggttgcctggtgaaggat 
               
               
                   K  S  T  S  G  G  T  A  A  L  G  C  L  V  K  D 
               
               
                   
               
               
                 tactttccggagccggtgaccgttagttggaatagcggcgccctgaccag 
               
               
                 Y  F  P  E  P  V  T  V  S  W  N  S  G  A  L  T  S 
               
               
                   
               
               
                 tggcgttcatacatttccggccgtgctgcagagtagtggcctgtacagcc 
               
               
                  G  V  H  T  F  P  A  V  L  Q  S  S  G  L  Y  S  L 
               
               
                   
               
               
                 tgagtagcgttgttaccgttccgagcagcagcctgggcacccagacctat 
               
               
                   S  S  V  V  T  V  P  S  S  S  L  G  T  Q  T  Y 
               
               
                   
               
               
                 atttgcaatgttaaccataaaccgagcaacacaaaagttgataaaaaagt 
               
               
                 I  C  N  V  N  H  K  P  S  N  T  K  V  D  K  K  V 
               
               
                   
               
               
                 tgaaccgaagagctgtgacaaaacccatacatgtgacaaaacacacacct 
               
               
                  E  P  K  S  C  D  K  T  H  T  C  D  K  T  H  T  C 
               
               
                   
               
               
                 gcccgccttgtccggcacctgagctgctgggtcgcccgagcgtttttctg 
               
               
                   P  P  C  P  A  P  E  L  L  G  R  P  S  V  F  L 
               
               
                   
               
               
                 tttcctccgaaaccgaaagacaccctgatgatcagccgcacacctgaggt 
               
               
                 F  P  P  K  P  K  D  T  L  M  I  S  R  T  P  E  V 
               
               
                   
               
               
                 gacctgtgttgtggtggatgtgagccacgaagatcctgaagttaagttta 
               
               
                  T  C  V  V  V  D  V  S  H  E  D  P  E  V  K  F  N 
               
               
                   
               
               
                 actggtatgtggatggcgtggaggtgcataatgccaagacaaagccgcgt 
               
               
                   W  Y  V  D  G  V  E  V  H  N  A  K  T  K  P  R 
               
               
                   
               
               
                 gaagagcagtacaacagcacctatcgtgttgttagtgtgctgaccgttct 
               
               
                 E  E  Q  Y  N  S  T  Y  R  V  V  S  V  L  T  V  L 
               
               
                   
               
               
                 gcaccaagattggctgaacggcaaggagtataaatgcaaggttagcaata 
               
               
                  H  Q  D  W  L  N  G  K  E  Y  K  C  K  V  S  N  K 
               
               
                   
               
               
                 aagccctgccggccccgatcgagaagaccatcagcaaagccaaaggtcag 
               
               
                   A  L  P  A  P  I  E  K  T  I  S  K  A  K  G  Q  
               
               
                   
               
               
                 ccgcgtgagcctcaggtgtatacactgccgcctagccgtgaggagatgac 
               
               
                 P  R  E  P  Q  V  Y  T  L  P  P  S  R  E  E  M  T 
               
               
                   
               
               
                 caagaatcaggttagcctgacctgtctggtgaaaggcttttacccgagcg 
               
               
                  K  N  Q  V  S  L  T  C  L  V  K  G  F  Y  P  S  D 
               
               
                   
               
               
                 atatcgccgttgagtgggaaagcaatggtcagcctgagaacaactacaag 
               
               
                   I  A  V  E  W  E  S  N  G  Q  P  E  N  N  Y  K 
               
               
                   
               
               
                 accaccccgcctgttttagacagtgatggtagctttttcttatacagcaa 
               
               
                 T  T  P  P  V  L  D  S  D  G  S  F  F  L  Y  S  K 
               
               
                   
               
               
                 actgaccgttgataagagccgctggcagcagggcaatgtgtttagctgca 
               
               
                  L  T  V  D  K  S  R  W  Q  Q  G  N  V  F  S  C  S 
               
               
                   
               
               
                 gtgttatgcatgaggccctgcataaccactatacccagaagagtctgagc 
               
               
                   V  M  H  E  A  L  H  N  H  Y  T  Q  K  S  L  S 
               
               
                   
               
               
                 ctgagtcctggcaaaggtggatccgcaggcagtgcaggtagtgccggcag 
               
               
                 L  S  P  G  K  G  G  S  A  G  S  A  G  S  A  G  S 
               
               
                   
               
               
                 cggtggtagtgaggttcagctgcaggaaagcggcggcggcttaatgcagc 
               
               
                  G  G  S  E  V  Q  L  Q  E  S  G  G  G  L  M  Q  P 
               
               
                   
               
               
                 ctggcggtagcatgaagctgagctgcgtggccagcggcttcacctttagc 
               
               
                   G  G  S  M  K  L  S  C  V  A  S  G  F  T  F  S 
               
               
                   
               
               
                 aattactggatgaactgggtgcgccagagcccggaaaaaggcctggaatg 
               
               
                 N  Y  W  M  N  W  V  R  Q  S  P  E  K  G  L  E  W 
               
               
                   
               
               
                 ggtggcagagatccgtctgaagagcaacaactacgccacccactatgccg 
               
               
                  V  A  E  I  R  L  K  S  N  N  Y  A  T  H  Y  A  E 
               
               
                   
               
               
                 aaagcgtgaagggtcgctttaccatcagccgcgatgacagcaaacgcagc 
               
               
                   S  V  K  G  R  F  T  I  S  R  D  D  S  K  R  S 
               
               
                   
               
               
                 gtgtatctgcagatgaacaccctgcgtgcagaggacaccggcatctatta 
               
               
                 V  Y  L  Q  M  N  T  L  R  A  E  D  T  G  I  Y  Y 
               
               
                   
               
               
                 ttgcacccgcggcaacggtaattatcgcgccatggactactggggtcagg 
               
               
                  C  T  R  G  N  G  N  Y  R  A  M  D  Y  W  G  Q  G 
               
               
                   
               
               
                 gtaccagcgtgaccgttagcagtggcggtggtggtagcggtggtggtggt 
               
               
                   T  S  V  T  V  S  S  G  G  G  G  S  G  G  G  G 
               
               
                   
               
               
                 agcggtggtggtggcagcgatattcaaatgacccagagccctgccagcct 
               
               
                 S  G  G  G  G  S  D  I  Q  M  T  Q  S  P  A  S  L 
               
               
                   
               
               
                 gagcgtgagtgttggcgaaaccgtgagcatcacctgccgcgccagcgaga 
               
               
                  S  V  S  V  G  E  T  V  S  I  T  C  R  A  S  E  N 
               
               
                   
               
               
                 acatctatagtagcctggcctggtaccagcagaaacagggcaaaagcccg 
               
               
                   I  Y  S  S  L  A  W  Y  Q  Q  K  Q  G  K  S  P 
               
               
                   
               
               
                 cagctgctggtgtatagcgcaaccattctggcagatggcgttccgagccg 
               
               
                 Q  L  L  V  Y  S  A  T  I  L  A  D  G  V  P  S  R 
               
               
                   
               
               
                 ttttagcggtagcggcagcggcacacagtacagcctgaagatcaacagcc 
               
               
                  F  S  G  S  G  S  G  T  Q  Y  S  L  K  I  N  S  L 
               
               
                   
               
               
                 tgcagagcgaggactttggcacctattactgccagcacttttggggtacc 
               
               
                   Q  S  E  D  F  G  T  Y  Y  C  Q  H  F  W  G  T 
               
               
                   
               
               
                 ccgtataccttcggcggcggcaccaaactggaaattaaataa 
               
               
                 P  Y  T  F  G  G  G  T  K  L  E  I  K  - 
               
               
                   
               
               
                 F4-2G4 LC C′ Fusion Sequence-Amino Acid 
               
               
                 (SEQ ID NO: 27): 
               
               
                 DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW 
               
               
                   
               
               
                 ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ 
               
               
                   
               
               
                 GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV 
               
               
                   
               
               
                 DNALQSGNSQESVTEQDSKDSTYSLSSTLTSKADYEKHKVYACEVTHQGL 
               
               
                   
               
               
                 SSPVTKSFNRGECGGS   GGSAGSAGSAGSGGS   EVQLQESGGGLMQPGGSMK 
               
               
                   
               
               
                 LSCVASGFTFSNYWMNWVRQSPEKGLEWVAEIRLKSNNYATHYAESVKGR 
               
               
                   
               
               
                 RFTISRDDSKRSVYLQMNTLRAEDTGIYYCTRGNGNYRAMDYWGQGTSVT 
               
               
                   
               
               
                 VSS GGGGSGGGGSGGGGS DIQMTQSPASLSVSVGETVSITVRASENIYSS 
               
               
                   
               
               
                 LAWYQQKQGKSPQLLVYSATILADGVPSRFSGSGSGTQYSLKINSLQSED 
               
               
                   
               
               
                 FGTYYCQHFWGTPYTFGGGTKLEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide 
     
       
         
           
               
            
               
                 Nucleotide (SEQ ID NO: 28): 
               
               
                 GACATTCAGATGACCCAAAGTCCGAGCAGCCTGAGTGCCAGTGTTGGTGA 
               
               
                   
               
               
                 TCGCGTGACAATCACATGCAAGGCCAGTCAGGACGTGACCACCGCAGTGG 
               
               
                   
               
               
                 CCTGGTATCAGCAGAAACCGGGTAAGGCCCCGAAGCTGCTGATCTATTGG 
               
               
                   
               
               
                 GCCAGTACCCGCCACACCGGTGTTCCTAGTCGCTTCAGTGGCAGTGGCAG 
               
               
                   
               
               
                 CGGCACAGATTTCACCCTGACCATCAGCAGCCTGCAACCGGAAGATTTTG 
               
               
                   
               
               
                 CCACCTACTACTGCCAGCAGCACTATAGCACCCCGCTGACCTTTGGCCAG 
               
               
                   
               
               
                 GGCACCAAGGTTGAGATTAAACGTACGGTGGCAGCACCGAGCGTGTTTAT 
               
               
                   
               
               
                 CTTTCCGCCGAGCGACGAACAACTGAAAAGTGGCACAGCCAGCGTGGTGT 
               
               
                   
               
               
                 GTTTACTGAACAACTTCTATCCTCGCGAGGCCAAGGTGCAGTGGAAAGTG 
               
               
                   
               
               
                 GACAATGCACTGCAGAGTGGCAATAGCCAGGAGAGCGTGACCGAACAGGA 
               
               
                   
               
               
                 TAGCAAAGATAGCACCTATAGCCTGAGTAGCACCCTGACCCTGAGCAAGG 
               
               
                   
               
               
                 CCGATTATGAGAAGCACAAGGTGTATGCATGCGAGGTTACCCATCAGGGC 
               
               
                   
               
               
                 CTGAGCAGCCCGGTGACCAAAAGCTTTAACCGTGGCGAATGCGGTGGTAG 
               
               
                   
               
               
                 TGGTGGATCCGCAGGCAGTGCAGGTAGTGCCGGCAGCGGTGGTAGTGAGG 
               
               
                   
               
               
                 TTCAGCTGCAGGAAAGCGGCGGCGGCTTAATGCAGCCTGGCGGTAGCATG 
               
               
                   
               
               
                 AAGCTGAGCTGCGTGGCCAGCGGCTTCACCTTTAGCAATTACTGGATGAA 
               
               
                   
               
               
                 CTGGGTGCGCCAGAGCCCGGAAAAAGGCCTGGAATGGGTGGCAGAGATCC 
               
               
                   
               
               
                 GTCTGAAGAGCAACAACTACGCCACCCACTATGCCGAAAGCGTGAAGGGT 
               
               
                   
               
               
                 CGCTTTACCATCAGCCGCGATGACAGCAAACGCAGCGTGTATCTGCAGAT 
               
               
                   
               
               
                 GAACACCCTGCGTGCAGAGCATCAGCCGCGATGACAGCAAACGCAGCGTG 
               
               
                   
               
               
                 TATCTGCAGATGAACACCCTGCGTGCAGAGGTCAGGGTACCAGCGTGACC 
               
               
                   
               
               
                 GTTAGCAGTGGCGGTGGTGGTAGCGGTGGTGGTGGTAGCGGTGGTGGTGG 
               
               
                   
               
               
                 CAGCGATATTCAAATGACCCAGAGCCCTGCCAGCCTGAGCGTGAGTGTTG 
               
               
                   
               
               
                 GCGAAACCGTGAGCATCACCTGCCGCGCCAGCGAGAACATCTATAGTAGC 
               
               
                   
               
               
                 CTGGCCTGGTACCAGCAGAAACAGGGCAAAAGCCCGCAGCTGCTGGTGTA 
               
               
                   
               
               
                 TAGCGCAACCATTCTGGCAGATGGCGTTCCGAGCCGTTTTAGCGGTAGCG 
               
               
                   
               
               
                 GCAGCGGCACACAGTACAGCCTGAAGATCAACAGCCTGCAGAGCGAGGAC 
               
               
                   
               
               
                 TTTGGCACCTATTACTGCCAGCACTTTTGGGGTACCCCGTATACCTTCGG 
               
               
                   
               
               
                 CGGCGGCACCAAACTGGAAATTAAATA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 27 and 28): 
               
               
                 gacattcagatgacccaaagtccgagcagcctgagtgccagtgttggtga 
               
               
                 D  I  Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D 
               
               
                   
               
               
                 tcgcgtgacaatcacatgcaaggccagtcaggacgtgaccaccgcagtgg 
               
               
                  R  V  T  I  T  C  K  A  S  Q  D  V  T  T  A  V  A 
               
               
                   
               
               
                 cctggtatcagcagaaaccgggtaaggccccgaagctgctgatctattgg 
               
               
                   W  Y  Q  Q  K  P  G  K  A  P  K  L  L  I  Y  W   
               
               
                   
               
               
                 gccagtacccgccacaccggtgttcctagtcgcttcagtggcagtggcag 
               
               
                 A  S  T  R  H  T  G  V  P  S  R  F  S  G  S  G  S 
               
               
                   
               
               
                 cggcacagatttcaccctgaccatcagcagcctgcaaccggaagattttg 
               
               
                  G  T  D  F  T  L  T  I  S  S  L  Q  P  E  D  F  A 
               
               
                   
               
               
                 ccacctactactgccagcagcactatagcaccccgctgacctttggccag 
               
               
                   T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q 
               
               
                   
               
               
                 ggcaccaaggttgagattaaacgtacggtggcagcaccgagcgtgtttat 
               
               
                 G  T  K  V  E  I  K  R  T  V  A  A  P  S  V  F  I 
               
               
                   
               
               
                 ctttccgccgagcgacgaacaactgaaaagtggcacagccagcgtggtgt 
               
               
                  F  P  P  S  D  E  Q  L  K  S  G  T  A  S  V  V  C 
               
               
                   
               
               
                 gtttactgaacaacttctatcctcgcgaggccaaggtgcagtggaaagtg 
               
               
                   L  L  N  N  F  Y  P  R  E  A  K  V  Q  W  K  V 
               
               
                   
               
               
                 gacaatgcactgcagagtggcaatagccaggagagcgtgaccgaacagga 
               
               
                 D  N  A  L  Q  S  G  N  S  Q  E  S  V  T  E  Q  D 
               
               
                   
               
               
                 tagcaaagatagcacctatagcctgagtagcaccctgaccctgagcaagg 
               
               
                  S  K  D  S  T  Y  S  L  S  S  T  L  T  L  S  K  A 
               
               
                   
               
               
                 ccgattatgagaagcacaaggtgtatgcatgcgaggttacccatcagggc 
               
               
                   D  Y  E  K  H  K  V  Y  A  C  E  V  T  H  Q  G 
               
               
                   
               
               
                 ctgagcagcccggtgaccaaaagctttaaccgtggcgaatgcggtggtag 
               
               
                 L  S  S  P  V  T  K  S  F  N  R  G  E  C  G  G  S 
               
               
                   
               
               
                 tggtggatccgcaggcagtgcaggtagtgccggcagcggtggtagtgagg 
               
               
                  G  G  S  A  G  S  A  G  S  A  G  S  G  G  S  E  V 
               
               
                   
               
               
                 ttcagctgcaggaaagcggcggcggcttaatgcagcctggcggtagcatg 
               
               
                   Q  L  Q  E  S  G  G  G  L  M  Q  P  G  G  S  M 
               
               
                   
               
               
                 aagctgagctgcgtggccagcggcttcacctttagcaattactggatgaa 
               
               
                 K  L  S  C  V  A  S  G  F  T  F  S  N  Y  W  M  N 
               
               
                   
               
               
                 ctgggtgcgccagagcccggaaaaaggcctggaatgggtggcagagatcc 
               
               
                  W  V  R  Q  S  P  E  K  G  L  E  W  V  A  E  I  R 
               
               
                   
               
               
                 gtctgaagagcaacaactacgccacccactatgccgaaagcgtgaagggt 
               
               
                   L  K  S  N  N  Y  A  T  H  Y  A  E  S  V  K  G 
               
               
                   
               
               
                 cgctttaccatcagccgcgatgacagcaaacgcagcgtgtatctgcagat 
               
               
                 R  F  T  I  S  R  D  D  S  K  R  S  V  Y  L  Q  M 
               
               
                   
               
               
                 gaacaccctgcgtgcagaggacaccggcatctattattgcacccgcggca 
               
               
                  N  T  L  R  A  E  D  T  G  I  Y  Y  C  T  R  G  N 
               
               
                   
               
               
                 acggtaattatcgcgccatggactactggggtcagggtaccagcgtgacc 
               
               
                   G  N  Y  R  A  M  D  Y  W  G  Q  G  T  S  V  T 
               
               
                   
               
               
                 gttagcagtggcggtggtggtagcggtggtggtggtagcggtggtggtgg 
               
               
                 V  S  S  G  G  G  G  S  G  G  G  G  S  G  G  G  G 
               
               
                   
               
               
                 cagcgatattcaaatgacccagagccctgccagcctgagcgtgagtgttg 
               
               
                  S  D  I  Q  M  T  Q  S  P  A  S  L  S  V  S  V  G 
               
               
                   
               
               
                 gcgaaaccgtgagcatcacctgccgcgccagcgagaacatctatagtagc 
               
               
                   E  T  V  S  I  T  C  R  A  S  E  N  I  Y  S  S 
               
               
                   
               
               
                 ctggcctggtaccagcagaaacagggcaaaagcccgcagctgctggtgta 
               
               
                 L  A  W  Y  Q  Q  K  Q  G  K  S  P  Q  L  L  V  Y 
               
               
                   
               
               
                 tagcgcaaccattctggcagatggcgttccgagccgttttagcggtagcg 
               
               
                  S  A  T  I  L  A  D  G  V  P  S  R  F  S  G  S  G 
               
               
                   
               
               
                 gcagcggcacacagtacagcctgaagatcaacagcctgcagagcgaggac 
               
               
                   S  G  T  Q  Y  S  L  K  I  N  S  L  Q  S  E  D 
               
               
                   
               
               
                 tttggcacctattactgccagcacttttggggtaccccgtataccttcgg 
               
               
                 F  G  T  Y  Y  C  Q  H  F  W  G  T  P  Y  T  F  G 
               
               
                   
               
               
                 cggcggcaccaaactggaaattaaataa 
               
               
                  G  G  T  K  L  E  I  K  - 
               
               
                   
               
               
                 E10-2G4 LC C′ Fusion Sequence-Amino Acid 
               
               
                 (SEQ ID NO: 29): 
               
               
                 DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW 
               
               
                   
               
               
                 ASRLHNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ 
               
               
                   
               
               
                 GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV 
               
               
                   
               
               
                 DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG 
               
               
                   
               
               
                 LSSPVTKSFNRGECGGS   GGSAGSAGSAGS   GGSEVQLQESGGGLMQPGGSM 
               
               
                   
               
               
                 KLSCVASGFTFSNYWMNWVRQSPEKGLEWVAEIRLKSNNYATHYAESVKG 
               
               
                   
               
               
                 RFTISRDDSKRSVYLQMNTLRAEDTGIYYCTRGNGNYRAMDYWGQGTSVT 
               
               
                   
               
               
                 VSS GGGGSGGGGSGGGGS DIQMTQSPASLSVSVGETVSITCRASENIYSS 
               
               
                   
               
               
                 LAWYQQKQGKSPQLLVYSATILADGVPSRFSGSGSGTQYSLKINSLQSED 
               
               
                   
               
               
                 FGTYYCQHFWGTPYTFGGGTKLEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. 
     
       
         
           
               
            
               
                 Nucleotide (SEQ ID NO: 30): 
               
               
                 GATATCCAGATGACCCAGTCCCCGAGCTCCCTGTCCGCCTCTGTGGGCGA 
               
               
                   
               
               
                 TAGGGTCACCATCACCTGCCGGGCGAGCCAGGATGTGACCACCGCTGTAG 
               
               
                   
               
               
                 CCTGGTATCAACAGAAACCAGGAAAAGCTCCGAAGCTTCTGATTTACTGG 
               
               
                   
               
               
                 GCGAGCCGTCTTCATAATGGCGTGCCGAGCCGCTTTAGCGGCAGCGGCTC 
               
               
                   
               
               
                 CGGGACGGATTTCACTCTGACCATCAGCAGTCTGCAGCCGGAAGACTTCG 
               
               
                   
               
               
                 CAACTTATTACTGTCAGCAACATTATAGCACCCCGCTGACGTTCGGACAG 
               
               
                   
               
               
                 GGTACCAAGGTGGAGATCAAACGTACGGTGGCAGCACCGAGCGTGTTTAT 
               
               
                   
               
               
                 CTTTCCGCCGAGCGACGAACAACTGAAAAGTGGCACAGCCAGCGTGGTGT 
               
               
                   
               
               
                 GTTTACTGAACAACTTCTATCCTCGCGAGGCCAAGGTGCAGTGGAAAGTG 
               
               
                   
               
               
                 GACAATGCACTGCAGAGTGGCAATAGCCAGGAGAGCGTGACCGAACAGGA 
               
               
                   
               
               
                 TAGCAAAGATAGCACCTATAGCCTGAGTAGCACCCTGACCCTGAGCAAGG 
               
               
                   
               
               
                 CCGATTATGAGAAGCACAAGGTGTATGCATGCGAGGTTACCCATCAGGGC 
               
               
                   
               
               
                 CTGAGCAGCCCGGTGACCAAAAGCTTTAACCGTGGCGAATGCGGTGGTAG 
               
               
                   
               
               
                 TGGTGGATCCGCAGGCAGTGCAGGTAGTGCCGGCAGCGGTGGTAGTGAGG 
               
               
                   
               
               
                 TTCAGCTGCAGGAAAGCGGCGGCGGCTTAATGCAGCCTGGCGGTAGCATG 
               
               
                   
               
               
                 AAGCTGAGCTGCGTGGCCAGCGGCTTCACCTTTAGCAATTACTGGATGAA 
               
               
                   
               
               
                 CTGGGTGCGCCAGAGCCCGGAAAAAGGCCTGGAATGGGTGGCAGAGATCC 
               
               
                   
               
               
                 GTCTGAAGAGCAACAACTACGCCACCCACTATGCCGAAAGCGTGAAGGGT 
               
               
                   
               
               
                 CGCTTTACCATCAGCCGCGATGACAGCAAACGCAGCGTGTATCTGCAGAT 
               
               
                   
               
               
                 GAACACCCTGCGTGCAGAGGACACCGGCATCTATTATTGCACCCGCGGCA 
               
               
                   
               
               
                 ACGGTAATTATCGCGCCATGGACTACTGGGGTCAGGGTACCAGCGTGACC 
               
               
                   
               
               
                 GTTAGCAGTGGCGGTGGTGGTAGCGGTGGTGGTGGTAGCGGTGGTGGTGG 
               
               
                   
               
               
                 CAGCGATATTCAAATGACCCAGAGCCCTGCCAGCCTGAGCGTGAGTGTTG 
               
               
                   
               
               
                 GCGAAACCGTGAGCATCACCTGCCGCGCCAGCGAGAACATCTATAGTAGC 
               
               
                   
               
               
                 CTGGCCTGGTACCAGCAGAAACAGGGCAAAAGCCCGCAGCTGCTGGTGTA 
               
               
                   
               
               
                 TAGCGCAACCATTCTGGCAGATGGCGTTCCGAGCCGTTTTAGCGGTAGCG 
               
               
                   
               
               
                 GCAGCGGCACACAGTACAGCCTGAAGATCAACAGCCTGCAGAGCGAGGAC 
               
               
                   
               
               
                 TTTGGCACCTATTACTGCCAGCACTTTTGGGGTACCCCGTATACCTTCGG 
               
               
                   
               
               
                 CGGCGGCACCAAACTGGAAATTAAATAA 
               
               
                   
               
               
                 Combined (SEQ ID NO. 29 and 30): 
               
               
                 gatatccagatgacccagtccccgagctccctgtccgcctctgtgggcga 
               
               
                 D  I  Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D 
               
               
                   
               
               
                 tagggtcaccatcacctgccgggcgagccaggatgtgaccaccgctgtag 
               
               
                  R  V  T  I  T  C  R  A  S  Q  D  V  T  T  A  V  A 
               
               
                   
               
               
                 cctggtatcaacagaaaccaggaaaagctccgaagcttctgatttactgg 
               
               
                   W  Y  Q  Q  K  P  G  K  A  P  K  L  L  I  Y  W 
               
               
                   
               
               
                 gcgagccgtcttcataatggcgtgccgagccgctttagcggcagcggctc 
               
               
                 A  S  R  L  H  N  G  V  P  S  R  F  S  G  S  G  S 
               
               
                   
               
               
                 cgggacggatttcactctgaccatcagcagtctgcagccggaagacttcg 
               
               
                  G  T  D  F  T  L  T  I  S  S  L  Q  P  E  D  F  A 
               
               
                   
               
               
                 caacttattactgtcagcaacattatagcaccccgctgacgttcggacag 
               
               
                   T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q 
               
               
                   
               
               
                 ggtaccaaggtggagatcaaacgtacggtggcagcaccgagcgtgtttat 
               
               
                 G  T  K  V  E  I  K  R  T  V  A  A  P  S  V  F  I 
               
               
                   
               
               
                 ctttccgccgagcgacgaacaactgaaaagtggcacagccagcgtggtgt 
               
               
                  F  P  P  S  D  E  Q  L  K  S  G  T  A  S  V  V  C 
               
               
                   
               
               
                 gtttactgaacaacttctatcctcgcgaggccaaggtgcagtggaaagtg 
               
               
                   L  L  N  N  F  Y  P  R  E  A  K  V  Q  W  K  V 
               
               
                   
               
               
                 gacaatgcactgcagagtggcaatagccaggagagcgtgaccgaacagga 
               
               
                 D  N  A  L  Q  S  G  N  S  Q  E  S  V  T  E  Q  D 
               
               
                   
               
               
                 tagcaaagatagcacctatagcctgagtagcaccctgaccctgagcaagg 
               
               
                  S  K  D  S  T  Y  S  L  S  S  T  L  T  L  S  K  A 
               
               
                   
               
               
                 ccgattatgagaagcacaaggtgtatgcatgcgaggttacccatcagggc 
               
               
                   D  Y  E  K  H  K  V  Y  A  C  E  V  T  H  Q  G 
               
               
                   
               
               
                 ctgagcagcccggtgaccaaaagctttaaccgtggcgaatgcggtggtag 
               
               
                 L  S  S  P  V  T  K  S  F  N  R  G  E  C  G  G  S 
               
               
                   
               
               
                 tggtggatccgcaggcagtgcaggtagtgccggcagcggtggtagtgagg 
               
               
                  G  G  S  A  G  S  A  G  S  A  G  S  G  G  S  E  V 
               
               
                   
               
               
                 ttcagctgcaggaaagcggcggcggcttaatgcagcctggcggtagcatg 
               
               
                   Q  L  Q  E  S  G  G  G  L  M  Q  P  G  G  S  M 
               
               
                   
               
               
                 aagctgagctgcgtggccagcggcttcacctttagcaattactggatgaa 
               
               
                 K  L  S  C  V  A  S  G  F  T  F  S  N  Y  W  M  N 
               
               
                   
               
               
                 ctgggtgcgccagagcccggaaaaaggcctggaatgggtggcagagatcc 
               
               
                  W  V  R  Q  S  P  E  K  G  L  E  W  V  A  E  I  R 
               
               
                   
               
               
                 gtctgaagagcaacaactacgccacccactatgccgaaagcgtgaagggt 
               
               
                   L  K  S  N  N  Y  A  T  H  Y  A  E  S  V  K  G 
               
               
                   
               
               
                 cgctttaccatcagccgcgatgacagcaaacgcagcgtgtatctgcagat 
               
               
                 R  F  T  I  S  R  D  D  S  K  R  S  V  Y  L  Q  M 
               
               
                   
               
               
                 gaacaccctgcgtgcagaggacaccggcatctattattgcacccgcggca 
               
               
                  N  T  L  R  A  E  D  T  G  I  Y  Y  C  T  R  G  N 
               
               
                   
               
               
                 acggtaattatcgcgccatggactactggggtcagggtaccagcgtgacc 
               
               
                   G  N  Y  R  A  M  D  Y  W  G  Q  G  T  S  V  T 
               
               
                   
               
               
                 gttagcagtggcggtggtggtagcggtggtggtggtagcggtggtggtgg 
               
               
                 V  S  S  G  G  G  G  S  G  G  G  G  S  G  G  G  G 
               
               
                   
               
               
                 cagcgatattcaaatgacccagagccctgccagcctgagcgtgagtgttg 
               
               
                  S  D  I  Q  M  T  Q  S  P  A  S  L  S  V  S  V  G 
               
               
                   
               
               
                 gcgaaaccgtgagcatcacctgccgcgccagcgagaacatctatagtagc 
               
               
                   E  T  V  S  I  T  C  R  A  S  E  N  I  Y  S  S 
               
               
                   
               
               
                 ctggcctggtaccagcagaaacagggcaaaagcccgcagctgctggtgta 
               
               
                 L  A  W  Y  Q  Q  K  Q  G  K  S  P  Q  L  L  V  Y 
               
               
                   
               
               
                 tagcgcaaccattctggcagatggcgttccgagccgttttagcggtagcg 
               
               
                  S  A  T  I  L  A  D  G  V  P  S  R  F  S  G  S  G 
               
               
                   
               
               
                 gcagcggcacacagtacagcctgaagatcaacagcctgcagagcgaggac 
               
               
                   S  G  T  Q  Y  S  L  K  I  N  S  L  Q  S  E  D 
               
               
                   
               
               
                 tttggcacctattactgccagcacttttggggtaccccgtataccttcgg 
               
               
                 F  G  T  Y  Y  C  Q  H  F  W  G  T  P  Y  T  F  G 
               
               
                   
               
               
                 cggcggcaccaaactggaaattaaataa 
               
               
                  G  G  T  K  L  E  I  K  - 
               
               
                   
               
               
                 F4-4G7 HC C′ Fusion Sequence-Amino Acid 
               
               
                 (SEQ ID NO: 31): 
               
               
                 EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY 
               
               
                   
               
               
                 IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL 
               
               
                   
               
               
                 YGNSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD 
               
               
                   
               
               
                 YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY 
               
               
                   
               
               
                 ICNVNHKPSNTKVDKKVEPKSCDKTHTCDKTHTCPPCPAPELLGRPSVFL 
               
               
                   
               
               
                 PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE 
               
               
                   
               
               
                 EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNAKLPAPIEKTISKAKGQP 
               
               
                   
               
               
                 REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT 
               
               
                   
               
               
                 TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL 
               
               
                   
               
               
                 SPGK   GGSAGSAGSAGSGGS   EVQLQESGPELEMPGASVKISKCASGSSFTG 
               
               
                   
               
               
                 FTGFSMNWVKQSNGKSLEWIGNIDTYYGGTTYNQKFKGKATLTVDKSSST 
               
               
                   
               
               
                 AYMQLKSLTSEDSAVYYCARSAYYGSTFAYWGQGTLVTVSA GGGGSGGGG   
               
               
                   
               
               
                   SGGGGS DIQMTQSPASLSASVGETVTITCRASENIYSYLAWYQQKQGKSP 
               
               
                   
               
               
                 QLLVYNAKTLIEGVPSRFSGSGSGTQFSLKINSLQPEDFGSYFCQHHFGT 
               
               
                   
               
               
                 PFTFGSGTELEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. 
     
       
         
           
               
            
               
                 Nucleotide (SEQ ID NO: 32): 
               
               
                 GAAGTTCAACTGGTTGAGAGTGGCGGTGGCTTAGTTCAACCGGGCGGTAG 
               
               
                   
               
               
                 TTTACGCCTGAGTTGTGCAGCCAGCGGTTTCGCCTTCAACTATTATGACA 
               
               
                   
               
               
                 TGTTTTGGGTGCGCCAGGCACCGGGTAAAGGCCTGGAGTGGGTGGCCTAT 
               
               
                   
               
               
                 ATCAAACCGGGCGGTGGCAACACCTATTACGCCGATAGCGTGAAAGGTCG 
               
               
                   
               
               
                 CTTTACCATCAGCGCAGATACCAGCAAGAATACCGCCTACCTGCAGATGA 
               
               
                   
               
               
                 ATAGCCTGCGTGCCGAAGACACCGCCGTTTATTATTGCGCCCGCCAGCTG 
               
               
                   
               
               
                 TACGGCAATAGCTTTTTCGATTACTGGGGCCAGGGCACCCTGGTTACCGT 
               
               
                   
               
               
                 TAGCAGCGCTAGCACCAAGGGTCCGAGCGTGTTTCCTCTGGCACCTAGCA 
               
               
                   
               
               
                 GTAAAAGCACCAGTGGTGGTACAGCAGCCCTGGGTTGCCTGGTGAAGGAT 
               
               
                   
               
               
                 TACTTTCCGGAGCCGGTGACCGTTAGTTGGAATAGCGGCGCCCTGACCAG 
               
               
                   
               
               
                 TGGCGTTCATACATTTCCGGCCGTGCTGCAGAGTAGTGGCCTGTACAGCC 
               
               
                   
               
               
                 TGAGTAGCGTTGTTACCGTTCCGAGCAGCAGCCTGGGCACCCAGACCTAT 
               
               
                   
               
               
                 ATTTGCAATGTTAACCATAAACCGAGCAACACAAAAGTTGATAAAAAAGT 
               
               
                   
               
               
                 TGAACCGAAGAGCTGTGACAAAACCCATACATGTGACAAAACACACACCT 
               
               
                   
               
               
                 GCCCGCCTTGTCCGGCACCTGAGCTGCTGGGTCGCCCGAGCGTTTTTCTG 
               
               
                   
               
               
                 TTTCCTCCGAAACCGAAAGACACCCTGATGATCAGCCGCACACCTGAGGT 
               
               
                   
               
               
                 GACCTGTGTTGTGGTGGATGTGAGCCACGAAGATCCTGAAGTTAAGTTTA 
               
               
                   
               
               
                 ACTGGTATGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGT 
               
               
                   
               
               
                 GAAGAGCAGTACAACAGCACCTATCGTGTTGTTAGTGTGCTGACCGTTCT 
               
               
                   
               
               
                 GCACCAAGATTGGCTGAACGGCAAGGAGTATAAATGCAAGGTTAGCAATA 
               
               
                   
               
               
                 AAGCCCTGCCGGCCCCGATCGAGAAGACCATCAGCAAAGCCAAAGGTCAG 
               
               
                   
               
               
                 CCGCGTGAGCCTCAGGTGTATACACTGCCGCCTAGCCGTGAGGAGATGAC 
               
               
                   
               
               
                 CAAGAATCAGGTTAGCCTGACCTGTCTGGTGAAAGGCTTTTACCCGAGCG 
               
               
                   
               
               
                 ATATCGCCGTTGAGTGGGAAAGCAATGGTCAGCCTGAGAACAACTACAAG 
               
               
                   
               
               
                 ACCACCCCGCCTGTTTTAGACAGTGATGGTAGCTTTTTCTTATACAGCAA 
               
               
                   
               
               
                 ACTGACCGTTGATAAGAGCCGCTGGCAGCAGGGCAATGTGTTTAGCTGCA 
               
               
                   
               
               
                 GTGTTATGCATGAGGCCCTGCATAACCACTATACCCAGAAGAGTCTGAGC 
               
               
                   
               
               
                 CTGAGTCCTGGCAAAGGTGGATCCGCCGGTAGCGCAGGCAGCGCAGGTAG 
               
               
                   
               
               
                 TGGTGGTAGCGAAGTTCAGCTGCAGGAAAGTGGCCCGGAACTGGAAATGC 
               
               
                   
               
               
                 CGGGCGCCAGCGTGAAAATCAGTTGCAAAGCCAGCGGTAGCAGCTTCACA 
               
               
                   
               
               
                 GGCTTCAGCATGAACTGGGTGAAGCAGAGCAACGGTAAGAGCCTGGAGTG 
               
               
                   
               
               
                 GATCGGCAACATTGACACCTACTATGGCGGCACCACCTACAACCAGAAGT 
               
               
                   
               
               
                 TCAAAGGCAAGGCCACCCTGACCGTGGATAAAAGCAGCAGCACAGCCTAC 
               
               
                   
               
               
                 ATGCAGCTGAAAAGCCTGACCAGCGAAGATAGCGCCGTGTATTACTGCGC 
               
               
                   
               
               
                 CCGTAGCGCCTATTACGGCAGCACCTTTGCATACTGGCAGGGTACCCTGG 
               
               
                   
               
               
                 TGACCGTGAGCGCAGGTGGTGGTGGTAGTGGTGGTGGTGGTAGCGGTGGT 
               
               
                   
               
               
                 GGCGGTAGTGACATTCAAATGACCCAGAGCCCTGCAAGCCTGAGCGCCAG 
               
               
                   
               
               
                 TGTTGGCGAAACCGTGACCATTACATGCCGCGCCAGCGAAAACATCTATA 
               
               
                   
               
               
                 GTTACCTGGCCTGGTACCAGCAGAAACAGGGCAAAAGCCCGCAACTGCTG 
               
               
                   
               
               
                 GTGTATAACGCCAAAACCCTGATTGAGGGCGTGCCGAGTCGCTTCAGCGG 
               
               
                   
               
               
                 TAGCGGTAGCGGTACACAGTTCAGTCTGAAAATCAACAGCCTGCAGCCGG 
               
               
                   
               
               
                 AAGACTTCGGCAGCTACTTTTGCCAGCACCACTTTGGCACCCCGTTTACA 
               
               
                   
               
               
                 TTTGGCAGCGGCACCGAGCTGGAAATTAAATAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 31 and 32): 
               
               
                 gaagttcaactggttgagagtggcggtggcttagttcaaccgggcggtag 
               
               
                 E  V  Q  L  V  E  S  G  G  G  L  V  Q  P  G  G  S 
               
               
                   
               
               
                 tttacgcctgagttgtgcagccagcggtttcgccttcaactattatgaca 
               
               
                  L  R  L  S  C  A  A  S  G  F  A  F  N  Y  Y  D  M 
               
               
                   
               
               
                 tgttttgggtgcgccaggcaccgggtaaaggcctggagtgggtggcctat 
               
               
                   F  W  V  R  Q  A  P  G  K  G  L  E  W  V  A  Y 
               
               
                   
               
               
                 atcaaaccgggcggtggcaacacctattacgccgatagcgtgaaaggtcg 
               
               
                 I  K  P  G  G  G  N  T  Y  Y  A  D  S  V  K  G  R 
               
               
                   
               
               
                 ctttaccatcagcgcagataccagcaagaataccgcctacctgcagatga 
               
               
                  F  T  I  S  A  D  T  S  K  N  T  A  Y  L  Q  M  N 
               
               
                   
               
               
                 atagcctgcgtgccgaagacaccgccgtttattattgcgcccgccagctg 
               
               
                   S  L  R  A  E  D  T  A  V  Y  Y  C  A  R  Q  L 
               
               
                   
               
               
                 tacggcaatagctttttcgattactggggccagggcaccctggttaccgt 
               
               
                 Y  G  N  S  F  F  D  Y  W  G  Q  G  T  L  V  T  V 
               
               
                   
               
               
                 tagcagcgctagcaccaagggtccgagcgtgtttcctctggcacctagca 
               
               
                  S  S  A  S  T  K  G  P  S  V  F  P  L  A  P  S  S 
               
               
                   
               
               
                 gtaaaagcaccagtggtggtacagcagccctgggttgcctggtgaaggat 
               
               
                   K  S  T  S  G  G  T  A  A  L  G  C  L  V  K  D 
               
               
                   
               
               
                 tactttccggagccggtgaccgttagttggaatagcggcgccctgaccag 
               
               
                 Y  F  P  E  P  V  T  V  S  W  N  S  G  A  L  T  S 
               
               
                   
               
               
                 tggcgttcatacatttccggccgtgctgcagagtagtggcctgtacagcc 
               
               
                  G  V  H  T  F  P  A  V  L  Q  S  S  G  L  Y  S  L 
               
               
                   
               
               
                 tgagtagcgttgttaccgttccgagcagcagcctgggcacccagacctat 
               
               
                   S  S  V  V  T  V  P  S  S  S  L  G  T  Q  T  Y 
               
               
                   
               
               
                 atttgcaatgttaaccataaaccgagcaacacaaaagttgataaaaaagt 
               
               
                 I  C  N  V  N  H  K  P  S  N  T  K  V  D  K  K  V 
               
               
                   
               
               
                 tgaaccgaagagctgtgacaaaacccatacatgtgacaaaacacacacct 
               
               
                  E  P  K  S  C  D  K  T  H  T  C  D  K  T  H  T  C 
               
               
                   
               
               
                 gcccgccttgtccggcacctgagctgctgggtcgcccgagcgtttttctg 
               
               
                   P  P  C  P  A  P  E  L  L  G  R  P  S  V  F  L 
               
               
                   
               
               
                 tttcctccgaaaccgaaagacaccctgatgatcagccgcacacctgaggt 
               
               
                 F  P  P  K  P  K  D  T  L  M  I  S  R  T  P  E  V 
               
               
                   
               
               
                 gacctgtgttgtggtggatgtgagccacgaagatcctgaagttaagttta 
               
               
                  T  C  V  V  V  D  V  S  H  E  D  P  E  V  K  F  N 
               
               
                   
               
               
                 actggtatgtggatggcgtggaggtgcataatgccaagacaaagccgcgt 
               
               
                   W  Y  V  D  G  V  E  V  H  N  A  K  T  K  P  R 
               
               
                   
               
               
                 gaagagcagtacaacagcacctatcgtgttgttagtgtgctgaccgttct 
               
               
                 E  E  Q  Y  N  S  T  Y  R  V  V  S  V  L  T  V  L 
               
               
                   
               
               
                 gcaccaagattggctgaacggcaaggagtataaatgcaaggttagcaata 
               
               
                  H  Q  D  W  L  N  G  K  E  Y  K  C  K  V  S  N  K 
               
               
                   
               
               
                 aagccctgccggccccgatcgagaagaccatcagcaaagccaaaggtcag 
               
               
                   A  L  P  A  P  I  E  K  T  I  S  K  A  K  G  Q 
               
               
                   
               
               
                 ccgcgtgagcctcaggtgtatacactgccgcctagccgtgaggagatgac 
               
               
                 P  R  E  P  Q  V  Y  T  L  P  P  S  R  E  E  M  T 
               
               
                   
               
               
                 caagaatcaggttagcctgacctgtctggtgaaaggcttttacccgagcg 
               
               
                  K  N  Q  V  S  L  T  C  L  V  K  G  F  Y  P  S  D 
               
               
                   
               
               
                 atatcgccgttgagtgggaaagcaatggtcagcctgagaacaactacaag 
               
               
                   I  A  V  E  W  E  S  N  G  Q  P  E  N  N  Y  K 
               
               
                   
               
               
                 accaccccgcctgttttagacagtgatggtagctttttcttatacagcaa 
               
               
                 T  T  P  P  V  L  D  S  D  G  S  F  F  L  Y  S  K 
               
               
                   
               
               
                 actgaccgttgataagagccgctggcagcagggcaatgtgtttagctgca 
               
               
                  L  T  V  D  K  S  R  W  Q  Q  G  N  V  F  S  C  S 
               
               
                   
               
               
                 gtgttatgcatgaggccctgcataaccactatacccagaagagtctgagc 
               
               
                   V  M  H  E  A  L  H  N  H  Y  T  Q  K  S  L  S 
               
               
                   
               
               
                 ctgagtcctggcaaaggtggatccgccggtagcgcaggcagcgcaggtag 
               
               
                 L  S  P  G  K  G  G  S  A  G  S  A  G  S  A  G  S 
               
               
                   
               
               
                 tggtggtagcgaagttcagctgcaggaaagtggcccggaactggaaatgc 
               
               
                  G  G  S  E  V  Q  L  Q  E  S  G  P  E  L  E  M  P 
               
               
                   
               
               
                 cgggcgccagcgtgaaaatcagttgcaaagccagcggtagcagcttcaca 
               
               
                   G  A  S  V  K  I  S  C  K  A  S  G  S  S  F  T 
               
               
                   
               
               
                 ggcttcagcatgaactgggtgaagcagagcaacggtaagagcctggagtg 
               
               
                 G  F  S  M  N  W  V  K  Q  S  N  G  K  S  L  E  W 
               
               
                   
               
               
                 gatcggcaacattgacacctactatggcggcaccacctacaaccagaagt 
               
               
                  I  G  N  I  D  T  Y  Y  G  G  T  T  Y  N  Q  K  F 
               
               
                   
               
               
                 tcaaaggcaaggccaccctgaccgtggataaaagcagcagcacagcctac 
               
               
                   K  G  K  A  T  L  T  V  D  K  S  S  S  T  A  Y 
               
               
                   
               
               
                 atgcagctgaaaagcctgaccagcgaagatagcgccgtgtattactgcgc 
               
               
                 M  Q  L  K  S  L  T  S  E  D  S  A  V  Y  Y  C  A 
               
               
                   
               
               
                 ccgtagcgcctattacggcagcacctttgcatactggcagggtaccctgg 
               
               
                  R  S  A  Y  Y  G  S  T  F  A  Y  W  Q  G  T  L  V 
               
               
                   
               
               
                 tgaccgtgagcgcaggtggtggtggtagtggtggtggtggtagcggtggt 
               
               
                   T  V  S  A  G  G  G  G  S  G  G  G  G  S  G  G 
               
               
                   
               
               
                 ggcggtagtgacattcaaatgacccagagccctgcaagcctgagcgccag 
               
               
                 G  G  S  D  I  Q  M  T  Q  S  P  A  S  L  S  A  S 
               
               
                   
               
               
                 tgttggcgaaaccgtgaccattacatgccgcgccagcgaaaacatctata 
               
               
                  V  G  E  T  V  T  I  T  C  R  A  S  E  N  I  Y  S 
               
               
                   
               
               
                 gttacctggcctggtaccagcagaaacagggcaaaagcccgcaactgctg 
               
               
                   Y  L  A  W  Y  Q  Q  K  Q  G  K  S  P  Q  L  L 
               
               
                   
               
               
                 gtgtataacgccaaaaccctgattgagggcgtgccgagtcgcttcagcgg 
               
               
                 V  Y  N  A  K  T  L  I  E  G  V  P  S  R  F  S  G 
               
               
                   
               
               
                 tagcggtagcggtacacagttcagtctgaaaatcaacagcctgcagccgg 
               
               
                  S  G  S  G  T  Q  F  S  L  K  I  N  S  L  Q  P  E 
               
               
                   
               
               
                 aagacttcggcagctacttttgccagcaccactttggcaccccgtttaca 
               
               
                   D  F  G  S  Y  F  C  Q  H  H  F  G  T  P  F  T 
               
               
                   
               
               
                 tttggcagcggcaccgagctggaaattaaata 
               
               
                 F  G  S  G  T  E  L  E  I  K  - 
               
               
                   
               
               
                 F4-4G7 LC C′ Fusion Sequence-Amino Acid 
               
               
                 (SEQ ID NO: 33): 
               
               
                 DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW 
               
               
                   
               
               
                 ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ 
               
               
                   
               
               
                 GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV 
               
               
                   
               
               
                 DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG 
               
               
                   
               
               
                 LSSPVTKSFNRGECGGS   GGSAGSAGSAGSGGS   EVQLQESGPELEMPGASV 
               
               
                   
               
               
                 KISCKASGSSFTGFSMNWVKQSNGKSLEWIGNIDTYYGGTTYNQKFKGKA 
               
               
                   
               
               
                 TLTVDKSSSTAYMQLKSLTSEDSAVYYCARSAYYGSTFAYWGQGLVTVSA 
               
               
                   
               
               
                   GGGGSGGGGSGGGGS DIQMTQSPASLSASVGETVTITCRASENIYSYLAW 
               
               
                   
               
               
                 YQQKQGKSPQLLVYNAKTLIEGVPSRFSGSGSGTQFSLKINSLQPEDFGS 
               
               
                   
               
               
                 YFCQHHFGTPFTFGSGTELEIKI 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide 
     
       
         
           
               
            
               
                 Nucleotide (SEQ ID NO: 34): 
               
               
                 GACATTCAGATGACCCAAAGTCCGAGCAGCCTGAGTGCCAGTGTTGGTGA 
               
               
                   
               
               
                 TCGCGTGACAATCACATGCAAGGCCAGTCAGGACGTGACCACCGCAGTGG 
               
               
                   
               
               
                 CCTGGTATCAGCAGAAACCGGGTAAGGCCCCGAAGCTGCTGATCTATTGG 
               
               
                   
               
               
                 GCCAGTACCCGCCACACCGGTGTTCCTAGTCGCTTCAGTGGCAGTGGCAG 
               
               
                   
               
               
                 CGGCACAGATTTCACCCTGACCATCAGCAGCCTGCAACCGGAAGATTTTG 
               
               
                   
               
               
                 CCACCTACTACTGCCAGCAGCACTATAGCACCCCGCTGACCTTTGGCCAG 
               
               
                   
               
               
                 GGCACCAAGGTTGAGATTAAACGTACGGTGGCAGCACCGAGCGTGTTTAT 
               
               
                   
               
               
                 CTTTCCGCCGAGCGACGAACAACTGAAAAGTGGCACAGCCAGCGTGGTGT 
               
               
                   
               
               
                 GTTTACTGAACAACTTCTATCCTCGCGAGGCCAAGGTGCAGTGGAAAGTG 
               
               
                   
               
               
                 GACAATGCACTGCAGAGTGGCAATAGCCAGGAGAGCGTGACCGAACAGGA 
               
               
                   
               
               
                 TAGCAAAGATAGCACCTATAGCCTGAGTAGCACCCTGACCCTGAGCAAGG 
               
               
                   
               
               
                 CCGATTATGAGAAGCACAAGGTGTATGCATGCGAGGTTACCCATCAGGGC 
               
               
                   
               
               
                 CTGAGCAGCCCGGTGACCAAAAGCTTTAACCGTGGCGAATGCGGTGGTAG 
               
               
                   
               
               
                 TGGTGGATCCGCCGGTAGCGCAGGCAGCGCAGGTAGTGGTGGTAGCGAAG 
               
               
                   
               
               
                 TTCAGCTGCAGGAAAGTGGCCCGGAACTGGAAATGCCGGGCGCCAGCGTG 
               
               
                   
               
               
                 AAAATCAGTTGCAAAGCCAGCGGTAGCAGCTTCACAGGCTTCAGCATGAA 
               
               
                   
               
               
                 CTGGGTGAAGCAGAGCAACGGTAAGAGCCTGGAGTGGATCGGCAACATTG 
               
               
                   
               
               
                 ACACCTACTATGGCGGCACCACCTACAACCAGAAGTTCAAAGGCAAGGCC 
               
               
                   
               
               
                 ACCCTGACCGTGGATAAAAGCAGCAGCACAGCCTACATGCAGCTGAAAAG 
               
               
                   
               
               
                 CCTGACCAGCGAAGATAGCGCCGTGTATTACTGCGCCCGTAGCGCCTATT 
               
               
                   
               
               
                 ACGGCAGCACCTTTGCATACTGGCAGGGTACCCTGGTGACCGTGAGCGCA 
               
               
                   
               
               
                 GGTGGTGGTGGTAGTGGTGGTGGTGGTAGCGGTGGTGGCGGTAGTGACAT 
               
               
                   
               
               
                 TCAAATGACCCAGAGCCCTGCAAGCCTGAGCGCCAGTGTTGGCGAAACCG 
               
               
                   
               
               
                 TGACCATTACATGCCGCGCCAGCGAAAACATCTATAGTTACCTGGCCTGG 
               
               
                   
               
               
                 TACCAGCAGAAACAGGGCAAAAGCCCGCAACTGCTGGTGTATAACGCCAA 
               
               
                   
               
               
                 AACCCTGATTGAGGGCGTGCCGAGTCGCTTCAGCGGTAGCGGTAGCGGTA 
               
               
                   
               
               
                 CACAGTTCAGTCTGAAAATCAACAGCCTGCAGCCGGAAGACTTCGGCAGC 
               
               
                   
               
               
                 TACTTTTGCCAGCACCACTTTGGCACCCCGTTTACATTTGGCAGCGGCAC 
               
               
                   
               
               
                 CGAGCTGGAAATTAAATAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 33 and 34): 
               
               
                 gacattcagatgacccaaagtccgagcagcctgagtgccagtgttggtga 
               
               
                 D  I  Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D 
               
               
                   
               
               
                 tcgcgtgacaatcacatgcaaggccagtcaggacgtgaccaccgcagtgg 
               
               
                  R  V  T  I  T  C  K  A  S  Q  D  V  T  T  A  V  A 
               
               
                   
               
               
                 cctggtatcagcagaaaccgggtaaggccccgaagctgctgatctattgg 
               
               
                   W  Y  Q  Q  K  P  G  K  A  P  K  L  L  I  Y  W 
               
               
                   
               
               
                 gccagtacccgccacaccggtgttcctagtcgcttcagtggcagtggcag 
               
               
                 A  S  T  R  H  T  G  V  P  S  R  F  S  G  S  G  S 
               
               
                   
               
               
                 cggcacagatttcaccctgaccatcagcagcctgcaaccggaagattttg 
               
               
                  G  T  D  F  T  L  T  I  S  S  L  Q  P  E  D  F  A 
               
               
                   
               
               
                 ccacctactactgccagcagcactatagcaccccgctgacctttggccag 
               
               
                   T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q 
               
               
                   
               
               
                 ggcaccaaggttgagattaaacgtacggtggcagcaccgagcgtgtttat 
               
               
                 G  T  K  V  E  I  K  R  T  V  A  A  P  S  V  F  I 
               
               
                   
               
               
                 ctttccgccgagcgacgaacaactgaaaagtggcacagccagcgtggtgt 
               
               
                  F  P  P  S  D  E  Q  L  K  S  G  T  A  S  V  V  C 
               
               
                   
               
               
                 gtttactgaacaacttctatcctcgcgaggccaaggtgcagtggaaagtg 
               
               
                   L  L  N  N  F  Y  P  R  E  A  K  V  Q  W  K  V 
               
               
                   
               
               
                 gacaatgcactgcagagtggcaatagccaggagagcgtgaccgaacagga 
               
               
                 D  N  A  L  Q  S  G  N  S  Q  E  S  V  T  E  Q  D 
               
               
                   
               
               
                 tagcaaagatagcacctatagcctgagtagcaccctgaccctgagcaagg 
               
               
                  S  K  D  S  T  Y  S  L  S  S  T  L  T  L  S  K  A 
               
               
                   
               
               
                 ccgattatgagaagcacaaggtgtatgcatgcgaggttacccatcagggc 
               
               
                   D  Y  E  K  H  K  V  Y  A  C  E  V  T  H  Q  G 
               
               
                   
               
               
                 ctgagcagcccggtgaccaaaagctttaaccgtggcgaatgcggtggtag 
               
               
                 L  S  S  P  V  T  K  S  F  N  R  G  E  C  G  G  S 
               
               
                   
               
               
                 tggtggatccgccggtagcgcaggcagcgcaggtagtggtggtagcgaag 
               
               
                  G  G  S  A  G  S  A  G  S  A  G  S  G  G  S  E  V 
               
               
                   
               
               
                 ttcagctgcaggaaagtggcccggaactggaaatgccgggcgccagcgtg 
               
               
                   Q  L  Q  E  S  G  P  E  L  E  M  P  G  A  S  V 
               
               
                   
               
               
                 aaaatcagttgcaaagccagcggtagcagcttcacaggcttcagcatgaa 
               
               
                 K  I  S  C  K  A  S  G  S  S  F  T  G  F  S  M  N 
               
               
                   
               
               
                 ctgggtgaagcagagcaacggtaagagcctggagtggatcggcaacattg 
               
               
                  W  V  K  Q  S  N  G  K  S  L  E  W  I  G  N  I  D 
               
               
                   
               
               
                 acacctactatggcggcaccacctacaaccagaagttcaaaggcaaggcc 
               
               
                   T  Y  Y  G  G  T  T  Y  N  Q  K  F  K  G  K  A 
               
               
                   
               
               
                 accctgaccgtggataaaagcagcagcacagcctacatgcagctgaaaag 
               
               
                 T  L  T  V  D  K  S  S  S  T  A  Y  M  Q  L  K  S 
               
               
                   
               
               
                 cctgaccagcgaagatagcgccgtgtattactgcgcccgtagcgcctatt 
               
               
                  L  T  S  E  D  S  A  V  Y  Y  C  A  R  S  A  Y  Y 
               
               
                   
               
               
                 acggcagcacctttgcatactggcagggtaccctggtgaccgtgagcgca 
               
               
                   G  S  T  F  A  Y  W  Q  G  T  L  V  T  V  S  A 
               
               
                   
               
               
                 ggtggtggtggtagtggtggtggtggtagcggtggtggcggtagtgacat 
               
               
                 G  G  G  G  S  G  G  G  G  S  G  G  G  G  S  D  I 
               
               
                   
               
               
                 tcaaatgacccagagccctgcaagcctgagcgccagtgttggcgaaaccg 
               
               
                  Q  M  T  Q  S  P  A  S  L  S  A  S  V  G  E  T  V 
               
               
                   
               
               
                 tgaccattacatgccgcgccagcgaaaacatctatagttacctggcctgg 
               
               
                   T  I  T  C  R  A  S  E  N  I  Y  S  Y  L  A  W 
               
               
                   
               
               
                 taccagcagaaacagggcaaaagcccgcaactgctggtgtataacgccaa 
               
               
                 Y  Q  Q  K  Q  G  K  S  P  Q  L  L  V  Y  N  A  K 
               
               
                   
               
               
                 aaccctgattgagggcgtgccgagtcgcttcagcggtagcggtagcggta 
               
               
                  T  L  I  E  G  V  P  S  R  F  S  G  S  G  S  G  T 
               
               
                   
               
               
                 cacagttcagtctgaaaatcaacagcctgcagccggaagacttcggcagc 
               
               
                   Q  F  S  L  K  I  N  S  L  Q  P  E  D  F  G  S 
               
               
                   
               
               
                 tacttttgccagcaccactttggcaccccgtttacatttggcagcggcac 
               
               
                 Y  F  C  Q  H  H  F  G  T  P  F  T  F  G  S  G  T 
               
               
                   
               
               
                 cgagctggaaattaaataa 
               
               
                  E  L  E  I  K  - 
               
               
                   
               
               
                 F4-4G7 LC C′ Fusion Sequence-Amino Acid 
               
               
                 (SEQ ID NO: 35): 
               
               
                 DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW 
               
               
                   
               
               
                 ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ 
               
               
                   
               
               
                 GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV 
               
               
                   
               
               
                 DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG 
               
               
                   
               
               
                 LSSPVTKSFNRGECGGS   GGSAGSAGSAGSGGS   EVQLQESGPELEMPGASV 
               
               
                   
               
               
                 KISCKASGSSFTGFSMNWVKQSNGKSLEWIGNIDTYYGGTTYNQKFKGKA 
               
               
                   
               
               
                 TLTVDKSSSTAYQMLKSLTSEDSAVYYCARSAYYGSTFAYWQGTLVTVSA 
               
               
                   
               
               
                   GGGGSGGGGSGGGGS DIQMTQSPASLSASVGETVTITCRASENIYSYLAW 
               
               
                   
               
               
                 YQQKQGKSPQLLVYNAKTLIEGVPSRFSGSGSGTQFSLKINSLQPEDFGS 
               
               
                   
               
               
                 YFCQHHFGTPFTFGSGTELEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 36): 
                   
               
               
                 GACATTCAGATGACCCAAAGTCCGAGCAGCCTGAGTGCCAGTGTTGGTGATCGC 
               
               
                   
               
               
                 GTGACAATCACATGCAAGGCCAGTCAGGACGTGACCACCGCAGTGGCCTGGTATCAQCAGA 
               
               
                   
               
               
                 TAGTCGCTTCAGTGGCAGTGGCAGCGGCACAGATTTCACCCTGACCATCAGCAGCCTGCAA 
               
               
                   
               
               
                 CCGGAAGATTTTGCCACCTACTACTGCCAGCAGCACTATAGCACCCCGCTGACCTTTGGCC 
               
               
                   
               
               
                 AGGGCACCAAGGTTGAGATTAAACGTACGGTGGCAGCACCGAGCGTGTTTATCTTTCCGCC 
               
               
                   
               
               
                 GAGCGACGAACAACTGAAAAGTGGCACAGCCAGCGTGGTGTGTTTACTGAACAACTTCTAT 
               
               
                   
               
               
                 CCTCGCGAGGCCAAGGTGCAGTGGAAAGTGGACAATGCACTGCAGAGTGGCAATAGCCAGG 
               
               
                   
               
               
                 AGAGCGTGACCGAACAGGATAGCAAAGATAGCACCTATAGCCTGAGTAGCACCCTGACCCT 
               
               
                   
               
               
                 GAGCAAGGCCGATTATGAGAAGCACAAGGTGTATGCATGCGAGGTTACCCATCAGGGCCTG 
               
               
                   
               
               
                 AGCAGCCCGGTGACCAAAAGCTTTAACCGTGGCGAATGCGGTGGTAGTGGTGGATCCGCCG 
               
               
                   
               
               
                 GTAGCGCAGGCAGCGCAGGTAGTGGTGGTAGCGAAGTTCAGCTGCAGGAAAGTGGCCCGGA 
               
               
                   
               
               
                 ACTGGAAATGCCGGGCGCCAGCGTGAAAATCAGTTGCAAAGCCAGCGGTAGCAGCTTCACA 
               
               
                   
               
               
                 GGCTTCAGCATGAACTGGGTGAAGCAGAGCAACGGTAAGAGCCTGGAGTGGATCGGCAACA 
               
               
                   
               
               
                 TTGACACCTACTATGGCGGCACCACCTACAACCAGAAGTTCAAAGGCAAGGCCACCCTGAC 
               
               
                   
               
               
                 CGTGGATAAAAGCAGCAGCACAGCCTACATSCAGCTGAAAAGCCTGACCAGCGAAGATAGC 
               
               
                   
               
               
                 GCCGTGTATTACTGCGCCCGTAGCGCCTATTACGGCAGCACCTTTGCATACTGGCAGGGTA 
               
               
                   
               
               
                 CCCTGGTGACCGTGAGCGCAGGTGGTGGTGGTAGTGGTGGTGGTGGTAGCGGTGGTGGCGG 
               
               
                   
               
               
                 TAGTGACATTCAAATGACCCAGAGCCCTGCAAGCCTGAGCGCCAGTGTTGGCGAAACCGTG 
               
               
                   
               
               
                 ACCATTACATGCCGCGCCAGCGAAAACATCTATAGTTACCTGGCCTGGTACCAGCAGAAAC 
               
               
                   
               
               
                 AGGGCAAAAGCCCGCAACTGCTGGTGTATAACGCCAAAACCCTGATTGAGGGCGTGCCGAG 
               
               
                   
               
               
                 TCGCTTCAGCGGTAGCGGTAGCGGTACACAGTTCAGTCTGAAAATCAACAGCCTGCAGCCG 
               
               
                   
               
               
                 GAAGACTTCGGCAGCTACTTTTGCCAGCACCACTTTGGCAGCCCGTTTACATTTGGCAGCG 
               
               
                   
               
               
                 GCACCGAGCTGGAAATTAAATAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 35 and 36): 
               
               
                 gacattcagatgacccaaagtccgagcagcctgagtgccagtgttggtgatcgcgtgaca 
               
               
                 D  I  Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T 
               
               
                   
               
               
                 atcacatgcaaggccagtcaggacgtgaccaccgcagtggcctggtatcagcagaaaccg 
               
               
                 I  T  C  K  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P 
               
               
                   
               
               
                 ggtaaggccccgaagctgctgatctattgggccagtacccgccacaccggtgttcctagt 
               
               
                 G  K  A  P  K  L  L  I  Y  W  A  S  T  R  H  T  G  V  P  S 
               
               
                   
               
               
                 cgcttcagtggcagtggcagcggcacagatttcaccctgaccatcagcagcctgcaaccg 
               
               
                 R  F  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P 
               
               
                   
               
               
                 gaagattttgccacctactactgccagcagcactatagcaccccgctgacctttggccag 
               
               
                 E  D  F  A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q 
               
               
                   
               
               
                 ggcaccaaggttgagattaaacgtacggtggcagcaccgagcgtgtttatctttccgccg 
               
               
                 G  T  K  V  E  I  K  R  T  V  A  A  P  S  V  F  I  F  P  P 
               
               
                   
               
               
                 agcgacgaacaactgaaaagtggcacagccagcgtggtgtgtttactgaacaacttctat 
               
               
                 S  D  E  Q  L  K  S  G  T  A  S  V  V  C  L  L  N  N  F  Y 
               
               
                   
               
               
                 cctcgcgaggccaaggtgcagtggaaagtggacaatgcactgcagagtggcaatagccag 
               
               
                 P  R  E  A  K  V  Q  W  K  V  D  N  A  L  Q  S  G  N  S  Q 
               
               
                   
               
               
                 gagagcgtgaccgaacaggatagcaaagatagcacctatagcctgagtagcaccctgacc 
               
               
                 E  S  V  T  E  Q  D  S  K  D  S  T  Y  S  L  S  S  T  L  T 
               
               
                   
               
               
                 ctgagcaaggccgattatgagaagcacaaggtgtatgcatgcgaggttacccatcagggc 
               
               
                 L  S  K  A  D  Y  E  K  H  K  V  Y  A  C  E  V  T  H  Q  G 
               
               
                   
               
               
                 ctgagcagcccggtgaccaaaagctttaaccgtggcgaatgcggtggtagtggtggatcc 
               
               
                 L  S  S  P  V  T  K  S  F  N  R  G  E  C  G  G  S  G  G  S 
               
               
                   
               
               
                 gccggtagcgcaggcagcgcaggtagtggtggtagcgaagttcagctgcaggaaagtggc 
               
               
                 A  G  S  A  G  S  A  G  S  G  G  S  E  V  Q  L  Q  E  S  G 
               
               
                   
               
               
                 ccggaactggaaatgccgggcgccagcgtgaaaatcagttgcaaagccagcggtagcagc 
               
               
                 P  E  L  E  M  P  G  A  S  V  K  I  S  C  K  A  S  G  S  S 
               
               
                   
               
               
                 ttcacaggcttcagcatgaactgggtgaagcagagcaacggtaagagcctggagtggatc 
               
               
                 F  T  G  F  S  M  N  W  V  K  Q  S  N  G  K  S  L  E  W  I 
               
               
                   
               
               
                 ggcaacattgacacctactatggcggcaccacctacaaccagaagttcaaaggcaaggcc 
               
               
                 G  N  I  D  T  Y  Y  G  G  T  T  Y  N  Q  K  F  K  G  K  A 
               
               
                   
               
               
                 accctgaccgtggataaaagcagcagcacagcctacatgcagctgaaaagcctgaccagc 
               
               
                 T  L  T  V  D  K  S  S  S  T  A  Y  M  Q  L  K  S  L  T  S 
               
               
                   
               
               
                 gaagatagcgccgtgtattactgcgcccgtagcgcctattacggcagcacctttgcatac 
               
               
                 E  D  S  A  V  Y  Y  C  A  R  S  A  Y  Y  G  S  T  F  A  Y 
               
               
                   
               
               
                 tggcagggtaccctggtgaccgtgagcgcaggtggtggtggtagtggtggtggtggtagc 
               
               
                 W  Q  G  T  L  V  T  V  S  A  G  G  G  G  S  G  G  G  G  S 
               
               
                   
               
               
                 ggtggtggcggtagtgacattcaaatgacccagagccctgcaagcctgagcgccagtgtt 
               
               
                 G  G  G  G  S  D  I  Q  M  T  Q  S  P  A  S  L  S  A  S  V 
               
               
                   
               
               
                 ggcgaaaccgtgaccattacatgccgcgccagcgaaaacatctatagttacctggcctgg 
               
               
                 G  E  T  V  T  I  T  C  R  A  S  E  N  I  Y  S  Y  L  A  W 
               
               
                   
               
               
                 taccagcagaaacagggcaaaagcccgcaactgctggtgtataacgccaaaaccctgatt 
               
               
                 Y  Q  Q  K  Q  G  K  S  P  Q  L  L  V  Y  N  A  K  T  L  I 
               
               
                   
               
               
                 gagggcgtgccgagtcgcttcagcggtagcggtagcggtacacagttcagtctgaaaatc 
               
               
                 E  G  V  P  S  R  F  S  G  S  G  S  G  T  Q  F  S  L  K  I 
               
               
                   
               
               
                 aacagcctgcagccggaagacttcggcagctacttttgccagcaccactttggcaccccg 
               
               
                 N  S  L  Q  P  E  D  F  G  S  Y  F  C  Q  H  H  F  G  T  P 
               
               
                   
               
               
                 tttacatttggcagcggcaccgagctggaaattaaataa 
               
               
                 F  T  F  G  S  G  T  E  L  E  I  K  - 
               
               
                   
               
               
                 E10-4G7 LC C′ Fusion Sequence - Amino Acid (SEQ ID NO: 37): 
               
               
                 DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYWASRL 
               
               
                   
               
               
                 HNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQGTKVEIKRTVAAPSV 
               
               
                   
               
               
                 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS 
               
               
                   
               
               
                 STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGS   GGSAGSAGSAGSGGS   EVQLQ 
               
               
                   
               
               
                 ESGPELEMPGASVKISCKASGSSFTGFSMNWVKQSNGKSLEWIGNIDTYYGGTTYNQKFKG 
               
               
                   
               
               
                 KATLTVDKSSSTAYMQLKSLTSEDSAVYYCARSAYYGSTFAYWQGTLVTVSA GGGGSGGGG   
               
               
                   
               
               
                   SGGGGS DIQMTQSPASLSASVGETVTITCRASENIYSYLAWYQQKQGKSPQLLVYNAKTLI 
               
               
                   
               
               
                 EGVPSRFSGSGSGTQFSLKINSLQPEDFGSYFCQHHFGTPFTFGSGTELEIK 
               
            
           
         
       
     
     Underlined region is glycine-rich linker polypeptide. Bold region is fusion linker polypeptide. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 38): 
                   
               
               
                 GATATCCAGATGACCCAGTCCCCGAGCTCCCTGTCCGCCTCTGTGGGCGATAGG 
               
               
                   
               
               
                 GTCACCATCACCTGCCGGGCGAGCCAGGATGTGACCACCGCTGTAGCCTGGTATCAACAGA 
               
               
                   
               
               
                 AACCAGGAAAAGCTCCGAAGCTTCTGATTTACTGGGCGAGCCGTCTTCATAATGGCGTGCC 
               
               
                   
               
               
                 GAGCCGCTTTAGCGGCAGCGGCTCCGGGACGGATTTCACTCTGACCATCAGCAGTCTGCAG 
               
               
                   
               
               
                 CCGGAAGACTTCGCAACTTATTACTGTCAGCAACATTATAGCACCCCGCTGACGTTCGGAC 
               
               
                   
               
               
                 AGGGTACCAAGGTGGAGATCAAACGTACGGTGGCAGCACCGAGCGTGTTTATCTTTCCGCC 
               
               
                   
               
               
                 GAGCGACGAACAACTGAAAAGTGGCACAGCCAGCGTGGTGTGTTTACTGAACAACTTCTAY 
               
               
                   
               
               
                 CCTCGCGAGGCCAAGGTGCAGTGGAAAGTGGACAATGCACTGCAGAGTGGCAATAGCCAGG 
               
               
                   
               
               
                 AGAGCGTGACCGAACAGGATAGCAAAGATAGCACCTATAGCCTGAGTAGCACCCTGACCCT 
               
               
                   
               
               
                 GAGCAAGGCCGATTATGAGAAGCACAAGGTGTATGCATGCGAGGTTACCCATCAGGGCCTG 
               
               
                   
               
               
                 AGCAGCCCGGTGACCAAAAGCTTTAACCGTGGCGAATGCGGTGGTAGTGGTGGATCCGCCG 
               
               
                   
               
               
                 GTAGCGCAGGCAGCGCAGGTAGTGGTGGTAGCGAAGTTCAGCTGCAGGAAAGTGGCCCGGA 
               
               
                   
               
               
                 ACTGGAAATGCCGGGCGCCAGCGTGAAAATCAGTTGCAAAGCCAGCGGTAGCAGCTTCACA 
               
               
                   
               
               
                 GGCTTCAGCATGAACTGGGTGAAGCAGAGCAACGGTAAGAGCCTGGAGTGGATCGGCAACA 
               
               
                   
               
               
                 TTGACACCTACTATGGCGGCACCACCTACAACCAGAAGTTCAAAGGCAAGGCCACCCTGAC 
               
               
                   
               
               
                 CGTGGATAAAAGCAGCAGCACAGCCTACATGCAGCTGAAAAGCCTGACCAGCGAAGATAGC 
               
               
                   
               
               
                 GCCGTGTATTACTGCGCCCGTAGCGCCTATTACGGCAGCACCTTTGCATACTGCCAQGGTA 
               
               
                   
               
               
                 CCCTGGTGACCGTGAGCGCAGGTGOTGGTGGTAGTGGTGGTGGTGGTAGCGGTGGTGGCGG 
               
               
                   
               
               
                 TAGTGACATTCAAATGACCCAGAGCCCTGCAAGCCTGAGCGCCAGTGTTGGCGAAACCGTG 
               
               
                   
               
               
                 ACCATTACATGCCGCGCCAGCGAAAACATCTATAGTTACCTGGCCTGGTACCAGCAGAAAC 
               
               
                   
               
               
                 AGGGCAAAAGCCCGCAACTGCTGGTGTATAACGCCAAAACCCTGATTGAGGGCGTGCCGAG 
               
               
                   
               
               
                 TCGCTTCAGCGGTAGCGGTAGCGGTACACAGTTCAGTCTGAAAATCAACAGCCTGCAGCCG 
               
               
                   
               
               
                 GAAGACTTCGGCAGCTACTTTTGCCAGCACCACTTTGGCACCCCGTTTACATTTGGCAGCG 
               
               
                   
               
               
                 GCACCGAGCTGGAAATTAAATAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 37 and 38): 
               
               
                 gatatccagatgacccagtccccgagctccctgtccgcctctgtgggcgatagggtcacc 
               
               
                 D  I  Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T 
               
               
                   
               
               
                 atcacctgccgggcgagccaggatgtgaccaccgctgtagcctggtatcaacagaaacca 
               
               
                 I  T  C  R  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P 
               
               
                   
               
               
                 ggaaaagctccgaagcttctgatttactgggcgagccgtcttcataatggcgtgccgagc 
               
               
                 G  K  A  P  K  L  L  I  Y  W  A  S  R  L  H  N  G  V  P  S 
               
               
                   
               
               
                 cgctttagcggcagcggctccgggacggatttcactctgaccatcagcagtctgcagccg 
               
               
                 R  F  S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P 
               
               
                   
               
               
                 gaagacttcgcaacttattactgtcagcaacattatagcaccccgctgacgttcggacag 
               
               
                 E  D  F  A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q 
               
               
                   
               
               
                 ggtaccaaggtggagatcaaacgtacggtggcagcaccgagcgtgtttatctttccgccg 
               
               
                 G  T  K  V  E  I  K  R  T  V  A  A  P  S  V  F  I  F  P  P 
               
               
                   
               
               
                 agcgacgaacaactgaaaagtggcacagccagcgtggtgtgtttactgaacaacttctat 
               
               
                 S  D  E  Q  L  K  S  G  T  A  S  V  V  C  L  L  N  N  F  Y 
               
               
                   
               
               
                 cctcgcgaggccaaggtgcagtggaaagtggacaatgcactgcagagtggcaatagccag 
               
               
                 P  R  E  A  K  V  Q  W  K  V  D  N  A  L  Q  S  G  N  S  Q 
               
               
                   
               
               
                 gagagcgtgaccgaacaggatagcaaagatagcacctatagcctgagtagcaccctgacc 
               
               
                 E  S  V  T  E  Q  D  S  K  D  S  T  Y  S  L  S  S  T  L  T 
               
               
                   
               
               
                 ctgagcaaggccgattatgagaagcacaaggtgtatgcatgcgaggttacccatcagggc 
               
               
                 L  S  K  A  D  Y  E  K  H  K  V  Y  A  C  E  V  T  H  Q  G 
               
               
                   
               
               
                 ctgagcagcccggtgaccaaaagctttaaccgtggcgaatgcggtggtagtggtggatcc 
               
               
                 L  S  S  P  V  T  K  S  F  N  R  G  E  C  G  G  S  G  G  S 
               
               
                   
               
               
                 gccggtagcgcaggcagcgcaggtagtggtggtagcgaagttcagctgcaggaaagtggc 
               
               
                 A  G  S  A  G  S  A  G  S  G  G  S  E  V  Q  L  Q  E  S  G 
               
               
                   
               
               
                 ccggaactggaaatgccgggcgccagcgtgaaaatcagttgcaaagccagcggtagcagc 
               
               
                 P  E  L  E  M  P  G  A  S  V  K  I  S  C  K  A  S  G  S  S 
               
               
                   
               
               
                 ttcacaggcttcagcatgaactgggtgaagcagagcaacggtaagagcctggagtggatc 
               
               
                 F  T  G  F  S  M  N  W  V  K  Q  S  N  G  K  S  L  E  W  I 
               
               
                   
               
               
                 ggcaacattgacacctactatggcggcaccacctacaaccagaagttcaaaggcaaggcc 
               
               
                 G  N  I  D  T  Y  Y  G  G  T  T  Y  N  Q  K  F  K  G  K  A 
               
               
                   
               
               
                 accctgaccgtggataaaagcagcagcacagcctacatgcagctgaaaagcctgaccagc 
               
               
                 T  L  T  V  D  K  S  S  S  T  A  Y  M  Q  L  K  S  L  T  S 
               
               
                   
               
               
                 gaagatagcgccgtgtattactgcgcccgtagcgcctattacggcagcacctttgcatac 
               
               
                 E  D  S  A  V  Y  Y  C  A  R  S  A  Y  Y  G  S  T  F  A  Y 
               
               
                   
               
               
                 tggcagggtaccctggtgaccgtgagcgcaggtggtggtggtagtggtggtggtggtagc 
               
               
                 W  Q  G  T  L  V  T  V  S  A  G  G  G  G  S  G  G  G  G  S 
               
               
                   
               
               
                 ggtggtggcggtagtgacattcaaatgacccagagccctgcaagcctgagcgccagtgtt 
               
               
                 G  G  G  G  S  D  I  Q  M  T  Q  S  P  A  S  L  S  A  S  V 
               
               
                   
               
               
                 ggcgaaaccgtgaccattacatgccgcgccagcgaaaacatctatagttacctggcctgg 
               
               
                 G  E  T  V  T  I  T  C  R  A  S  E  N  I  Y  S  Y  L  A  W   
               
               
                   
               
               
                 taccagcagaaacagggcaaaagcccgcaactgctggtgtataacgccaaaaccctgatt 
               
               
                 Y  Q  Q  K  Q  G  K  S  P  Q  L  L  V  Y  N  A  K  T  L  I 
               
               
                   
               
               
                 gagggcgtgccgagtcgcttcagcggtagcggtagcggtacacagttcagtctgaaaatc 
               
               
                 E  G  V  P  S  R  F  S  G  S  G  S  G  T  Q  G  S  L  K  I 
               
               
                   
               
               
                 aacagcctgcagccggaagacttcggcagctacttttgccagcaccactttggcaccccg 
               
               
                 N  S  L  Q  P  E  D  F  G  S  Y  F  C  Q  H  H  F  G  T  P 
               
               
                   
               
               
                 tttacatttggcagcggcaccgagctggaaattaaataa 
               
               
                 F  T  F  G  S  G  T  E  L  E  I  K - 
               
            
           
         
       
     
     In an embodiment of any of the antibodies and/or scFv described herein (of the compositions described herein), the antibody and/or scFv is a neutralizing antibody/scFv with respect to the relevant Ebola virus. 
     In an embodiment, the antibody or scFv binds the relevant Ebola virus glycoprotein pre-fusion core, which is a heterohexamer of three copies of the GP1 and 3 copies of the GP2. 
     Exemplary Dual-Variable Domain (DVD) Bispecifics Sequences: the following exemplary DVD amino acid sequences (LC and HC) are provided, for the compositions of the invention as relating to the embodiments of antibodies E10, F4, KZ52, and 13C6 with non-limiting exemplary nucleotide sequences (in view of the degeneracy of the genetic code). The DVD constructs are dual-specific, tetravalent immunoglobulin G (IgG)-like molecules, termed dual-variable-domain immunoglobulin. In an embodiment, the sequences of the DVD except for the first and second linker amino acid sequences (such as the CDRs, the CH regions, the hinge regions, the CL region, sequences) are based on human IgG sequences). 
     
       
         
           
               
            
               
                 E10-KZ52 HC DVD Fusion sequence - Amino Acid 
               
               
                 (SEQ ID NO 43): 
               
               
                 EVQLLESGGGLVKPGGSLRLSCAASGFTLINYRMNWVRQAPGKGLEWVSSI 
               
               
                   
               
               
                 SSSSSYIHYADSVKGRFTISRDNAENSLYLQMNSLRAEDTAVYYCVREGPR 
               
               
                   
               
               
                 ATGYSMADVFDIWGQGTMVTVSS   EVQLVESGGGLVQPGGSLRL 
               
               
                   
               
               
                 SCAASGFAFNYYDIHWVRQAPGKGLEWVAYINPGGGNTYYADSVKGRFTIS 
               
               
                   
               
               
                 ADTSKNTAYLQMNSLRAEDTAVYYCARQLYGNSFMDYWGQGTLVTVSS 
               
            
           
         
       
     
     Underlined bold region is amino acid linker sequence. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 44): 
                   
               
               
                 GAAGTGCAGCTGCTGGAAAGCGGCGGTGGCCTGGTGAAACCGGGTG 
               
               
                   
               
               
                 GTAGTCTGCGCCTGAGTTGCGCCGCCAGCGGTTTTACCCTGATCAACTACCGCA 
               
               
                   
               
               
                 TGAACTGGGTGCGTCAGGCCCCGGGCAAAGGTCTGGAGTGGGTTAGTAGCATC 
               
               
                   
               
               
                 AGCAGTAGCAGCAGCTACATCCATTACGCCGACAGCGTGAAAGGCCGTTTCAC 
               
               
                   
               
               
                 CATCAGTCGCGATAACGCCGAGAATAGCCTGTACCTGCAGATGAACAGCCTGC 
               
               
                   
               
               
                 GTGCAGAAGATACCGCCGTGTATTACTGCGTGCGCGAAGGTCCGCGTGCAACC 
               
               
                   
               
               
                 GGTTATAGCATGGCCGATGTGTTCGATATTTGGGGCCAGGGTACCATGGTGACC 
               
               
                   
               
               
                 GTGAGCAGTGCCAGCACCAAAGGTCCGGAAGTTCAGCTGGTGGAAAGCGGTGG 
               
               
                   
               
               
                 TGGTCTGGTTCAGCCGGGTGGTAGCTTACGTCTGAGCTGCGCAGCCAGCGGCTT 
               
               
                   
               
               
                 TGCCTTCAATTATTATGATATTCATTGGGTCGCCAAGCCCCGGGCAAGGGCCT 
               
               
                   
               
               
                 GGAATGGGTGGCATATATCAATCCGGGTGGCGGCAACACCTATTATGCCGATA 
               
               
                   
               
               
                 GCGTGAAGGGTCGCTTTACCATCAGCGCCGATACCAGCAAGAACACCGCCTATC 
               
               
                   
               
               
                 TGCAGATGAATAGCTTACGTGCTGAAGATACAGCCGTTTACTACTGTGCCCGCC 
               
               
                   
               
               
                 AGCTGTATGGCAACAGCTTCATGGATTATTGGGGCCAAGGCACCCTGGTGACCG 
               
               
                   
               
               
                 TTAGCAGC 
               
               
                   
               
               
                 Combined (SEQ ID NOS: 43 and 44):  
               
               
                 gaagtgcagctgctggaaagcggcggtggcctggtgaaaccgggtggtagtctgcgcctg 
               
               
                 E  V  Q  L  L  E  S  G  G  G  L  V  K  P  G  G  S  L  R  L 
               
               
                   
               
               
                 agttgcgccgccagcggttttaccctgatcaactaccgcatgaactgggtgcgtcaggcc 
               
               
                 S  C  A  A  S  G  F  T  L  I  N  Y  R  M  N  W  V  R  Q  A 
               
               
                   
               
               
                 ccgggcaaaggtctggagtgggttagtagcatcagcagtagcagcagctacatccattac 
               
               
                 P  G  K  G  L  E  W  V  S  S  I  S  S  S  S  S  Y  I  H  Y 
               
               
                   
               
               
                 gccgacagcgtgaaaggccgtttcaccatcagtcgcgataacgccgagaatagcctgtac 
               
               
                 A  D  S  V  K  G  R  F  T  I  S  R  D  N  A  E  N  S  L  Y 
               
               
                   
               
               
                 ctgcagatgaacagcctgcgtgcagaagataccgccgtgtattactgcgtgcgcgaaggt 
               
               
                 L  Q  M  N  S  L  R  A  E  D  T  A  V  Y  Y  C  V  R  E  G 
               
               
                   
               
               
                 ccgcgtgcaaccggttatagcatggccgatgtgttcgatatttggggccagggtaccatg 
               
               
                 P  R  A  T  G  Y  S  M  A  D  V  F  D  I  W  G  Q  G  T  M 
               
               
                   
               
               
                 gtgaccgtgagcagtgccagcaccaaaggtccggaagttcagctggtggaaagcggtggt 
               
               
                 V  T  V  S  S  A  S  T  K  G  P  E  V  Q  L  V  E  S  G  G 
               
               
                   
               
               
                 ggtctggttcagccgggtggtagcttacgtctgagctgcgcagccagcggctttgccttc 
               
               
                 G  L  V  Q  P  G  G  S  L  R  L  S  C  A  A  S  G  F  A  F 
               
               
                   
               
               
                 aattattatgatattcattgggttcgccaagccccgggcaagggcctggaatgggtggca 
               
               
                 N  Y  Y  D  I  H  W  V  R  Q  A  P  G  K  G  L  E  W  V  A 
               
               
                   
               
               
                 tatatcaatccgggtggcggcaacacctattatgccgatagcgtgaagggtcgctttacc 
               
               
                 Y  I  N  P  G  G  G  N  T  Y  Y  A  D  S  V  K  G  R  F  T 
               
               
                   
               
               
                 atcagcgccgataccagcaagaacaccgcctatctgcagatgaatagcttacgtgctgaa 
               
               
                 I  S  A  D  T  S  K  N  T  A  Y  L  Q  M  N  S  L  R  A  E 
               
               
                   
               
               
                 gatacagccgtttactactgtgcccgccagctgtatggcaacagcttcatggattattgg 
               
               
                 D  T  A  V  Y  Y  C  A  R  Q  L  Y  G  N  S  F  M  D  Y  W 
               
               
                   
               
               
                 ggccaaggcaccctggtgaccgttagcagc 
               
               
                 G  Q  G  T  L  V  T  V  S  S 
               
               
                   
               
               
                 E10-KZ52 LC DVD Fusion sequence - Amino Acid (SEQ ID NO: 45): 
               
               
                 ELVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKSYLAWYQQKPGQPPKLLIYW 
               
               
                   
               
               
                 ASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSAPLTFGGGTKVEIK 
               
               
                   
               
               
                    DIQMTQSPSSLSASVGDRVTITCRASQDVTTAVAWYQQKPGKAPKLLIYW 
               
               
                   
               
               
                 ASRLHNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQGTKVEIK 
               
            
           
         
       
     
     Underlined bold region is amino acid linker sequence. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 46): 
                   
               
               
                 GAACTGGTGATGACCCAGAGCCCGGATAGCCTGGCAGTTAGTCTGGG 
               
               
                   
               
               
                 CGAACGCGCCACCATTAACTGCAAAAGCAGCCAGAGCGTGCTGTATAGCAGCA 
               
               
                   
               
               
                 ATAATAAAAGCTATCTGGCATGGTACCAGCAGAAACCGGGTCAGCCGCCGAAG 
               
               
                   
               
               
                 CTGCTGATCTACTGGGCAAGCACCCGTGAAAGTGGTGTTCCGGATCGCTTTAGC 
               
               
                   
               
               
                 GGCAGCGGCAGCGGTACAGATTTCACCCTGACCATTAGCAGCCTGCAGGCCGA 
               
               
                   
               
               
                 AGATGTGGCAGTGTATTACTGCCAGCAGTACTATAGCGCACCGCTGACCTTTGG 
               
               
                   
               
               
                 TGGCGGCACCAAAGTGGAAATTAAGACCGTGGCCGCACCGGATATTCAGATGA 
               
               
                   
               
               
                 CCCAAAGCCCGAGCAGCCTGAGCTGCAAGCGTGGGTGATCGTGTGACAATTACC 
               
               
                   
               
               
                 TGCCGCGCAAGCCAGGATGTGACCACCGCCGTGGCATGGTATCAACAGAAACC 
               
               
                   
               
               
                 GGGCAAAGCCCCGAAACTGCTGATTTATTGGGCCAGCCGCCTGCATAATGGCGT 
               
               
                   
               
               
                 TCCGAGCCGCTTCAGCGGTAGCGGTAGCGGTACCGACTTTACCCTGACCATTAG 
               
               
                   
               
               
                 CAGTCTGCAGCCGGAGGATTTTGCCACCTACTACTGTCAGCAGCACTATAGCAC 
               
               
                   
               
               
                 CCCTCTGACCTTTGGCCAGGGCACCAAGGTGGAAATCAAA 
               
               
                   
               
               
                 Combined (SEQ ID NO: 45 and 46): 
               
               
                 gaactggtgatgacccagagcccggatagcctggcagttagtctgggcgaacgcgccacc 
               
               
                 E  L  V  M  T  Q  S  P  D  S  L  A  V  S  L  G  E  R  A  T 
               
               
                   
               
               
                 attaactgcaaaagcagccagagcgtgctgtatagcagcaataataaaagctatctggca 
               
               
                 I  N  C  K  S  S  Q  S  V  L  Y  S  S  N  N  K  S  Y  L  A 
               
               
                   
               
               
                 tggtaccagcagaaaccgggtcagccgccgaagctgctgatctactgggcaagcacccgt 
               
               
                 W  Y  Q  Q  K  P  G  Q  P  P  K  L  L  I  Y  W  A  S  T  R 
               
               
                   
               
               
                 gaaagtggtgttccggatcgctttagcggcagcggcagcggtacagatttcaccctgacc 
               
               
                 E  S  G  V  P  D  R  F  S  G  S  G  S  G  T  D  F  T  L  T 
               
               
                   
               
               
                 attagcagcctgcaggccgaagatgtggcagtgtattactgccagcagtactatagcgca 
               
               
                 I  S  S  L  Q  A  E  D  V  A  V  Y  Y  C  Q  Q  Y  Y  S  A 
               
               
                   
               
               
                 ccgctgacctttggtggcggcaccaaagtggaaattaagaccgtggccgcaccggatatt 
               
               
                 P  L  T  F  G  G  G  T  K  V  E  I  K  T  V  A  A  P  D  I 
               
               
                   
               
               
                 cagatgacccaaagcccgagcagcctgagtgcaagcgtgggtgatcgtgtgacaattacc 
               
               
                 Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T  I  T 
               
               
                   
               
               
                 tgccgcgcaagccaggatgtgaccaccgccgtggcatggtatcaacagaaaccgggcaaa 
               
               
                 C  R  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P  G  K 
               
               
                   
               
               
                 gccccgaaactgctgatttattgggccagccgcctgcataatggcgttccgagccgcttc 
               
               
                 A  P  K  L  L  I  Y  W  A  S  R  L  H  N  G  V  P  S  R  F 
               
               
                   
               
               
                 agcggtagcggtagcggtaccgactttaccctgaccattagcagtctgcagccggaggat 
               
               
                 S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P  E  D 
               
               
                   
               
               
                 tttgccacctactactgtcagcagcactatagcacccctctgacctttggccagggcacc 
               
               
                 F  A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q  G  T 
               
               
                   
               
               
                 aaggtggaaatcaaa 
               
               
                 R  V  E  I  K 
               
               
                   
               
               
                 F4-KZ52 HC DVD Fusion sequence - Amino Acid (SEQ ID NO: 47): 
               
               
                 EVQLLESGGGLVKPGGSLRLSCAASGFTLINYRMNWVRQAPGKGLEWV 
               
               
                   
               
               
                 SSISSSSSYIHYADSVKGRFTISRDNAENSLYLQMNSLRAEDTAVYYCVREGPRATG 
               
               
                   
               
               
                 YSMADVFDIWGQGTMVTVSS   EVQLVESGGGLVQPGGSLRLSCAASGFAF 
               
               
                   
               
               
                 NYYDMFWVRQAPGKGLEWVAYIKPGGGNTYYADSVKGRFTISADTSKNTAYLQM 
               
               
                   
               
               
                 NSLRAEDTAVYYCARQLYGNSFFDYWGQGTLVTVSS 
               
            
           
         
       
     
     Underlined bold region is amino acid linker sequence. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 48): 
                   
               
               
                 GAGGTGCAGCTGCTGGAGAGCGGTGGTGGTCTGGTGAAACCGGGCG 
               
               
                   
               
               
                 GTAGCTTACGCCTGAGTTGCGCCGCAAGCGGTTTTACCCTGATCAACTACCGCA 
               
               
                   
               
               
                 TGAACTGGGTTCGTCAGGCCCCGGGCAAGGGTCTGGAATGGGTGAGCAGCATT 
               
               
                   
               
               
                 AGCAGCAGCAGCAGCTACATCCACTACGCCGATAGCGTGAAAGGTCGCTTCAC 
               
               
                   
               
               
                 CATCAGCCGCGACAATGCCGAAAACAGCCTGTATCTGCAGATGAACAGCTTAC 
               
               
                   
               
               
                 GCGCCGAAGATACCGCCGTGTACTATTGCGTTCGTGAGGGTCCGCGTGCAACCG 
               
               
                   
               
               
                 GCTATAGCATGGCCGACGTGTTCGATATCTGGGGTCAGGGCACCATGGTGACCG 
               
               
                   
               
               
                 TTAGCAGCGCCAGCACCAAAGGTCCGGAAGTGCAACTGGTGGAAAGTGGCGGT 
               
               
                   
               
               
                 GGTCTGGTGCAGCCGGGTGGTAGTCTGCGCCTGAGCTGTGCCGCAAGCGGCTTT 
               
               
                   
               
               
                 GCCTTTATTATTATGATATGTTTTGGGTGCGCCAGGCACCGGGCAAAGGTCTG 
               
               
                   
               
               
                 GAGTGGGTGGCCTACATTAAGCCGGGCGGTGGCAATACCTATTATGCCGACAG 
               
               
                   
               
               
                 CGTGAAGGGCCGCTTTACCATCAGCGCCGACACCAGCAAAAACACCGCCTACC 
               
               
                   
               
               
                 TGCAAATGAATAGCTTACGTGCTGAAGACACCGCAGTTTATTATTGCGCCCGCC 
               
               
                   
               
               
                 AGCTGTATGGCAATAGCTTCTTCGACTATTGGGGCCAAGGCACCCTGGTGACAG 
               
               
                   
               
               
                 TTAGCAGC 
               
               
                   
               
               
                 Combined (SEQ ID NO: 47 and 48): 
               
               
                 gaggtgcagctgctggagagcggtggtggtctggtgaaaccgggcggtagcttacgcctg 
               
               
                 E  V  Q  L  L  E  S  G  G  G  L  V  K  P  G  G  S  L  R  L 
               
               
                   
               
               
                 agttgcgccgcaagcggttttaccctgatcaactaccgcatgaactgggttcgtcaggcc 
               
               
                 S  C  A  A  S  G  F  T  L  I  N  Y  R  M  N  W  V  R  Q  A 
               
               
                   
               
               
                 ccgggcaagggtctggaatgggtgagcagcattagcagcagcagcagctacatccactac 
               
               
                 P  G  K  G  L  E  W  V  S  S  I  S  S  S  S  S  Y  I  H  Y 
               
               
                   
               
               
                 gccgatagcgtgaaaggtcgcttcaccatcagccgcgacaatgccgaaaacagcctgtat 
               
               
                 A  D  S  V  K  G  R  F  T  I  S  R  D  N  A  E  N  S  L  Y 
               
               
                   
               
               
                 ctgcagatgaacagcttacgcgccgaagataccgccgtgtactattgcgttcgtgagggt 
               
               
                 L  Q  M  N  S  L  R  A  E  D  T  A  V  Y  Y  C  V  R  E  G 
               
               
                   
               
               
                 ccgcgtgcaaccggctatagcatggccgacttgttcgatatctggggtcagggcaccatg 
               
               
                 P  R  A  T  G  Y  S  M  A  D  V  F  D  I  W  G  Q  G  T  M 
               
               
                   
               
               
                 gtgaccgttagcagcgccagcaccaaaggtccggaagtgcaactggtggaaagtggcggt 
               
               
                 V  T  V  S  S  A  S  T  K  G  P  E  V  Q  L  V  E  S  G  G 
               
               
                   
               
               
                 ggtctggtgcagccgggtggtagtctgcgcctgagctgtgccgcaagcggctttgccttt 
               
               
                 G  L  V  Q  P  G  G  S  L  R  L  S  C  A  A  S  G  F  A  F 
               
               
                   
               
               
                 aattattatgatatgttttgggtgcgccaggcaccgggcaaaggtctggagtgggtggcc 
               
               
                 N  Y  Y  D  M  F  W  V  R  Q  A  P  G  K  G  L  E  W  V  A 
               
               
                   
               
               
                 tacattaagccgggcggtggcaatacctattatgccgacagcgtgaagggccgctttacc 
               
               
                 Y  I  K  P  G  G  G  N  T  Y  Y  A  D  S  V  K  G  R  F  T 
               
               
                   
               
               
                 atcagcgccgacaccagcaaaaacaccgcctacctgcaaatgaatagcttagctgctgaa 
               
               
                 I  S  A  D  T  S  K  N  T  A  Y  L  Q  M  N  S  L  R  A  E 
               
               
                   
               
               
                 gacaccgcagtttattattgcgcccgccagctgtatggcaatagcttcttcgactattgg 
               
               
                 D  T  A  V  Y  Y  C  A  R  Q  L  Y  G  N  S  F  F  D  Y  W 
               
               
                   
               
               
                 ggccaaggcaccctggtgacagttagcagc 
               
               
                 G  Q  G  T  L  V  T  V  S  S 
               
               
                   
               
               
                 F4-KZ52 LC DVD Fusion sequence - Amino Acid (SEQ ID NO: 49): 
               
               
                 ELVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKSYLAWYQQKPGQP 
               
               
                   
               
               
                 PKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSAPLTFGG 
               
               
                   
               
               
                 GTKVEIK   DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAP 
               
               
                   
               
               
                 KLLIYWASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQGT 
               
               
                   
               
               
                 KVEIK 
               
            
           
         
       
     
     Underlined bold region is amino acid linker sequence 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 50: 
                   
               
               
                 GAACTGGTGATGACCCAGAGCCCGGATAGTCTGGCAGTTAGCCTGGG 
               
               
                   
               
               
                 CGAACGCGCCACCATTAACTGCAAAAGCAGCCAGAGCGTGCTGTACAGCAGCA 
               
               
                   
               
               
                 ACAACAAGAGCTACCTGGCCTGGTATCAGCAGAAACCGGGTCAGCCTCCGAAA 
               
               
                   
               
               
                 CTGCTGATTTACTGGGCAAGCACCCGTGAAAGTGGCGTGCCGGATCGCTTTAGC 
               
               
                   
               
               
                 GGCAGCGGTAGCGGTACCGATTTCACCCTGACAATCAGCAGCCTGCAGGCCGA 
               
               
                   
               
               
                 AGATGTTGCCGTGTACTACTGCCAGCAGTACTACAGCGCCCCGTTAACCTTCGG 
               
               
                   
               
               
                 CGGTGGCACCAAAGTGGAGATTAAAACCGTGGCCGCCCCGGATATTCAGATGA 
               
               
                   
               
               
                 CCCAAAGCCCGAGTAGCCTGAGCGCAAGCGTGGGTGATCGCGTGACCTATTACC 
               
               
                   
               
               
                 TGCAAAGCCAGCCAGGACGTGACCACCGCAGTTGCCTGGTACCAGCAGAAGCC 
               
               
                   
               
               
                 GGGCAAAGCACCGAAGCTGCTGATTTATTGGGCAAGCACCCGCCATACCGGTG 
               
               
                   
               
               
                 TGCCTAGCCGTTTCAGCGGTAGTGGCAGTGGCACCGACTTTACCCTGACCATCA 
               
               
                   
               
               
                 GCAGTCTGCAGCCGGAAGACTTCGCCACCTACTATTGCCAACAGCACTACAGCA 
               
               
                   
               
               
                 CCCCGCTGACCTTTGGCCAGGGCACCAGGTGGAAATTAAG 
               
               
                   
               
               
                 Combined (SEQ ID NO: 49 and 50):  
               
               
                 gaactggtgatgacccagagcccggatagtctggcagttagcctgggcgaacgcgccacc 
               
               
                 E  L  V  M  T  Q  S  P  D  S  L  A  V  S  L  G  E  R  A  T 
               
               
                   
               
               
                 attaactgcaaaagcagccagagcgtgctgtacagcagcaacaacaagagctacctggcc 
               
               
                 I  N  C  K  S  S  Q  S  V  L  Y  S  S  N  N  K  S  Y  L  A 
               
               
                   
               
               
                 tggtatcagcagaaaccgggtcagcctccgaaactgctgatttactgggcaagcacccgt 
               
               
                 W  Y  Q  Q  K  P  G  Q  P  P  K  L  L  I  Y  W  A  S  T  R 
               
               
                   
               
               
                 gaaagtggcgtgccggatcgctttagcggcagcggtagcggtaccgatttcaccctgaca 
               
               
                 E  S  G  V  P  D  R  F  S  G  S  G  S  G  T  D  F  T  L  T 
               
               
                   
               
               
                 atcagcagcctgcaggccgaagatgttgccgtgtactactgccagcagtactacagcgcc 
               
               
                 I  S  S  L  Q  A  E  D  V  A  V  Y  Y  C  Q  Q  Y  Y  S  A 
               
               
                   
               
               
                 ccgttaaccttcggcggtggcaccaaagtggagattaaaaccgtggccgccccggatatt 
               
               
                 P  L  T  F  G  G  G  T  K  V  E  I  K  T  V  A  A  P  D  I 
               
               
                   
               
               
                 cagatgacccaaagcccgagtagcctgagcgcaagcgtgggtgatcgcgtgaccattacc 
               
               
                 Q  M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T  I  T 
               
               
                   
               
               
                 tgcaaagccagccaggacgtgaccaccgcagttgcctggtaccagcagaagccgggcaaa 
               
               
                 C  K  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P  G  K 
               
               
                   
               
               
                 gcaccgaagctgctgatttattgggcaagcacccgccataccggtgtgcctagccgtttc 
               
               
                 A  P  K  L  L  I  Y  W  A  S  T  R  H  T  G  V  P  S  R  F 
               
               
                   
               
               
                 agcggtagtggcagtggcaccgactttaccctgaccatcagcagtctgcagccggaagac 
               
               
                 S  G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P  E  D 
               
               
                   
               
               
                 ttcgccacctactattgccaacagcactacagcaccccgctgacctttggccagggcacc 
               
               
                 F  A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q  G  T 
               
               
                   
               
               
                 aaggtggaaattaag 
               
               
                 K  V  E  I  K 
               
               
                   
               
               
                 E10-13C6 HC DVD Fusion sequence - Amino Acid (SEQ ID NO: 51): 
               
               
                 MGRLTSSFLLIVPAYVLSQLTLKESGPGILKPSQTLSLTCSLSGFSLSTSG 
               
               
                   
               
               
                 VGVGWFRQPGKGLEWLALIWWDDDKYYNPSLKSQLSISKDFSRNQVFLKISNVDI 
               
               
                   
               
               
                 ADTATYYCARRDPFGYDNAMGYWGQGTSVTVSS   EVQLVESGGGLVQPG 
               
               
                   
               
               
                 GSLRLSCAASGFAFNYYDIHWVRQAPGKGLEWVAYINPGGGNTYYADSVKGRFTI 
               
               
                   
               
               
                 SADTSKNTAYLQMNSLRAEDTAVYYCARQLYGNSFMDYWGQGTLVYVSS 
               
            
           
         
       
     
     Underlined bold region is amino acid linker sequence. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 52): 
                   
               
               
                 ATGGGTCGCCTGACCAGTAGCTTTCTGCTGCTGATTGTGCCTGCCTAT 
               
               
                   
               
               
                 GTGTTAAGCCAGCTGACCCTGAAGGAGAGCGGCCCGGGTATTCTGAAACCTAG 
               
               
                   
               
               
                 CCAGACCCTGAGCCTGACCTGCAGCCTGAGCGGTTTTAGCCTGAGTACCAGCGG 
               
               
                   
               
               
                 TGTGGGCGTTGGTTGGTTCCGCCAGCCGAGCGGTAAAGGTCTGGAATGGCTGGC 
               
               
                   
               
               
                 CCTGATTTGGTGGGATGATGATAAATACTACAACCCGAGCCTGAAAAGCCAGCT 
               
               
                   
               
               
                 GAGCATTAGCAAAGATTTTAGCCGCAATCAGGTTTTCCTGAAAATCAGCAACGT 
               
               
                   
               
               
                 GGACATTGCCGACACCGCCACCTACTATTGCGCCCGCCGCGACCCGTTTGGCTA 
               
               
                   
               
               
                 TGATAACGCCATGGGCTACTGGGGCCAGGGTACCAGCGTTACCGTTAGCAGCG 
               
               
                   
               
               
                 CCAGCACCAAAGGCCCGGAAGTGCAGCTGGTTGAAAGCGGTGGTGGTCTGGTT 
               
               
                   
               
               
                 CAGCCGGGTGGTAGTCTGCGTCTGAGTTGCGCCGCCAGCGGCTTTGCCTTCAAT 
               
               
                   
               
               
                 TATTATGATATCCATTGGGTTCGCCAGGCACCGGGTAAGGGCCTGGAATGGGTG 
               
               
                   
               
               
                 GCATACATTAATCCGGGTGGCGGTAACACCTACTATGCCGACAGCGTGAAAGG 
               
               
                   
               
               
                 TCGCTTCACCATCAGCGCCGATACCAGCAAGAACACCGCCTATCTGCAGATGAA 
               
               
                   
               
               
                 CAGCCTGCGTGCCGAAGATACCGCCGTGTATTATTGTGCCCGCCAGCTGTATGG 
               
               
                   
               
               
                 CAACAGCTTCATGGATTATTGGGGCCAAGGCACCCTGGTTACCGTTAGCAGC 
               
               
                   
               
               
                 Combined (SEQ ID NOS: 51 and 52): 
               
               
                 atgggtcgcctgaccagtagctttctgctgctgattgtgcctgcctatgtgttaagccag 
               
               
                 M  G  R  L  T  S  S  F  L  L  L  I  V  P  A  Y  V  L S  Q 
               
               
                   
               
               
                 ctgaccctgaaggagagcggcccgggtattctgaaacctagccagaccctgagcctgacc 
               
               
                 L  T  L  K  E  S  G  P  G  I  L  K  P  S  Q  T  L  S  L  T 
               
               
                   
               
               
                 tgcagcctgagcggttttagcctgagtaccagcggtgtgggcgttggttggttccgccag 
               
               
                 C  S  L  S  G  F  S  L  S  T  S  G  V  G  V  G  W  F  R  Q 
               
               
                   
               
               
                 ccgagcggtaaaggtctggaatggctggccctgatttggtgggatgatgataaatactac 
               
               
                 P  S  G  K  G  L  E  W  L  A  L  I  W  W  D  D  D  K  Y  Y 
               
               
                   
               
               
                 aacccgagcctgaaaagccagctgagcattagcaaagattttagccgcaatcaggttttc 
               
               
                 N  P  S  L  K  S  Q  L  S  I  S  K  D  F  S  R  N  Q  V  F 
               
               
                   
               
               
                 ctgaaaatcagcaacgtggacattgccgacaccgccacctactattgcgcccgccgcgac 
               
               
                 L  K  I  S  N  V  D  I  A  D  T  A  T  Y  Y  C  A  R  R  D 
               
               
                   
               
               
                 ccgtttggctatgataacgccatgggctactggggccagggtaccagcgttaccgttagc 
               
               
                 P  F  G  Y  D  N  A  M  G  Y  W  G  Q  G  T  S  V  T  V  S 
               
               
                   
               
               
                 agcgccagcaccaaaggcccggaagrgcagctggttgaaagcggtggtggtctggttcag 
               
               
                 S  A  S  T  K  G  P  E  V  Q  L  V  E  S  G  G  G  L  V  Q 
               
               
                   
               
               
                 ccgggtggtagtctgcgtctgagttgcgccgccagcggctttgccttcaattattatgat 
               
               
                 P  G  G  S  L  R  L  S  C  A  A  S  G  F  A  F  N  Y  Y  D 
               
               
                   
               
               
                 atccattgggttcgccaggcaccgggtaagggcctggaatgggtggcatacattaatccg 
               
               
                 I  H  W  V  R  Q  A  P  G  K  G  L  E  W  V  A  Y  I  N  P 
               
               
                   
               
               
                 ggtggcggtaacacctactatgccgacagcgtgaaaggtcgcttcaccatcagcgccgat 
               
               
                 G  G  G  N  T  Y  Y  A  D  S  V  K  G  R  F  T  I  S  A  D 
               
               
                   
               
               
                 accagcaagaacaccgcctatctgcagatgaacagcctgcgtgccgaagataccgccgtg 
               
               
                 T  S  K  N  T  A  Y  L  Q  M  N  S  L  R  A  E  D  T  A  V 
               
               
                   
               
               
                 tattattgtgcccgccagctgtatggcaacagcttcatggattattggggccaaggcacc 
               
               
                 Y  Y  C  A  R  Q  L  Y  G  N  S  F  M  D  Y  W  G  Q  G  T 
               
               
                   
               
               
                 ctggttaccgttagcagc 
               
               
                 L  V  T  V  S  S 
               
               
                   
               
               
                 E10-13C6 LC DVD Fusion sequence - Amino Acid (SEQ ID NO: 53): 
               
               
                 MGIKMKSQTQAFVFAFLWLSGVDGDIVMTQSQKFMSTSVGDRVSLTCK 
               
               
                   
               
               
                 ASQNVGTAVAWYQQKPGQSPKLLIYSASNRYTGVPDRFTGSGSGTDFTLTISNMQS 
               
               
                   
               
               
                 EDLADYFCQQYSSYPLTFGAGTKLELRR   DIQMTQSPSSLSASVGDRVTITCR 
               
               
                   
               
               
                 ASQDVTTAVAWYQQKPGKAPKLLIYWASRLHNGVPSRFSGSGSGTDFTLTISSLQP 
               
               
                   
               
               
                 EDFATYYCQQHYSTPLTFGQGTKVEIK 
               
            
           
         
       
     
     Underlined bold region is amino acid linker sequence. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 54): 
                   
               
               
                 ATGGGCATCAAAATGAAGAGCCAGACCCAGGCCTTTGTGTTTGCCTT 
               
               
                   
               
               
                 TCTGTGGCTGAGTGGCGTGGATGGCGATATCGTGATGACCCAGAGCCAAAAGTT 
               
               
                   
               
               
                 CATGAGCACCAGCGTGGGCGATCGCGTGAGCCTGACCTGCAAAGCCAGCCAGA 
               
               
                   
               
               
                 ACGTGGGCACCGCAGTGGCATGGTACCAGCAGAAACCGGGCCAGAGCCCGAAA 
               
               
                   
               
               
                 CTGCTGATCTACAGCGCAAGCAATCGCTATACCGGTGTTCCGGATCGCTTTACA 
               
               
                   
               
               
                 GGCAGCGGCAGCGGCACCGACTTTACCCTGACCATTAGCAACATGCAGAGCGA 
               
               
                   
               
               
                 AGACCTGGCCGACTATTTTTGCCAGCAGTACAGCAGCTATCCGCTGACCTTTGG 
               
               
                   
               
               
                 CGCCGGCACCAAATTAGAACTGCGCCGTACCGTTGCCGCCCCGGATATTCAGAT 
               
               
                   
               
               
                 GACCCAAAGCCCGAGTAGCCTGAGCGCAAGCGTGGGCGACCGTGTGACCATTA 
               
               
                   
               
               
                 CCTGTCGCGCCAGCCAGGACGTTACCACCGCAGTTGCCTGGTATCAGCAAAAAC 
               
               
                   
               
               
                 CGGGCAAAGCCCCGAAGCTGCTGATCTATTGGGCAAGTCGTCTGCATAACGGC 
               
               
                   
               
               
                 GTTCCGAGCCGCTTTAGCGGCAGTGGTAGCGGCACCGATTTCACCCTGACCATC 
               
               
                   
               
               
                 ACACCGCTGACCTTCGGCCAGGGCACCAAGGTGGAAATTAAA 
               
               
                   
               
               
                 Combined (SEQ ID NOS: 53 and 54): 
               
               
                 atgggcatcaaaatgaagagccagacccaggcctttgtgtttgcctttctgtggctgagt 
               
               
                 M  G  I  K  M  K  S  Q  T  Q  A  F  V  F  A  F  L  W  L  S 
               
               
                   
               
               
                 ggcgtggatggcgatatcgtgatgacccagagccaaaagttcatgagcaccagcgtgggc 
               
               
                 G  V  D  G  D  I  V  M  T  Q  S  Q  K  F  M  S  T  S  V  G   
               
               
                   
               
               
                 gatcgcgtgagcctgacctgcaaagccagccagaacgtgggcaccgcagtggcatggtac 
               
               
                 D  R  V  S  L  T  C  K  A  S  Q  N  V  G  T  A  V  A  W  Y 
               
               
                   
               
               
                 cagcagaaaccgggccagagcccgaaactgctgatctacagcgcaagcaatcgctatacc 
               
               
                 Q  Q  K  P  G  Q  S  P  K  L  L  I  Y  S  A  S  N  R  Y  T 
               
               
                   
               
               
                 ggtgttccggatcgctttacaggcagcggcagcggcaccgactttaccctgaccattagc 
               
               
                 G  V  P  D  R  F  T  G  S  G  S  G  T  D  F  T  L  T  I  S 
               
               
                   
               
               
                 aacatgcagagcgaagacctggccgactctttttgccagcagtacagcagctatccgctg 
               
               
                 N  M  Q  S  E  D  L  A  D  Y  F  C  Q  Q  Y  S  S  Y  P  L 
               
               
                   
               
               
                 acctttggcgccggcaccaaattagaactgcgccgtaccgttgccgccccggatattcag 
               
               
                 T  F  G  A  G  T  K  L  E  L  R  R  T  V  A  A  P  D  I  Q 
               
               
                   
               
               
                 atgacccaaagcccgagtagcctgagcgcaagcgtgggcgaccgtgtgaccattacctgt 
               
               
                 M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T  I  T  C 
               
               
                   
               
               
                 cgcgccagccaggacgttaccaccgcagttgcctggtatcagcaaaaaccgggcaaagcc 
               
               
                 R  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P  G  K  A 
               
               
                   
               
               
                 ccgaagctgctgatctattgggcaagtcgtctgcataacggcgttccgagccgctttagc 
               
               
                 P  K  L  L  I  Y  W  A  S  R  L  H  N  G  V  P  S  R  F  S 
               
               
                   
               
               
                 ggcagtggtagcggcaccgatttcaccctgaccatcagcagcctgcagccggaggatttt 
               
               
                 G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P  E  D  F 
               
               
                   
               
               
                 gccacctactactgtcagcagcactacagcacaccgctgaccttcggccagggcaccaag 
               
               
                 A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q  G  T  K 
               
               
                   
               
               
                 gtggaaattaaa 
               
               
                 V  E  I  K 
               
               
                   
               
               
                 F4-13C6 HC DVD Fusion sequence - Amino Acid (SEQ ID NO: 55):  
               
               
                 MGRLTSSFLLLIVPAYYLSQLTLKBSGPGILKPSQTLSLTCSLSGFSLSTSG 
               
               
                   
               
               
                 VGVGWFRQPSGKGLEWLALIWWDDDKYYNPSLKSQLSISKDFSRNQVFLKISNVDI 
               
               
                   
               
               
                 ADTATYYCARRDPFGYDNAMGYWGQGTSVTVSS   EVQLVESGGGLVQPG 
               
               
                   
               
               
                 GSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAYIKPGGGNTYYADSVKGRFTI 
               
               
                   
               
               
                 SADTSKNTAYLQMNSLRAEDTAVYYCARQLYGNSFFDYWGQGTLVTVSS 
               
            
           
         
       
     
     Underlined bold region is amino acid linker sequence. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 56): 
                   
               
               
                 ATGGGTCGCCTGACCAGTAGCTTTCTGCTGCTGATTGTGCCTGCCTAT 
               
               
                   
               
               
                 GTGTTAAGCCAGCTGACCCTGAAGGAGAGCGGCCCGGGTATTCTGAAACCTAG 
               
               
                   
               
               
                 CCAGACCCTGAGCCTGACCTGCAGCCTGAGCGGTTTTAGCCTGAGTACCAGCGG 
               
               
                   
               
               
                 TGTGGGCGTTGGTTGGTTCCGCCAGCCGAGCGGTAAAGGTCTGGAATGGCTGGC 
               
               
                   
               
               
                 CCTGATTTGGTGGGATGATGATAAATACTACAACCCGAGCCTGAAAAGCCAGCT 
               
               
                   
               
               
                 GAGCATTAGCAAAGATTTTAGCCGCAATCAGGTTTTVVTGAAAATCAGCAACGT 
               
               
                   
               
               
                 GGACATTGCCGACACCGCCACCTACTATTGCGCCCGCCGCGACCCGTTTGGCTA 
               
               
                   
               
               
                 TGATAACGCCATGGGCTACTGGGGCCAGGGTACCAGCGTTACCGTTAGCAGCG 
               
               
                   
               
               
                 CCAGCACCAAAGGCCCGGAAGTGCAGCTGGTTGAAAGCGGTGGTGGTCTHGYT 
               
               
                   
               
               
                 CAGCCGGGTGGTAGTCTGCGTCTGAGTTGCGCCGCCAGCGGCTTTGCCTTCAAT 
               
               
                   
               
               
                 TATTATGATATGTTTTGGGTTCGCCAGGCACCGGGTAAGGGCCTGGAATGGGTG 
               
               
                   
               
               
                 GCATACATTAAACCGGGTGGCGGTAACACCTACTATGCCGACAGCGTGAAAGG 
               
               
                   
               
               
                 TCGCTTCACCATCAGCGCCGATACCAGCAAGAACACCGCCTATCTGCAGATGAA 
               
               
                   
               
               
                 CAGCCTGCGTGCCGAAGATACCGCCGTGTATTATTGTGCCCGCCAGCTGTATGG 
               
               
                   
               
               
                 CAACAGCTTCTTTGATTATTGGGGCCAAGGCACCCTGGTTACCGTTAGCAGC 
               
               
                   
               
               
                 Combined (SEQ ID NOS: 55 and 56): 
               
               
                 atgggtcgcctgaccagtagctttctgctgctgattgtgcctgcctatgtgttaagccag 
               
               
                 M  G  R  L  T  S  S  F  L  L  L  I  V  P  A  Y  V  L  S  Q 
               
               
                   
               
               
                 ctgaccctgaaggagagcggcccgggtattctgaaacctagccagaccctgagcctgacc 
               
               
                 L  T  L  K  E  S  G  P  G  I  L  K  P  S  Q  T  L  S  L  T 
               
               
                   
               
               
                 tgcagcctgagcggttttagcctgagtaccagcggtgtgggcgttggttggttccgccag 
               
               
                 C  S  L  S  G  F  S  L  S  T  S  G  V  G  V  G  W  F  R  G 
               
               
                   
               
               
                 aacccgagcctgaaaagccagctgagcattagcaaagattttagccgcaatcaggttttc 
               
               
                 P  S  G  K  G  L  E  W  L  A  L  I  W  W  D  D  D  K  Y  Y 
               
               
                   
               
               
                 ctgaaaatcagcaacgtggacattgccgacaccgccacctactattgcgcccgccgcgac 
               
               
                 N  P  S  L  K  S  Q  L  S  I  S  K  D  F  S  R  N  Q  V  F 
               
               
                   
               
               
                 ctgaaaatcagcaacgtggacattgccgacaccgccacctactattgcgcccgccgcgac 
               
               
                 L  K  I  S  N  V  D  I  A  D  T  A  T  Y  Y  C  A  R  R  D 
               
               
                   
               
               
                 ccgtttggctatgataacgccatgggctactggggccagggtaccagcgttaccgttagc 
               
               
                 P  F  G  Y  D  N  A  M  G  Y  W  G  Q  G  T  S  V  T  V  S 
               
               
                   
               
               
                 agcgccagcaccaaaggcccggaagtgcagctggttgaaagcggtggtggtctggttcag 
               
               
                 S  A  S  T  K  G  P  E  V  Q  L  V  E  S  G  G  G  L  V  Q 
               
               
                   
               
               
                 ccgggtggtagtctgcgtctgagttgcgccgccagcggctttgccttcaattattatgat 
               
               
                 P  G  G  S  L  R  L  S  C  A  A  S  G  F  A  F  N  Y  Y  D 
               
               
                   
               
               
                 atgttttgggttcgccaggcaccgggtaagggcctggaatgggtggcatacattaaaccg 
               
               
                 M  F  W  V  R  Q  A  P  G  K  G  L  E  W  V  A  Y  I  K  P 
               
               
                   
               
               
                 ggtggcggtaacacctactatgccgacagcgtgaaaggtcgcttcaccatcagcgccgat 
               
               
                 G  G  G  N  T  Y  Y  A  D  S  V  K  G  R  F  T I  S  A  D 
               
               
                   
               
               
                 accagcaagaacaccgcctatctgcagatgaacagcctgcgtgccgaagataccgccgtg 
               
               
                 T  S  K  N  T  A  Y  L  Q  M  N  S  L  R  A  E  D  T  A  V 
               
               
                   
               
               
                 tattattgtgcccgccagctgtatggcaacagcttctttgattattggggccaaggcacc 
               
               
                 Y  Y  C  A  R  Q  L  Y  G  N  S  F  F  D  Y  W  G  Q  G  T 
               
               
                   
               
               
                 ctggttaccgttagcagc 
               
               
                 L  V  T  V  S  S 
               
               
                   
               
               
                 F4-13C6 LC DVD Fusion sequence - Amino Acid (SEQ ID NO: 57): 
               
               
                 MGIKMKSQTQAFVFAFLWLSGVDGDIVMTQSQKFMSTSVGDRVSLCK 
               
               
                   
               
               
                 ASQNVGTAVAWYQQKPGQSPKLLIYSASNRYTGVPDRFTGSGSGTDFTLTISNMQS 
               
               
                   
               
               
                 EDLADYFCQQYSSYPLTFGAGTKLELRR   DIQMTQSPSSLSASVGDRVTITCK 
               
               
                   
               
               
                 ASQDVTTAVAWYQQKPGKAPKLLIYWASTRHTGVPSRFSGSGSGTDFTLTISSLQP 
               
               
                   
               
               
                 EDFATYYCQQHYSTPLTFGQGTKVEIK 
               
            
           
         
       
     
     Underlined bold region is amino acid linker sequence. 
     
       
         
           
               
               
            
               
                 Nucleotide (SEQ ID NO: 58) 
                   
               
               
                 ATGGGCATCAAAATGAAGAGCCAGACCCAGGCCTTTGTGTTTGCCTT 
               
               
                   
               
               
                 TCTGTGGCTGAGTGGCGTGGATGGCGATATCGTGATGACCCAGAGCCAAAAGTT 
               
               
                   
               
               
                 CATGAGCACCAGCGTGGGCGATCGCGTGAGCCTGACCTGCAAAGCCAGCCAGA 
               
               
                   
               
               
                 ACGTGGGCACCGCAGTGGCATGGTACCADCAGAAACCGGGCCAGAGCCCGAAA 
               
               
                   
               
               
                 CTGCTGATCTACAGCGCAAGCAATCGCTATACCGGTGTTCCGGATCGCTTTACA 
               
               
                   
               
               
                 GGCAGCGGCAGCGGCACCGACTTTACCCTGACCATTAGCAACATGCAGAGCGA 
               
               
                   
               
               
                 AGACCTGGCCGACTATTTTTGCCAGCAGTACAGCAGCTATCCGCTGACCTTTGG 
               
               
                   
               
               
                 CGCCGGCACCAAATTAGAACTGCGCCGTACCGTTGCCGCCCCGGATATTCAGAT 
               
               
                   
               
               
                 GACCCAAAGCCCGAGTAGCCTGAGCGCAAGCGTGGGCGACCGTGTGACCATTA 
               
               
                   
               
               
                 CCTGTAAAGCCAGCCAGGACGTTACCACCGCAGTTGCCTGGTATCAGCAAAAA 
               
               
                   
               
               
                 CCGGGCAAAGCCCCGAAGCTGCTGATCTATTGGGCAAGTACCCTCATACCGGC 
               
               
                   
               
               
                 GTTCCGAGCCGCTTTAGCGGCAGTGGTAGCGGCACCGATTTCACCCTGACCATC 
               
               
                   
               
               
                 AGCAGCCTGCAGCCGGAGGATTTTGCCACCTACTACTGTCAGCAGCACTACAGC 
               
               
                   
               
               
                 ACACCGCTGACCTTCGGCCAGGGCACCAAGGTGGAAATTAAA 
               
               
                   
               
               
                 Nucleotide (SEQ ID NO: 57 and 58): 
               
               
                 atgggcatcaaaatgaagagccagacccaggcctttgtgtttgcctttctgtggctgagt 
               
               
                 M  G  I  K  M  K  S  Q  Q  T  A  F  V  F  A  F  L  W  L  S 
               
               
                   
               
               
                 ggcgtggatggcgatatcgtgatgacccagagccaaaagttcatgagcaccagcgtgggc 
               
               
                 G  V  D  G  D  I  V  M  T  Q  S  Q  K  F  M  S  R  S  V  G 
               
               
                   
               
               
                 gatcgcgtgagcctgacctgcaaafccagccagaacgtgggcaccgcagtggcatggtac 
               
               
                 D  R  V  S  L  T  C  K  A  S  Q  N  V  G  T  A  V  A  W  Y 
               
               
                   
               
               
                 cagcagaaaccgggccagagcccgaaactgctgatctacagcgcaagcaatcgctatacc 
               
               
                 Q  Q  K  P  G  Q  S  P  K  L  L  I  Y  S  A  S  N  R  Y  T 
               
               
                   
               
               
                 ggtgttccggatcgctttacaggcagcggcagcggcaccgactttaccctgaccattagc 
               
               
                 G  V  P  D  R  F  T  G  S  G  S  G  T  D  F  T  L  T  I  S 
               
               
                   
               
               
                 aacatgcagagcgaagacctggccgactatttttgccagcagtacagcagctatccgctg 
               
               
                 N  M  Q  S  E  D  L  A  D  Y  F  C  Q  Q  Y  S  S  Y  P  L 
               
               
                   
               
               
                 acctttggcgccggcaccaaattagaactgcgccgtaccgttgccgccccggatattcag 
               
               
                 T  F  G  A  G  T  K  L  E  L  R  R  T  V  A  A  P  D  I  Q 
               
               
                   
               
               
                 atgacccaaagcccgagtagcctgagcgcaagcgtgggcgaccgtgtgaccattacctgt 
               
               
                 M  T  Q  S  P  S  S  L  S  A  S  V  G  D  R  V  T  I  T  C 
               
               
                   
               
               
                 aaagccagccaggacgttaccaccgcagttgcctggtatcagcaaaaaccgggcaaagcc 
               
               
                 K  A  S  Q  D  V  T  T  A  V  A  W  Y  Q  Q  K  P  G  K  A 
               
               
                   
               
               
                 ccgaagctgctgatctattgggcaagtacccgtcataccggcgttccgagccgctttagc 
               
               
                 P  K  L  L  I  Y  W  A  S  T  R  H  T  G  V  P  S  R  F  S 
               
               
                   
               
               
                 ggcagtggtagcggcaccgatttcaccctgaccatcagcagcctgcagccggaggatttt 
               
               
                 G  S  G  S  G  T  D  F  T  L  T  I  S  S  L  Q  P  E  D  F 
               
               
                   
               
               
                 gccacctactactgtcagcagcactacagcacaccgctgaccttcggccagggcaccaag 
               
               
                 A  T  Y  Y  C  Q  Q  H  Y  S  T  P  L  T  F  G  Q  G  T  K 
               
               
                   
               
               
                 gtggaaattaaa 
               
               
                 V  E  I  K 
               
            
           
         
       
     
     In an embodiment of any of the antibodies and/or scFv described herein (of the compositions described herein), the antibody and/or scFv is a neutralizing antibody/scFv with respect to the relevant Ebola virus. 
     In an embodiment, the antibody or scFv binds the relevant Ebola virus glycoprotein pre-fusion core, which is a heterohexamer of three copies of the GP1 and 3 copies of the GP2. 
     In an embodiment, the antibody comprises an Fc region having a sequence identical to a human Fc region. 
     In an embodiment, the Fc region of the antibody is glycosylated. 
     A “humanized” antibody as used herein, unless otherwise indicated, is a chimeric antibody that contains minimal sequence (CDRs) derived from non-human immunoglobulin (e.g. such as a mouse immunoglobulin). In one embodiment, a humanized antibody is an antibody having a sequence of a human immunoglobulin (recipient antibody) in which CDR residues of a hypervariable region (HVR) of the recipient are replaced by CDR residues from a non-human species (donor antibody) such as a mouse having the desired specificity. In some instances, FR residues of the human immunoglobulin variable domain are replaced by corresponding non-human residues, for example by a back-mutation. In general, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin, and all or substantially all of the FRs are those of a human immunoglobulin sequence. The humanized antibody optionally will also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. See, e.g., Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); Presta, Curr. Op. Struct. Biol. 2:593-5% (1992), Vaswani and Hamilton, Ann. Allergy, Asthma &amp; Immunol. 1:105-115 (1998); Harris, Biochem. Soc. Transactions 23:1035-1038 (1995); Hurle and Gross, Curr. Op. Biotech. 5:428-433 (1994); and U.S. Pat. Nos. 6,982,321 and 7,087,409, the contents of each of which references and patents are hereby incorporated by reference in their entirety. Other techniques to humanize a monoclonal antibody are described in U.S. Pat. Nos. 4,816,567; 5,807,715; 5,866,692; 6,331,415; 5,530,101; 5,693,761; 5,693,762; 5,585,089; and 6,180,370, the content of each of which is hereby incorporated by reference in its entirety. The framework regions of the antibodies of the invention having a sequence identical to a human framework region may include amino acid residues not encoded by human germline sequences (e.g., mutations introduced by random or site-specific mutagenesis). In an embodiment, the isolated antibody or antigen-binding antibody fragment comprises a variable domain framework sequence having a sequence identical to a human variable domain framework sequence FR1, FR2, FR3 or FR4. In an embodiment, the isolated antibody or antigen-binding antibody fragment comprises a variable domain framework sequence having a sequence identical to at least two of human variable domain framework sequences FR1, FR2, FR3 or FR4. In an embodiment, the isolated antibody or antigen-binding antibody fragment comprises a variable domain framework sequence having a sequence identical to at least three of human variable domain framework sequences FR1, FR2, FR3 or FR4. In an embodiment, the isolated antibody or antigen-binding antibody fragment comprises a variable domain framework sequence having a sequence identical to all four of human variable domain framework sequences FR1, FR2, FR3 and FR4. 
     The term “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain, including native sequence Fc regions and variant Fc regions. Although the boundaries of the Fc region of an immunoglobulin heavy chain might vary, the human IgG heavy chain Fc region is often defined to stretch from an amino acid residue at position Cys226, or from Pro230, to the carboxyl-terminus thereof. The C-terminal lysine of the Fc region may be removed, for example, during production or purification of the antibody, or by recombinantly engineering the nucleic acid encoding a heavy chain of the antibody. Accordingly, an intact antibody as used herein may be an antibody with or without the otherwise C-terminal lysine. 
     In an embodiment, the antibodies of the invention described herein comprise a human Fc region or a variant human Fc region. A variant human Fc region comprises an amino acid sequence which differs from that of a native sequence Fc region by virtue of at least one amino acid modification, yet retains at least one effector function of the native sequence human Fc region. Preferably, the variant Fc region has at least one amino acid substitution compared to a native sequence Fc region or to the Fc region of a parent polypeptide, e.g. from about one to about ten amino acid substitutions, and preferably, from about one to about five amino acid substitutions in a native sequence Fc region or in the Fc region of the parent polypeptide. The variant Fc region herein will preferably possess at least about 80% sequence identity with a native sequence Fc region and/or with an Fc region of a parent polypeptide, and most preferably, at least about 90% sequence identity therewith, more preferably, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% sequence identity therewith. 
     In an embodiment, the scFv is a variable domain light chain (VL) and a variable domain heavy chain (VH) which are linked N—C or C—N, respectively, via a peptide linker. In an embodiment the linker of the scFv is 5-30 amino acids in length in an embodiment the linker of the scFv is 10-25 amino acids in length. In an embodiment the peptide linker comprises glycine, serine and/or threonine residues. For example, see Bird et al., Science, 242: 423-426 (1988) and Huston et al., Proc Natl. Acad. Sci. USA, 85:5879-5883 (1988), each of which are hereby incorporated by reference in their entirety. 
     In an embodiment, the antibody and or scFv(s) of the composition of the invention do not recognize an Ebola GP1 mucin-like domain. In an embodiment, the antibody and or scFv(s) of the composition of the invention do not recognize an Ebola GP1 variable glycan cap. 
     For trispecific constructs, which target three different Filovirus strains and/or species, an IgG directed at the prefusion glycoprotein core for one strain is fused two different scFvs (each directed at a prefusion glycoprotein core for two other strains, respectively). The scFvs are fused to the IgG at two different positions, with the two scFv having specificity for the different viruses. In a non-limiting example, an SUDV-specific IgG with EBOV-specific scFv as light chain N-terminal fusion and a MARV-specific scFv as a heavy chain C-terminal fusion. 
     The phrase “and/or” as used herein, with option A and/or option B for example, encompasses the embodiments of (i) option A, (ii) option B, and (iii) option A plus option B. 
     It is understood that wherever embodiments are described herein with the language “comprising,” otherwise analogous embodiments described in terms of “consisting of” and/or “consisting essentially of” are also provided. 
     Where aspects or embodiments of the invention are described in terms of a Markush group or other grouping of alternatives, the present invention encompasses not only the entire group listed as a whole, but each member of the group subjectly and all possible subgroups of the main group, but also the main group absent one or more of the group members. The present invention also envisages the explicit exclusion of one or more of any of the group members in the claimed invention. 
     All combinations of the various elements described herein are within the scope of the invention unless otherwise indicated herein or otherwise clearly contradicted by context. 
     This invention will be better understood from the Experimental Details, which follow. However, one skilled in the art will readily appreciate that the specific methods and results discussed are merely illustrative of the invention as described more fully in the claims that follow thereafter. 
     EXPERIMENTAL DETAILS 
     Introduction 
     Ebola virus pathogenesis and cell entry: The infectious agents Ebola virus and Marburg virus (MARV) are the two major species of the Filoviridae family of enveloped negative-sense RNA viruses (1-4). Based on nucleotide sequence and outbreak location, isolates of Ebola virus are classified into five species&#39; Zaire (EBOV), Tai Forest (TAFV), Sudan (SUDV), Reston (RESTV), and Bundibugyo (BDBV). There are two MARV variants (Marburg and Ravn). Severe human disease and deaths (30-90% case fatality rates in large outbreaks) are associated with EBOV, SUDV, BDBV, and MARV (2). Although the ecology of these agents remains incompletely understood, several species of African fruit bats appear to be reservoirs for Ebola virus and MARV (5). EBOV and SUDV are the most pathogenic among the ebolaviruses, and both have been associated with recurring outbreaks (6). Among the 13 documented EBOV outbreaks and the six SUDV outbreaks from 1976-2012, the average human case fatality rates are 70% and 52%, respectively. Together, EBOV and SUDV account for over 95% of Ebola virus-related deaths (6); these statistics do not include the ongoing EBOV outbreak in West Africa that is of unprecedented scope and geographic distribution. Therefore, a therapeutic agent that is effective against both EBOV and SUDV would greatly reduce the threat of an Ebola virus pandemic. 
     All human outbreaks occur as a result of direct contact with infected wildlife, with subsequent person-to-person transmission, mostly through the mucosa or contaminated needles. Uncontrolled viral replication is central to filovirus-induced disease, both because it is cytopathic and because it induces dysregulation of the host immune system (2, 7, 8). Therefore, antiviral therapies that reduce viral load are expected to increase patient survival, in part, by allowing time to mount an effective immune response. While many cell types can be infected with filovirus in vitro and in vivo, antigen-presenting cells (macrophages and dendritic cells) appear to be early and sustained targets of infection in vivo. Infected macrophages are unable to stimulate a robust immune response, and cause a “cytokine storm” that is proposed to be the primary cause of the blood dotting abnormalities and vascular leakage characteristic of filovirus hemorrhagic fever (9). Damage to other tissues (e.g., liver, kidneys, vascular endothelia) is thought to contribute to the above and to late-stage multi-organ failure. Death typically occurs 8-15 days after infection (10). Because of their high mortality rate, rapid proliferation, and potential for aerosolization, Ebola virus and Marburg virus are classified as Category A biodefense pathogens. There are currently no FDA-approved treatments for these infections. 
     The filovirus genome is a ˜19 kb single-strand negative-sense RNA genome that encodes seven genes arranged in a linear fashion (1-4). In mature viral particles and infected cells, the genome is intimately associated with four viral proteins; the nucleocapsid protein NP, the polymerase L, the polymerase accessory protein VP35, and the transcriptional activator protein VP30. This nucleocapsid structure is in turn encapsidated in a viral matrix, comprising proteins VP40 and VP24. The host-derived viral membrane bilayer surrounds, and is peripherally associated with, the matrix. Embedded in the viral membrane are trimers of the viral glycoprotein, GP, which mediates the first step in infection: delivery of the viral nucleocapsid “payload” into the cytoplasm of the host cell. GP is the target of virus-directed antibodies that neutralize extracellular filovirus particles (4, 11-14). 
     The mature filovirus GP spike is a trimer of three disulfide-linked GP1-GP2 heterodimers, generated by endoproteolytic cleavage of the GP0 precursor polypeptide by furin during virus assembly (4, 13-15). GP1 mediates viral adhesion to host cells and regulates the activity of the transmembrane subunit GP2, which mediates fusion of viral and cellular membranes during cell entry. The prefusion GP1-GP2 spike has a “chalice-and-bowl” morphology—the three GP2 subunits form the chalice within which the bowl, comprised of the three GP1 subunits, rests ( FIG. 1A ) (13-15), This trimeric assembly is stabilized mainly by GP1-GP2 and GP2-GP2 contacts. The GP1 subunit is organized into three subdomains. The base (‘b’, light blue) interacts extensively with GP2 and clamps it in its prefusion conformation. The head (‘h’, green) contains a putative receptor-binding sequence. Together with GP2, the base and head subdomains of GP1 form the conserved structural core of the GP1-GP2 spike. In contrast to the GP1-GP2 core, the most external subdomains of GP1—the glycan cap (‘gc’, dark blue) and the mucin-like domain (not shown) are extensively glycosylated and display a high degree of sequence variation among filovirus isolates. Therefore, antibodies with broadly cross-neutralizing activity must recognize the conserved GP1-GP2 core and not the variable glycan cap or mucin-like domain. In response to a fusion trigger within host cell endosomes, GP2 disengages from GP1 and undergoes a series of large-scale conformational changes that drive coalescence of viral and cellular membrane bilayers ( FIG. 1B ) (4, 16-19). The result of viral membrane fusion is cytoplasmic release of the viral nucleocapsid. KZ52 and 16F6 likely function by inhibiting these fusion-associated conformational changes (4, 13, 14). 
     Immunotherapy is a tractable approach to filovirus treatment pre- and post-exposure. Until recently, it has been unclear if passive immunotherapy would be effective for treatment or prophylaxis of filovirus infection (20). However, recent studies using non-human primate (NHP) models have provided convincing evidence that immunotherapy can and should be pursued (21, 22). Dr. Dye&#39;s laboratory reported that rhesus macaques can be protected up to 48 hours post-exposure from EBOV or MARV infection by passive transfer of fractionated EBOV- or MARV-specific IgG isolated from convalescent animals (same species) (21). In this study, two of the three NHPs that were challenged with EBOV, and then administered serum IgG, had no clinical signs of illness; the third developed mild, delayed signs of the disease but fully recovered ( FIG. 2 ). The control animal died eight days post exposure, as is typical for untreated infection. Similar results were obtained with MARV-challenged animals, suggesting that filovirus infection in general can be treated with antibodies. This protection required only three total administrations of the serum IgG (48 hours post exposure, then again at four and eight days). Therefore, antibody-based filovirus therapy is feasible, protective, and can be administered post-exposure. In 2012, three groups (Kobinger, Zeitlin/Olinger and Takada/Feldmann) independently reported that cocktails of mAbs could protect NHPs against EBOV challenge (22-24). The Kobinger study involved a cocktail of three GP-specific murine monoclonal antibodies (mAbs) that were administered at intervals of 3 days beginning 24 or 48 hours post-exposure. Initiation of the treatment at 24 hours conferred complete survival (414 macaques) and initiation of treatment 48 hours post-exposure conferred partial protection (2/4 macaques fully recovered) (22), The Olinger/Zeitlin study demonstrated that a cocktail of three mouse/human chimeric mAbs (known as ‘MB-003’) produced in whole plant cells provided full protection when administered 1 hour post-exposure, and partial protection when administered 24 or 48 hours post-exposure (23). The Takada/Feldmann study demonstrated that a combination of two human-mouse chimeric mAbs could partially protect NHPs against EBOV challenge (24). Three NHPs were administered a cocktail of the two mAbs 24 hours preceding challenge with EBOV, then again 24- and 48-hours post-exposure. One of the three animals survived, one had delayed onset of hemorrhagic fever and was ultimately euthanized, and the other was similar to the control. It was concluded that the protection could be improved if serum half-life of the mAbs were optimized, or if the mAbs were used in combination with other mAbs or therapies. Enhanced neutralization potency would also likely improve protection. More recent studies have shown that an optimized cocktail of three monoclonal antibodies (ZMapp) can provide protection in non-human primates up to six days post-exposure. 
     There is a gap in treatment of filovirus infection. Only a handful of animal challenge studies have been performed with mAb therapies, in part because few mAbs that target GP (the primary neutralization target) exist. Most antibodies elicited in natural infection react preferentially with a secreted, dimeric version of the glycoprotein known as sGP and do not neutralize the fusion-relevant GP spike (4, 25, 26). Wilson et al. first demonstrated that GP-specific neutralizing antibodies (nAbs) could protect mice from EBOV challenge (27). However, three of five protective antibodies recognize highly variable sequences within the GP1 mucin-like domain, rendering them unlikely candidates for development of cross-neutralizing mAbs. Antibodies KZ52 and 16F6 are among the few well-characterized nAbs and both bind to the GP prefusion core (13, 14). KZ52 was identified by phage-based panning of a B-cell antibody library isolated from a human survivor of EBOV infection (28). Initial experiments in rodent protection studies were promising, but KZ52 failed to protect in macaques when administered on days −1 and +4 at 50 mg/kg (12, 20). 16F6, a mouse mAb, was identified recently by Dr. Dye&#39;s group by vaccination with vector-based vaccine expressing SUDV GP (14). 
     mAb 16F6 is much more potent than is KZ52 against the corresponding virus species, but its murine scaffold limits therapeutic utility at this point. Fully humanized 16F6 variants have been developed (U.S. patent application Ser. No. 14/291,608, filed May 30, 2014, hereby incorporated by reference). Head-to-head comparison in neutralization assays using a vesicular stomatitis virus pseudotyped with GP (VSV-GP) with KZ52 (against EBOV GP, GPEBOV) and 16F6 (against SUDV GP, GPSUDV) indicates that 16F6 can reduce infectivity by ˜100-fold more than KZ52 at high antibody concentrations ( FIG. 3 ). Both KZ52 and 16F6 are narrowly strain specific (KZ52 for EBOV and 16F6 for SUDV), and therefore have limited potential as immunotherapeutics because they cannot cross-neutralize (13, 14). 
     Several candidate therapies and vaccines are under exploration for filovirus infection (27-33). Multiple promising vaccine candidates are able to protect NHPs from lethal challenge, including adenovirus-vectored. VSV-vectored, and virus-like particle-based vaccines (29-32). While any safe and effective EBOV vaccine will be useful for populations or workers that are at high risk for exposure, it is unlikely that vaccination against EBOV will be practical on a general population level. Therefore, there is still a need for an EBOV therapy that can be used to treat acute exposure or infection. Other biologics are under evaluation, including an antisense therapy undergoing clinical trials, and a promising RNAi therapy (33, 34). However, the use of nucleic acids as therapeutic agents in general is in its infancy and therefore there is a high barrier to FDA approval for such biologics. Furthermore, these therapeutic nucleic acids are strain-specific. Some small molecules against EBOV or host targets are also being explored, but studies are largely limited to early proof-of-concept stage (35-37). 
     Based on favorable expression and stability profiles, Bis-mAbs scKZ52-F4 LCN, scKZ52-F4 HCC, scKZ52-E10 LCN, and scKZ52-E10 HCC were chosen for additional analysis. These four Bis-mAbs showed dose-dependent neutralization of both VSV-GP pseudotyped viruses, although the IC 50  values were in general higher for VSV-GP SUDV  than VSV-GP EBOV  for the “LCN” constructs ( FIG. 9A ). For both “HCC” constructs the relative IC 50  values for the two pseudotyped viruses were approximately the same. In all cases, the highest levels (≥95%) of neutralization were achieved at 100 nM Bis-mAb concentration against both pseudotyped viruses. The four Bis-mAbs were also tested for their capacity to neutralize authentic EBOV (Kikwit-1995) and SUDV (Boniface-2000) under BioSafety Level 4 (BSL4) conditions using a plaque reduction neutralization test (PRNT) ( FIG. 98 ). For all Bis-mAbs, potent neutralization of both EBOV and SUDV were observed in both assays, with low- or sub-nanomolar IC 50  values in the PRNT assay for both viruses. 
     In Vivo Efficacy. To explore the protective potential of a single cross-binding monoclonal antibody reagent, scKZ52-F4 LCN and scKZ52-F4 HCC were evaluated for their ability to confer protection of mice in two separate mouse models with post-exposure dosing ( FIG. 10 ). For EBOV, a well-established mouse challenge model was employed with mouse-adapted (ma) EBOV (Mayinga) and WT C57BL/6 mice (40). For SUDV, this laboratory has previously reported a model for pathogenicity that utilizes type 1 interferon α/β receptor knockout mice infected at 4 weeks old with human lethal SUDV (Boniface) (41, 39). For maEBOV, a single Bis-mAb dose (200 μg) was provided 24 hours post-challenge and for SUDV, two doses (500 μg each) were provided at one and four days post-exposure. The SUDV model, which involves immunocompromised mice infected at 4 weeks of age, provides a more stringent requirement for protection, and thus higher antibody doses are required than that used for the maEBOV model. Mono-specific mAbs Z.6D8 (EBOV) and F4 (SUDV) were included as controls as they have previously shown excellent protection against their respective viruses (41). 
     Both Bis-mAb treatments resulted in high (&gt;70%) protection in both models, with scKZ52-F4 HCC conferring 100% protection against both viruses. As expected, Z.6D8 as a treatment was not protective against SUDV but was 100% protective against EBOV. SUDV monospecific mAb F4 provided 100% protection against SUDV, as we have previously reported (41) and afforded partial (30%) protection against maEBOV. However, the level of protection for F4 against maEBOV is not statistically distinguishable from a PBS control group, in which all mice succumbed to disease by day 7 (p=0.13). Murine 16F6 afforded no protection against maEBOV in a group size of n=5 challenge experiment. The 100% protection from maEBOV observed for scKZ52-F4 HCC was statistically distinguishable from both PBS and F4 controls in this experiment, whereas 70% protection of scKZ52-F4 LCN was distinguishable only from the PBS. These results indicate that both scKZ52-F4 HCC and scKZ52-F4 LCN provide statistically significant protection relative to a PBS control group. For SUDV, both Bis-mAbs and F4 were significantly protective relative to the Z.6D8 negative control treatment group. 
     Aggregate weight loss was observed in the Bis-mAb- and F4-treated group during the course of the SUDV challenge, a phenomenon we have previously reported for post-exposure dosing of protective SUDV mAbs (41,39). However, the surviving Bis-mAb or mAb-treated population continued to gain weight (on average) after day 8. For maEBOV, mean weight loss was observed during the initial infection period for scKZ52-F4 LCN- and F4-treated mice, as some mice became sick, but this trend was not observed with either Z.6D8 or scKZ52-F4 HCC mice. All mice from the Z.6D8- and scKZ52-F4 HCC-treated groups survived the infection. 
     To examine the capacity for memory immunity in Bis-mAb and mAb-treated mice, the surviving cohort of both EBOV and SUDV challenges were subjected to rechallenge (with the same isolate of virus) without mAb treatment 35 days after the initial challenge ( FIGS. 10C and 10D ). For both EBOV and SUDV, Bis-mAb or mAb treated mice were completely protected against viral rechallenge with no observable aggregate weightloss, indicating memory immunity had been established. In both cases, an untreated negative control group was also included to confirm lethality of the virus. 
     Materials and Methods 
     Bispecific construct cloning using pMAZ-IgH and pMAZ-IgL vectors from Mazor et al. (38): 
     Constructs: KZ52 scFv was linked via a flexible peptide linker to either full length E10 or F4 IgG at the N- or C-terminus of the heavy chain (HC) and light chain (LC) (total of 8 constructs) were ordered from Genewiz, South Plainfield, N.J. The nucleotide sequence was optimized for  E. coli . The constructs were re-suspended in MiliQ™ water to a final concentration of 100 ng/μL. 
     Cloning: KZ52-E10 and KZ52-F4 N-terminal HC fusions: pMAZ-IgH and the constructs were digested using BssHII and NheI in a final volume of 50 μL for 3 hours. Digests were purified using the Qiagen Gel Extraction Kit. The antibody inserts were ligated into the digested IgH vector using the Quick Ligase kit from NEB. The ligation product was then transformed into Top10 cells and plated onto LB/Carb plates. Sequences were verified via Sanger Sequencing by Genewiz. 
     KZS2-E10 and KZ52-F4 N-terminal LC fusions: pMAZ-IgL and the constructs were digested using BssHII and BsiW1 in a final volume of 50 μL for 3 hours. Subsequent steps were performed as above. 
     KZ52-F4 C-terminal HC and LC fusions: pMAZ-IgH, pMAZ-IgL and the constructs were digested with BssHII and XbaI in a final volume of 50 μL for 3 hours. Subsequent steps were performed as above. 
     KZ52-E10 C-terminal HC and LC fusions: A BamHI restriction site was engineered into the flexible peptide linker for the KZ52-F4 C-terminal IC and LC fusions. To produce KZ52-E10 C-terminal HC and LC fusions, the F4-KZ52 C-terminal HC and LC (in pMAZ vectors) were digested with BssHII and BamHI in a final volume of 50 μL for 3 hours. Subsequent steps were performed as above. 
     After sequences were verified, all 8 constructs were maxiprepped using the Macherey-Nagel maxiprep kit. Additionally, the wildtype (WT) E10 and F4 IgH and IgL DNA was also maxiprepped. 
     Transfections: Transfections were carried out at the AECOM protein production facility using HEK293F cells in 600 mL cultures as follows: 
     For each bispecific construct, the WT E10 or F4 IgH or IgL was paired with the corresponding bispecific DNA (example: E10-KZ52 N-terminal HC-IgH is paired with the E10 IgL WT). Both plasmids were co-transfected into 293F cells at a final amount of 201 μg using 1.2 mg of PEI transfection reagent in 50 mL PBS. Cells were incubated for 6 days at 37° C., 5% CO 2 , and 110 rpm. 
     Antibody purification: Cells were spun down at 4000 rpm, 4° C., for 15 minutes. The supernatant was brought to a pH of 8.0 using diluted NaOH. Protein A agarose beads (ThermoScientific) were washed in 10 mL Gentle Antibody Binding Buffer (ThermoScientific). Washed beads were then incubated with antibody containing supernatants for approximately 2 hours at 4° C. The flow through was collected. Beads were washed 2 times with 10 mL of Gentle Antibody Binding Buffer. Antibodies were eluted 5 times using 2.5 mL of Gentle Antibody Elution Buffer (ThermoScientific). Elutions were subsequently desalted into 150 mM HEPES/200 mM NaCl using PD-10 Desalting Columns (GE Healthcare). For verification of purity, SDS-PAGE (10-15%) were run and stained with Coomassie Blue dye. 
     Results 
     Multi-specific antibody-based structures are disclosed herein, including the exemplified bispecific antibodies (Bis-mAbs) comprising a genetic fusion of a single chain Fv (scFv) and an IgG, each harboring two separate specificities. In one embodiment, EBOV/SUDV Bis-mAbs were created by fusing the scFv of EBOV-specific mAb KZS2 and the IgG of SUDV specific mAbs E10 or F4. Several formats for the fusion are available, with the scFv as an N-terminal fusion to the IgG heavy chain (N′ heavy chain or HCN′), the IgG light chain (N′ light chain or LCN′); or as a C-terminal fusion to the IgG heavy and light chains (C′ heavy chain or HCC′, and C′ light chain or LCC′) (see  FIG. 4 ). KZ52 (EBOV-specific) is a human antibody, and E10 and F4 (SUDV-specific) are fully humanized versions of the mouse antibody 16F6 recently reported. All together, a total of eight Bis-mAbs were produced, and could be purified from HEK293F cells in varying yield and stability (see  FIG. 5 ). The binding of all eight for the envelope glycoprotein (GP) from EBOV or SUDV was demonstrated (see  FIGS. 5 and 7 ). 
     Finally, in a pseudotyped virus infection model, where vesicular stomatitis virus displaying the EBOV or SUDV GP was used as the infecting virus, it was found that all eight Bis-mAbs could neutralize GP-mediated cell entry for both EBOV and SUDV GP at 133 nM (see  FIG. 8 ), Testing of the bispecific antibody compositions under BSL4 conditions is performed against authentic pathogens. 
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