Human Anti-SARS-COV-2 spike (s) antibodies

Abstract

The present invention includes a monoclonal antibody or antigen-binding fragment thereof, methods of using, detection, recombinant vectors, host cells, kits, variants, and pharmaceutical compositions that include the antibody or antigen-binding fragment thereof that binds to the S2 domain of the SARS-CoV-2 Spike protein.

Description

HUMAN ANTI-SARS-COV-2 SPIKE (S) ANTIBODIESTECHNICAL FIELD OF THE INVENTION

[0001] The present invention relates in general to the field of antibodies against coronavirus, and more particularly, to human antibodies targeting the S2 domain of the Spike protein of SARS CoV-2.STATEMENT OF FEDERALLY-FUNDED RESEARCH

[0002] Not applicable.INCORPORATION-BY-REFERENCE OF MATERIALS FILED ON COMPACT DISC

[0003] The application contains a Sequence Listing which has been submitted electronically in .XML format and is hereby incorporated by reference in its entirety. Said .XML copy, created on September 20, 2024, is named “LJII_2024WO.xml” and is 657,282 bytes in size. The sequence listing contained in this .XML file is part of the specification and is hereby incorporated by reference herein in its entirety.BACKGROUND OF THE INVENTION

[0004] Without limiting the scope of the invention, its background is described in connection with SARS- CoV-2.

[0005] The worldwide spread of SARS-CoV-2 in the human population resulted in the ongoing COVID- 19 pandemic that has already caused more than 415 million infections and more than 5.8 million deaths. To initiate infection, the SARS-CoV-2 spike (S) glycoprotein promotes binding to ACE2 located on the surface of the host cell, initiating a cascade of conformational changes in the protein that drives from a metastable pre -fusion conformation to a stable post-fusion conformation. That reorganization of the protein exposes the fusion peptide and a fusion between the viral and host membranes is driven by the S2 chain of the proprotein. Given its external location on the virus and its functionality, SARS-CoV-2 spike ‘S’ protein in its pre -fusion state is one target of neutralizing antibodies and therefore the main target of the design of safe and effective therapies.SUMMARY OF THE INVENTION

[0006] As embodied and broadly described herein, an aspect of the present disclosure relates to a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191,192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261,262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331,332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401,402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471,472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; andlight chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198;206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268;276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338;346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408;416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478;486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively. In another aspect, the antibody heavy chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524. In another aspect, the antibody light chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529. In another aspect, the antigenbinding fragment is a recombinant single-chain fragment variable (scFV) antibody, Fab fragment, F(ab’)2 fragment, or Fv fragment. In another aspect, the e antibody or antigen-binding fragment is chimeric, humanized, fully human, bispecific, or multimeric. In another aspect, the antibody or antigen-binding fragment comprises an Fc portion mutated to at least one of: eliminate or enhance Fc Receptor (FcR) interactions to change a half-life, increase or decrease antibody-dependent cellular cytotoxicity, or increase or decrease complement activation. In another aspect, the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365, 375, 385, 395, 405, 415, 425, 435, 445, 455, 465, 475, 485, 495, 505, 515, or 525. In another aspect, the antibody light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, or 530. In another aspect, the antibody or antigen-binding fragment is adapted for administration or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen-binding fragment. In another aspect, the monoclonal antibody further comprises a peptide linker in a hinge region between the variable and constant domains of the heavy chain.

[0007] As embodied and broadly described herein, an aspect of the present disclosure relates to a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a monoclonal antibody or antigen-binding fragment thereof comprising a heavy chaincomplementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181,182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251,252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321,322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391,392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461,462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and a light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187,188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257,258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327,328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397,398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467,468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively. In one aspect, the antibody or antigen-binding fragment that binds to an S2 domain of SARS CoV-2 Spike protein. In another aspect, the antibody heavy chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524. In another aspect, the antibody light chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529. In another aspect, the antigen-binding fragment is a recombinant single-chain fragment variable (scFV) antibody, Fab fragment, F(ab’)2 fragment, or Fv fragment. In another aspect, the antibody or antigenbinding fragment is chimeric, humanized, fully human, bispecific, or multimeric. In another aspect, the antibody or antigen-binding fragment comprises an Fc portion mutated to at least one of: eliminate or enhance Fc Receptor (FcR) interactions to change a half-life, increase or decrease antibody-dependent cellular cytotoxicity, or increase or decrease complement activation. In another aspect, the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365, 375, 385, 395, 405, 415, 425, 435, 445, 455, 465, 475, 485, 495, 505, 515, or 525. In another aspect, the light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 10, 20, 30, 40, 50, 60,70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, or 530. In another aspect, the antibody or binding fragment thereof of further comprising a peptide linker in a hinge region between the variable and constant domains of the heavy chain. In another aspect, the antibody or antigen-binding fragment is adapted for administration or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen-binding fragment. In another aspect, the antibody or antigen-binding fragment is formulated for nasal, pulmonary, alveolar, intravenous, administration.

[0008] As embodied and broadly described herein, an aspect of the present disclosure relates to a method of treating SARS-CoV-2 in a subject in need thereof, the method comprising administering to the subject a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191,192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261,262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331,332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401,402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471,472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198;206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268;276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338;346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408;416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478;486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively. In one aspect, the antibody or antigen-binding fragment binds to an S2 domain of SARS CoV-2 Spike protein. In another aspect, the antibody heavy chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524. In another aspect, the antibody light chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529. In another aspect, the antigenbinding fragment is a recombinant single-chain fragment variable (scFV) antibody, Fab fragment, F(ab’)2fragment, or Fv fragment. In another aspect, the antibody or antigen-binding fragment is chimeric, humanized, fully human, bispecific, or multimeric. In another aspect, the antibody or antigen-binding fragment comprises an Fc portion mutated to at least one of: eliminate or enhance Fc Receptor (FcR) interactions to change a half-life, increase or decrease antibody-dependent cellular cytotoxicity, or increase or decrease complement activation. In another aspect, the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365, 375, 385, 395, 405, 415, 425, 435, 445, 455, 465, 475, 485, 495, 505, 515, or 525. In another aspect, the antibody light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, or 530. In another aspect, the antibody or antigen-binding fragment is adapted for administration or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen-binding fragment.

[0009] As embodied and broadly described herein, an aspect of the present disclosure relates to a pharmaceutical device suitable for nasal or pulmonary delivery of monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221,222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291,292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361,362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431,432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501,502, 503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236,237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306,307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376,377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446,447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516,517, 518; or 526, 527, 528, respectively, selected from an inhaler for liquids, a nebulizer, metered-dose inhaler, aerosol, and a dry powder inhaler. In one aspect, the antibody or antigen-binding fragment that binds to an S2 domain of SARS CoV-2 Spike protein.

[0010] As embodied and broadly described herein, an aspect of the present disclosure relates to a method for detecting a Spike protein of SARS-CoV-2 (SARS2-S) comprising: obtaining or having obtained abiological sample suspected of comprising a SARS-CoV-2 virus; contacting the biological sample with a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191,192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261,262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331,332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401,402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471,472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198;206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268;276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338;346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408;416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478;486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively, wherein the antibody or antigen-binding fragment that binds to an S2 domain of SARS CoV-2 Spike protein with a light chain of SEQ ID NO: 9; and detecting binding of the antibody or antigen-binding fragment to the SARS-CoV-2 virus. In one aspect, the method further comprises the step of detecting the antibody or antigen-binding fragment is diagnostic for the detection of SARS-CoV-2 in the biological sample. In one aspect, the method further comprises detecting SARS-CoV-2 by performing an immunoassay on the biological sample from a subject; wherein the immunoassay uses an antibody or antigen-binding fragment comprising the monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181,182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251,252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321,322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391,392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461,462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118;126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188;196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258;266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328;336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively. In another aspect, the immunoassay is selected from radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), sandwich assays, Western blot, immunoprecipitation, immunohistochemistry, immunofluorescence, antibody microarray, dot blotting, and fluorescence-activated cell sorting (FACS).

[0011] As embodied and broadly described herein, an aspect of the present disclosure relates to a kit for detection of a Spike protein of SARS-CoV-2 (SARS2-S) comprising a monoclonal antibody or antigenbinding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212,213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282,283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352,353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422,423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492,493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227,228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297,298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367,368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437,438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507,508; 516, 517, 518; or 526, 527, 528, respectively, for isolation and / or detection of SARS-CoV-2 in one or more sample types of human or nonhuman origin, including: blood, plasma, serum, saliva, tears, cerebrospinal fluid, lymph, urine, feces, exhaled breath condensate, perspiration, amniotic fluid, exosomes, cell and tissue lysates.

[0012] As embodied and broadly described herein, an aspect of the present disclosure relates to a recombinant nucleic acid molecule encoding an antibody or antigen-binding fragment thereof encoding a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 11, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191,192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261,262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331,332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401,402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471,472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198;206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268;276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338;346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408;416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478;486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively. In one aspect, the nucleic acid encoding the antigen-binding fragment thereof, wherein the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524. In one aspect, the nucleic acid encoding the antigen-binding fragment thereof, wherein the antibody heavy chain variable region and light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529.

[0013] As embodied and broadly described herein, an aspect of the present disclosure relates to a recombinant expression vector comprising an expression control sequence operatively linked to the recombinant nucleic acid molecule encoding a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2 and 3; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 4, 5, and 6, respectively.

[0014] As embodied and broadly described herein, an aspect of the present disclosure relates to a host cell comprising the recombinant nucleic acid molecule encoding a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221,222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291,292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361,362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431,432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501,502, 503; 511, 512, 513, respectively; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156,157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226,227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296,297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366,367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436,437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506,507, 508; 516, 517, 518; or 526, 527, 528, respectively.

[0015] As embodied and broadly described herein, an aspect of the present disclosure relates to a method of making an antibody or antigen-binding fragment of an antibody comprising culturing a recombinant host cell comprising a recombinant expression construct comprising an expression control sequence operatively linked to a recombinant nucleic acid molecule encoding a monoclonal antibody or binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221,222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291,292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361,362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431,432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501,502, 503; 511, 512, 513; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186,187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256,257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326,327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396,397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466,467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively, wherein the host cell produces the antibody or antigen-binding fragment of an antibody, and isolating the antibody or antigen-binding fragment of an antibody from the recombinant host cell.BRIEF DESCRIPTION OF THE DRAWINGS

[0016] For a more complete understanding of the features and advantages of the present invention, reference is now made to the detailed description of the invention along with the accompanying figures and in which:

[0017] FIG. 1 is a table that summarizes the binding results of the antibodies of the present invention.DETAILED DESCRIPTION OF THE INVENTION

[0018] While the making and using of various embodiments of the present invention are discussed in detail below, it should be appreciated that the present invention provides many applicable inventive concepts that can be embodied in a wide variety of specific contexts. The specific embodiments discussedherein are merely illustrative of specific ways to make and use the invention and do not delimit the scope of the invention.

[0019] To facilitate the understanding of this invention, a number of terms are defined below. Terms defined herein have meanings as commonly understood by a person of ordinary skill in the areas relevant to the present invention. Terms such as “a”, “an” and “the” are not intended to refer to only a singular entity, but include the general class of which a specific example may be used for illustration. The terminology herein is used to describe specific embodiments of the invention, but their usage does not delimit the invention, except as outlined in the claims.

[0020] As used herein, the term “antibody” refers to an intact antibody or a binding fragment thereof that binds specifically to a target antigen. Binding fragments are produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact antibodies. Binding fragments include Fab, Fab’, F(ab’)2, Fv, and single-chain variable fragment (scFv) antibodies. An antibody substantially inhibits adhesion of a receptor to a counterreceptor when an excess of antibody reduces the quantity of receptor bound to counterreceptor by at least about 20%, 40%, 60% or 80%, and more usually greater than about 85% (as measured in an in vitro competitive binding assay). The term “antibody” is used in the broadest sense, and specifically covers monoclonal antibodies (including full-length antibodies or other bivalent, Fc-region containing antibodies such as bivalent scFv Fc-fiision antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antigen-binding fragments (e.g., Fab, Fab’, F(ab’)2, Fv, scFv) so long as they exhibit the desired biological activity. Antibodies (Abs) and immunoglobulins (Igs) are glycoproteins having the same structural characteristics. The present invention includes monoclonal antibodies (and binding fragments thereof) that are completely recombinant, in other words, where the complementarity determining regions (CDRs) are genetically spliced into a human antibody backbone, often referred to as veneering an antibody. Thus, in certain aspects, the monoclonal antibody is a fully synthesized antibody. In certain embodiments, the monoclonal antibodies (and binding fragments thereof) can be made in bacterial or eukaryotic cells, including plant cells.

[0021] As used herein, the terms “antibody fragment” or “antigen-binding fragment” refer to a portion of a full-length antibody, generally the antigen-binding or variable region, and include Fab, Fab’, F(ab’)2, Fv, and scFv fragments. Papain digestion of antibodies produces two identical antigen-binding fragments, called the Fab fragment, each with a single antigen-binding site, and a residual “Fc” fragment, so-called for its ability to crystallize readily. Pepsin treatment yields an F(ab’)2 fragment that has two antigenbinding fragments which are capable of cross-linking antigen, and a residual other fragment (which is termed pFc’). As used herein, “functional fragment” with respect to antibodies, refers to Fv, F(ab) and F(ab’)2 fragments.

[0022] As used herein, the “Fv” fragment is the minimum antigen-binding fragment that contains a complete antigen recognition and binding site. This region consists of a dimer of one heavy and one light chain variable domain in a tight, non-covalent association (VH-VL dimer). It is in this configuration that the three CDRs of each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody. However, even asingle variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.

[0023] The Fab fragment, also designated as F(ab), also contains the constant domain of the light chain and the first constant domain (CHI) of the heavy chain. Fab’ fragments differ from Fab fragments by the addition of a few residues at the carboxyl terminus of the heavy chain CHI domain including one or more cysteines from the antibody hinge region. Fab’-SH is the designation herein for Fab’ in which the cysteine residue(s) of the constant domains have a free thiol group. F(ab’) fragments are produced by cleavage of the disulfide bond at the hinge cysteines of the F(ab’)2 pepsin digestion product. Additional chemical couplings of antigen-binding fragment are known to those of ordinary skill in the art.

[0024] Native antibodies and immunoglobulins are usually heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each light chain is linked to a heavy chain by at least one covalent disulfide bond; however, the number of disulfide linkages varies between the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has at one end a variable domain (VH) followed by the constant domains. Each light chain has a variable domain at one end (VL) and a constant domain at its other end. The constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light chain variable domain is aligned with the variable domain of the heavy chain. Particular amino acid residues are believed to form an interface between the light and heavy chain variable domains (Clothia et al., J. Mol. Biol. 186, 651-66, 1985); Novotny and Haber, Proc. Natl. Acad. Sci. USA 82 4592-4596 (1985), relevant portions incorporated herein by reference.

[0025] As used herein, an “isolated” antibody is one that has been identified and separated and / or recovered from a component of the environment in which it was produced. Contaminant components of its production environment are materials, that would interfere with diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In certain embodiments, the antibody will be purified as measurable by at least three different methods: 1) to greater than 50% by weight of antibody as determined by the Lowry method, such as more than 75% by weight, or more than 85% by weight, or more than 95% by weight, or more than 99% by weight; 2) to a degree sufficient to obtain at least 10 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, such as at least 15 residues of sequence; or 3) to homogeneity by SDS-PAGE under reducing or non-reducing conditions using Coomasie blue or, preferably, silver stain. Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody’ s natural environment will not be present. Ordinarily, however, isolated antibody will be prepared by at least one purification step.

[0026] As used herein, the terms “antibody mutant” or “antibody variant” refer to an amino acid sequence variant of an antibody wherein one or more of the amino acid residues have been modified. Such mutants necessarily have less than 100% sequence identity or similarity with the amino acid sequence having at least 75% amino acid sequence identity or similarity with the amino acid sequence of either the heavy orlight chain variable domain of the antibody, such as at least 80%, or at least 85%, or at least 90%, or at least 95, 96, 97, 98, or 99%.

[0027] As used herein, the term “variable” in the context of the variable domain of antibodies, refers to the fact that certain portions of the variable domains differ extensively in sequence among antibodies and are used in the binding and specificity of each particular antibody for its particular antigen. However, the variability is not evenly distributed through the variable domains of antibodies. It is concentrated in three segments called complementarity determining regions (CDRs) also known as hypervariable regions both in the light chain and the heavy chain variable domains. There are at least two techniques for determining CDRs: (1) an approach based on cross-species sequence variability (i.e., Kabat et al., Sequences of Proteins of Immunological Interest (National Institute of Health, Bethesda, Md. 1987); and (2) an approach based on crystallographic studies of antigen-antibody complexes (Chothia, C. et al. (1989), Nature 342: 877), or both, that is Chothia plus Kabat. The more highly conserved portions of variable domains are called the framework (FR). The variable domains of native heavy and light chains each comprise four FR regions, largely adopting a [3-sheet configuration, connected by three CDRs, which form loops connecting, and in some cases forming part of, the [3-sheet structure. The CDRs in each chain are held together in close proximity by the FR regions and, with the CDRs from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al.). The constant domains are not involved directly in binding an antibody to its cognate antigen but exhibit various effector function, such as participation of the antibody in antibody-dependent cellular toxicity.

[0028] The light chains of antibodies (immunoglobulin) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino sequences of their constant domain. Depending on the amino acid sequences of the constant domain of their heavy chains, “immunoglobulins” can be assigned to different classes. There are at least five (5) major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG-1, IgG-2, IgG-3, and IgG4; IgA-1 and IgA-2. The subunit structures and three- dimensional configurations of different classes of immunoglobulins are well known.

[0029] As used herein, the term “monoclonal antibody” refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they are synthesized by the hybridoma culture, uncontaminated by other immunoglobulins. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with thepresently disclosed and claimed invention may be made by the hybridoma method first described by Kohler and Milstein, Nature 256, 495 (1975), relevant portions incorporated herein by reference.

[0030] All monoclonal antibodies used in accordance with the presently disclosed and claimed invention will be either (1) the result of a deliberate immunization protocol, as described in more detail hereinbelow; or (2) the result of an immune response that results in the production of antibodies naturally in the course of a disease or cancer.

[0031] The uses of the monoclonal antibodies of the presently disclosed and claimed invention may require administration of such or similar monoclonal antibody to a subject, such as a human. However, when the monoclonal antibodies are produced in a non-human animal, such as a rodent or chicken, administration of such antibodies to a human patient will normally elicit an immune response, wherein the immune response is directed towards the antibodies themselves. Such reactions limit the duration and effectiveness of such a therapy. In order to overcome such a problem, the monoclonal antibodies of the presently disclosed and claimed invention can be “humanized”, that is, the antibodies are engineered such that antigenic portions thereof are removed and like portions of a human antibody are substituted, while the antibodies’ affinity forthe S2 domain of SARS CoV-2 Spike protein from different variants is retained. This engineering may only involve a few amino acids or may include entire framework regions of the antibody, leaving only the complementarity determining regions of the antibody intact. Several methods of humanizing antibodies are known in the art and are disclosed in U.S. Pat. No. 6, 180,370, issued to Queen et al on Jan. 30, 2001; U.S. Pat. No. 6,054,927, issued to Brickell on Apr. 25, 2000; U.S. Pat. No. 5,869,619, issued to Studnicka on Feb. 9, 1999; U.S. Pat. No. 5,861,155, issued to Uin on Jan. 19, 1999; U.S. Pat. No. 5,712,120, issued to Rodriquez et al on Jan. 27, 1998; and U.S. Pat. No. 4,816,567, issued to Cabilly et al on Mar. 28, 1989, relevant portions incorporated herein by reference.

[0032] Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fab, Fab’, F(ab’)2, Fv, scFv or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., 1986; Riechmann et al., 1988; Verhoeyen et al., 1988), by substituting nonhuman (i.e., rodent, chicken) CDRs or CDR sequences forthe corresponding sequences of a human antibody, see, e.g., U.S. Pat. No. 5,225,539. In some instances, Fvframework residues of the human immunoglobulin are replaced by corresponding non-human residues from the donor antibody. Humanized antibodies can also comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of, at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin .

[0033] The presently disclosed and claimed invention further includes a fully human monoclonal antibody variant, binding fragment, and uses thereof, wherein the antigen-biding domain binds specifically to an S2 domain of SARS CoV-2 Spike protein. Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed “human antibodies” or “fully human antibodies” herein. Human monoclonal antibodies can be prepared by, e.g., the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., Hybridoma, 2:7 (1983)) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., PNAS 82:859 (1985)), or as taught herein. Human monoclonal antibodies may be utilized in the practice of the presently disclosed and claimed invention and may be produced by using human hybridomas (see Cote, et al., PNAS 80:2026 (1983)) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985), relevant portions incorporated herein by reference.

[0034] In addition, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example but not by way of limitation, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al., J Biol. Chem. 267: 16007, (1992); Lonberg et al., Nature, 368:856 (1994); Morrison, 1994; Fishwild et al., Nature Biotechnol. 14:845 (1996); Neuberger, Nat. Biotechnol. 14:826 (1996); and Lonberg and Huszar, Int Rev Immunol. 13:65 (1995), relevant portions incorporated herein by reference.

[0035] A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Pat. No. 5,916,771, issued to Hori et al. on Jun. 29, 1999, and incorporated herein by reference. It includes introducing an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell. The hybrid cell expresses an antibody containing the heavy chain and the light chain.

[0036] An antibody or antigen-binding fragment can be generated with an engineered sequence or glycosylation state to confer preferred levels of activity in antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP), or antibody-dependent complement deposition (ADCD) functions as measured by bead-based or cell -based assays or in vivo studies in animal models.

[0037] Alternatively, or additionally, it may be useful to combine amino acid modifications with one or more further amino acid modifications that alter complement component Clq binding and / or the complement-dependent cytotoxicity (CDC) function of the Fc region of an IL-23pl9 binding molecule. The binding polypeptide of particular interest may be one that binds to Clq and displays complementdependent cytotoxicity. Polypeptides with pre-existing Clq binding activity, optionally further having the ability to mediate CDC may be modified such that one or both of these activities are enhanced. Aminoacid modifications that alter Clq and / or modify its complement-dependent cytotoxicity function are described, for example, in W0 / 0042072, which is hereby incorporated by reference.

[0038] An Fc region of an antibody can be designed to alter the effector function, e.g., by modifying Clq binding and / or FcyR binding and thereby changing complement-dependent cytotoxicity (CDC) activity and / or antibody-dependent cell-mediated cytotoxicity (ADCC) activity. These "effector functions" are responsible for activating or diminishing a biological activity (e.g., in a subject). Examples of effector functions include, but are not limited to: Clq binding; CDC; Fc receptor binding; ADCC; phagocytosis; down-regulation of cell surface receptors (e.g., B cell receptor; BCR), etc. Such effector functions may require the Fc region to be combined with a binding domain (e.g., an antibody variable domain) and can be assessed using various assays (e.g., Fc binding assays, ADCC assays, CDC assays, etc.).

[0039] For example, one can generate a variant Fc region of an antibody with improved Clq binding and improved FcyRIII binding (e.g., having both improved ADCC activity and improved CDC activity). Alternatively, if it is desired that effector function be reduced or ablated, a variant Fc region can be engineered with reduced CDC activity and / or reduced ADCC activity. In other embodiments, only one of these activities may be increased, and, optionally, also the other activity reduced (e.g., to generate an Fc region variant with improved ADCC activity, but reduced CDC activity and vice versa).

[0040] A single chain variable fragment (scFv) is a fusion of the variable regions of the heavy and light chains of immunoglobulins, linked together with a short (usually serine, glycine) linker. This chimeric molecule retains the specificity of the original immunoglobulin, despite removal of the constant regions and the introduction of a linker peptide. This modification usually leaves the specificity unaltered. These molecules were created historically to facilitate phage display where it is highly convenient to express the antigen-binding domain as a single peptide. Alternatively, scFv can be created directly from subcloned heavy and light chains derived from a hybridoma or B cell. Single chain variable fragments lack the constant Fc region found in complete antibody molecules, and thus, the common binding sites (e.g., protein A / G) used to purify antibodies. These fragments can often be purified / immobilized using Protein L since Protein L interacts with the variable region of kappa light chains.

[0041] Flexible linkers generally are comprised of helix- and turn-promoting amino acid residues such as alanine, serine, and glycine. However, other residues can function as well. A random linker library was constructed in which the genes for the heavy and light chain variable domains were linked by a segment encoding an 18-amino acid polypeptide of variable composition. The scFv repertoire (approx. 5 x 106different members) is displayed on filamentous phage and subjected to affinity selection with hapten. The population of selected variants exhibited significant increases in binding activity but retained considerable sequence diversity. In certain embodiments, the antigen-binding fragments are further modified to increase their serum half-life by using modified Fc regions or mutations to the various constant regions, as are known in the art.

[0042] In certain embodiments, the antibodies of the present invention are formulated for administration to humans. For example, the antibodies of the present invention can be included in a pharmaceutical composition formulated for an administration that is: intranasal, intrapulmonary, intrabronchial,intravenous, oral, intraadiposal, intraarterial, intraarticular, intracranial, intradermal, intralesional, intramuscular, intrapericardial, intraperitoneal, intrapleural, intravesicular, local, mucosal, parenteral, enteral, subcutaneous, sublingual, topical, transbuccal, transdermal, via inhalation, via injection, in creams, in lipid compositions, via a catheter, via a lavage, via continuous infusion, via infusion, via local delivery, or via localized perfusion, and wherein the composition is a serum, drop, gel, ointment, spray, reservoir, or mist.

[0043] As used herein, the term “substantially purified” refers to isolation of the antibodies or antigenbinding portions thereof of the present invention against SARS-CoV-2 such that the antibodies or antigenbinding portions comprise the majority percent of the sample in which it resides. Typically, in a sample, a substantially purified component comprises 50%, preferably 80%-85%, more preferably 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% ofthe sample. Techniques forpurifying polynucleotides and polypeptides ofinterest are well-known in the art and include, for example, ion-exchange chromatography, affinity chromatography and sedimentation according to density.

[0044] As used herein, the term a “coding sequence” or a sequence which “encodes” the antibodies or antigen-binding portions thereof of the present invention against SARS-CoV-2, refers to a nucleic acid molecule that is transcribed (in the case of DNA) and translated (in the case of mRNA) into a polypeptide when placed under the control of appropriate regulatory sequences (or “control elements”) and in vitro or in vivo. The boundaries of the coding sequence are determined by a start codon at the 5' (amino) terminus and a translation stop codon at the 3' (carboxy) terminus. A coding sequence can include, but is not limited to, cDNA from viral, prokaryotic or eukaryotic mRNA, genomic DNA sequences from viral or prokaryotic DNA, and even synthetic DNA sequences. A transcription termination sequence may be located 3' to the coding sequence.

[0045] As used herein, the term “control elements”, includes, but is not limited to, transcription promoters, transcription enhancer elements, transcription termination signals, polyadenylation sequences (located 3' to the translation stop codon), sequences for optimization of initiation of translation (located 5' to the coding sequence), and translation termination sequences, and / or sequence elements controlling an open chromatin structure.

[0046] As used herein, the term “nucleic acid” includes, but is not limited to, DNA or RNA that encodes the antibodies or antigen-binding portions thereof of the present invention against SARS-CoV-2 of the present invention, whether expressed or optimized for prokaryotic or eukaryotic expression. The term also captures sequences that include any of the known base analogs of DNA and RNA.

[0047] As used herein, the term “operably linked” refers to an arrangement of elements wherein the components so described are configured so as to perform their usual function. Thus, a given promoter operably linked to a coding sequence is capable of effecting the expression of the coding sequence when active. The promoter need not be contiguous with the coding sequence, so long as it functions to direct the expression thereof. Thus, for example, intervening untranslated yet transcribed sequences can be present between the promoter sequence and the coding sequence and the promoter sequence can still be considered “operably linked” to the coding sequence.

[0048] As used herein, the term “recombinant” refers to a polynucleotide that encodes the mutant SARS- CoV-2 spike antibody whether from the viral genome, cDNA, semisynthetic, or synthetic origin which, by virtue of its origin or manipulation: (1) is not associated with all or a portion of the polynucleotide with which it is associated in nature; and / or (2) is linked to a polynucleotide other than that to which it is linked in nature. The term “recombinant” as used with respect to a protein or polypeptide means a polypeptide produced by expression of a recombinant polynucleotide. “Recombinant host cells,” “host cells,” “cells,” “cell lines,” “cell cultures,” and other such terms denoting prokaryotic microorganisms or eukaryotic cell lines cultured as unicellular entities, are used interchangeably, and refer to cells which can be, or have been, used as recipients for recombinant vectors or other transfer DNA, and include the progeny of the original cell which has been transfected. It is understood that the progeny of a single parental cell may not necessarily be completely identical in morphology or in genomic or total DNA complement to the original parent, due to accidental or deliberate mutation. Progeny of the parental cell which are sufficiently similar to the parent to be characterized by the relevant property, such as the presence of a nucleotide sequence encoding a desired peptide, are included in the progeny intended by this definition, and are covered by the above terms.

[0049] Techniques for determining amino acid sequence “similarity” are well known in the art. In general, “similarity” means the exact amino acid to amino acid comparison of two or more polypeptides at the appropriate place, where amino acids are identical or possess similar chemical and / or physical properties such as charge or hydrophobicity. A so-termed “percent similarity” then can be determined between the compared polypeptide sequences. Techniques for determining nucleic acid and amino acid sequence identity also are well known in the art and include determining the nucleotide sequence of the mRNA for that gene (usually via a cDNA intermediate) and determining the amino acid sequence encoded thereby and comparing this to a second amino acid sequence. In general, “identity” refers to an exact nucleotide to nucleotide or amino acid to amino acid correspondence of two polynucleotides or polypeptide sequences, respectively.

[0050] Two or more polynucleotide sequences can be compared by determining their “percent identity.” Two or more amino acid sequences likewise can be compared by determining their “percent identity.” The percent identity of two sequences, whether nucleic acid or peptide sequences, is generally described as the number of exact matches between two aligned sequences divided by the length of the shorter sequence and multiplied by 100. An approximate alignment for nucleic acid sequences is provided by the local homology algorithm of Smith and Waterman, Advances in Applied Mathematics 2:482-489 (1981). This algorithm can be extended to use with peptide sequences using the scoring matrix developed by Dayhoff, Atlas of Protein Sequences and Structure, M. O. Dayhoff ed., 5 suppl. 3:353-358, National Biomedical Research Foundation, Washington, D.C., USA, and normalized by Gribskov, Nucl. Acids Res. 14(6):6745-6763 (1986), relevant portion incorporated herein by reference. Suitable programs for calculating the percent identity or similarity between sequences are generally known in the art.

[0051] As used herein, the term a “vector” refers to a nucleic acid capable of transferring gene sequences to target cells (e.g., bacterial plasmid vectors, viral vectors, non-viral vectors, particulate carriers, andliposomes). Typically, “vector construct,” “expression vector,” and “gene transfer vector,” mean any nucleic acid construct capable of directing the expression of one or more sequences of interest in a host cell. Thus, the term includes cloning and expression vehicles, as well as viral vectors. The term is used interchangeably with the terms “nucleic acid expression vector” and “expression cassette.”

[0052] Many suitable expression systems are commercially available, including, for example, the following: baculovirus expression (Reilly, P. R., et al., BACULO VIRUS EXPRESSION VECTORS: A LABORATORY MANUAL (1992); Beames, et al., Biotechniques 11:378 (1991); Pharmingen; Clontech, Palo Alto, Calif.)), vaccinia expression systems (Earl, P. L., et al., “Expression of proteins in mammalian cells using vaccinia” In Current Protocols in Molecular Biology (F. M. Ausubel, et al. Eds.), Greene Publishing Associates & Wiley Interscience, New York (1991); Moss, B., et al., U.S. Pat. No. 5,135,855, issued Aug. 4, 1992), expression in bacteria (Ausubel, F. M., et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley and Sons, Inc., Media Pa.; Clontech), expression in yeast (Rosenberg, S. and Tekamp-Olson, P., U.S. Pat. No. RE35,749, issued, Mar. 17, 1998, herein incorporated by reference; Shuster, J. R., U.S. Pat. No. 5,629,203, issued May 13, 1997, herein incorporated by reference; Gellissen, G., et al., Antonie Van Leeuwenhoek, 62(l-2):79-93 (1992); Romanos, M. A., et al., Yeast 8(6):423-488 (1992); Goeddel, D. V., Methods in Enzymology 185 (1990); Guthrie, C., and G. R. Fink, Methods in Enzymology 194 (1991)), expression in mammalian cells (Clontech; Gibco-BRL, Ground Island, N.Y.; e.g., Chinese hamster ovary (CHO) cell lines (Haynes, J., et al., Nuc. Acid. Res. 11:687-706 (1983); 1983, Lau, Y. F„ et al., Mol. Cell. Biol. 4: 1469-1475 (1984); Kaufinan, R. J., “Selection and coamplification of heterologous genes in mammalian cells,” in Methods in Enzymology, vol. 185, pp 537- 566. Academic Press, Inc., San Diego Calif. (1991)), and expression in plant cells (plant cloning vectors, Clontech Laboratories, Inc., Palo-Alto, Calif., and Pharmacia LKB Biotechnology, Inc., Pistcataway, N.J.; Hood, E„ et al., J. Bacteriol. 168: 1291-1301 (1986); Nagel, R„ et al., FEMS Microbiol. Lett. 67:325 (1990); An, et al., “Binary Vectors”, and others in Plant Molecular Biology Manual A3: 1-19 (1988); Miki, B. L. A., et al., pp. 249-265, and others in Plant DNA Infectious Agents (Hohn, T., et al., eds.) Springer-Verlag, Wien, Austria, (1987); Plant Molecular Biology: Essential Techniques, P. G. Jones and J. M. Sutton, New York, J. Wiley, 1997; Miglani, Gurbachan Dictionary of Plant Genetics and Molecular Biology, New York, Food Products Press, 1998; Henry, R. J., Practical Applications of Plant Molecular Biology, New York, Chapman & Hall, 1997), relevant portions of any of the above are incorporated herein by reference.

[0053] As used herein, the term “subject” refers to any member of the subphylum chordata, including, but not limited to, humans and other primates, including non-human primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, sheep, pigs, goats and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats and guinea pigs; birds, including domestic, wild and game birds such as chickens, turkeys and other gallinaceous birds, ducks, geese, and the like. The term does not denote a particular age. Thus, both adult and newborn individuals are intended to be covered. The system described above is intended for use in any of the above vertebrate species, since the immune systems of all of these vertebrates operate similarly.

[0054] As used herein, the terms “pharmaceutically acceptable” or “pharmacologically acceptable” refer to a material which is not biologically or otherwise undesirable, i.e., the material may be administered to an individual in a formulation or composition without causing any unacceptable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained.

[0055] As used herein, the term “treatment” refers to any of (i) the prevention of infection or reinfection with a coronavirus using neutralizing antibodies, (ii) the reduction or elimination of symptoms, and (iii) the substantial or complete elimination of infection of a coronavirus or variants thereof. Treatment may be prophylactic (prior to infection) or therapeutic (following infection).

[0056] In certain embodiments, the coronavirus is SARS-CoV-2. In another aspect, the coronavirus is SARS, MERS, 229E (alpha), NL63 (alpha), OC43 (beta), HKU1 (beta), SARS-CoV-2, or an emerging variant thereof. SARS-CoV-2 variants include the Wuhan parental sequence with or without the D614G mutation, Alpha (B. l.1.7 and Q lineages), Beta (B.1.351 and descendent lineages), Gamma (P.l and descendent lineages), Epsilon (B.1.427 and B. 1.429), Eta (B.1.525), Iota (B.1.526), Kappa (B. 1.617.1), Mu (B.1.621, B. 1.621.1), Zeta (P.2), Delta (B. 1.617.2 and AY lineages), and Omicron (B. 1.1.529 or its subvariants, BA.l, BA.2, and BA.3). In another aspect, the mutant coronavirus spike proteins are formed into dimers, trimers, multimers, or nanoparticles. In another aspect, the nanoparticles comprise ferritin nanoparticles, polymeric nanoparticles, or both.

[0057] As used herein, the term “effective dose” refers to that amount of the antibodies or antigen-binding portions thereof of the present invention against SARS-CoV-2 sufficient to induce immunity, to prevent and / or ameliorate an infection or to reduce at least one symptom of an infection and / or to enhance the efficacy of another dose of a SARS-CoV-2 antibody, or prophylactic or therapeutic treatment. An effective dose may refer to the amount of the antibodies or antigen-binding portions thereof of the present invention against SARS-CoV-2 sufficient to delay or minimize the onset of an infection. An effective dose may also refer to the amount of the antibodies or antigen-binding portions thereof of the present invention against SARS-CoV-2 that provides a therapeutic benefit in the treatment or management of an infection. Further, an effective dose is the amount of the antibodies or antigen-binding portions thereof of the present invention against SARS-CoV-2, or in combination with other therapies, that provides a therapeutic benefit in the treatment or management of an infection. An effective dose may also be the amount sufficient to enhance a subject's (e.g., a human's) own immune response against subsequent exposure to SARS-CoV-2. Levels of immunity can be monitored, e.g., by measuring amounts of neutralizing secretory and / or serum antibodies, e.g., by plaque neutralization, complement fixation, enzyme-linked immunosorbent, or microneutralization assay. In the case of a vaccine, an “effective dose” is one that prevents disease and / or reduces the severity of symptoms.

[0058] As used herein, the term “immune stimulator” refers to a compound that enhances an immune response via the body's own chemical messengers (cytokines). These molecules comprise various cytokines, lymphokines and chemokines with immunostimulatory, immunopotentiating, and pro- inflammatory activities, such as interferons, interleukins (e.g., IL-1, IL-2, IL-3, IL-4, IL-12, IL-13); growth factors (e.g., granulocyte -macrophage (GM)-colony stimulating factor (CSF)); and otherimmunostimulatory molecules, such as macrophage inflammatory factor, Flt3 ligand, B7. 1; B7.2, etc. The immune stimulator molecules can be administered with the antibodies or antigen-binding portions thereof of the present invention against SARS-CoV-2, or can be administered separately. Either the protein or an expression vector encoding the protein can be administered to produce an immunostimulatory effect.

[0059] As used herein, the term “protective immune response” or “protective response” refers to an immune response mediated by the antibodies or antigen-binding portions thereof of the present invention against SARS-CoV-2, which is exhibited by a vertebrate (e.g., a human), which prevents or ameliorates an infection or reduces at least one symptom thereof.

[0060] The invention further provides kits, including SARS-CoV-2 antibodies, nucleic acids, agents, drugs and pharmaceutical formulations, packaged into suitable packaging material, optionally in combination with instructions for using the kit components, e.g., instructions for performing a method of detection of the invention. In one non-limiting example, the antibody can be detected by an immunoassay selected from radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), sandwich assays, Western blot, immunoprecipitation, immunohistochemistry, immunofluorescence, antibody microarray, dot blotting, and fluorescence-activated cell sorting (FACS).

[0061] In one embodiment, a kit includes a SARS-CoV-2 antibody, subsequence or fragment and instructions for detecting the S2 domain of the SARS-CoV-2 Spike protein. In another embodiment, a kit includes a SARS-CoV-2 antibody, subsequence or fragment and instructions for treating a subject in need of treatment (e.g., a subject having a disease, disorder, pathology, or condition amendable or that may respond to treatment or therapy) with the SARS-CoV-2 antibody, subsequence or fragment.

[0062] The term "packaging material" refers to a physical structure housing the components of the kit. The packaging material can maintain the components sterilely, and can be made of material commonly used for such purposes (e.g., paper, corrugated fiber, glass, plastic, foil, ampules, etc.). The label or packaging insert can include appropriate written instructions, for example, a diagnostic or treatment method of the invention. Instructions can therefore include instructions for practicing any of the methods of the invention described herein. Thus, in various embodiments, a kit includes a label or packaging insert including instructions for practicing a method of the invention in solution, in vitro, in vivo, or ex vivo. In one aspect, the instructions include administering or delivering the anti-S2 domain of the Spike protein of SARS-CoV-2 antibody, subsequence or binding fragment thereof into a subject locally, regionally or systemically in a treatment or therapeutic method of the invention.

[0063] Instructions may additionally include indications of a satisfactory clinical endpoint or any adverse symptoms or complications that may occur. Instructions may further include storage information, expiration date, or any information required by regulatory agencies such as the Food and Drug Administration for use in a human subject.

[0064] The instructions may be on “printed matter”, e.g., on paper or cardboard within the kit, on a label affixed to the kit or packaging material or attached to a vial or tube containing a component of the kit. Instructions may comprise audio or video medium and additionally be included on a computer readable medium, such as a disk (floppy diskette or hard disk), optical CD such as CD- or DVD-ROM / RAM,magnetic tape, electrical storage media such as RAM and ROM and hybrids of these such as magnetic / optical storage media.

[0065] Invention kits can additionally include a buffering agent, a preservative, or a stabilizing agent. The kit can also include control components for assaying for activity, e.g., a control sample or a standard. Each component of the kit can be enclosed within an individual container or in a mixture and all of the various containers can be within single or multiple packages.

[0066] In accordance with the invention further provided are cell -free (e.g., in solution, in solid phase) and cell-based (e.g., in vitro or in vivo) methods of screening, detecting and identifying SARS-CoV-2. The methods can be performed in solution, in vitro using a biological material or sample, and in vivo, for example, a sample of cells from an animal. In one embodiment, a method includes contacting a biological material or sample with an antibody that binds to SARS-CoV-2 under conditions allowing binding of the antibody to SARS-CoV-2; and assaying for binding of the antibody to SARS-CoV-2. The binding of the antibody to SARS-CoV-2 detects the presence of SARS-CoV-2. In one aspect, SARS-CoV-2 is present in a cell or tissue. In another aspect, the biological material or sample is obtained from a mammalian subject.

[0067] As used herein, the term “contacting” when used in reference to a composition such as a protein (e.g., SARS-CoV-2 antibody), material, sample, or treatment, means a direct or indirect interaction between the composition (e.g., SARS-CoV-2 antibody) and the other referenced entity. A particular example of direct interaction is binding. A particular example of an indirect interaction is where the composition acts upon an intermediary molecule, which in turn acts upon the referenced entity. Thus, for example, contacting a cell (e.g., a lymphocyte) with the SARS-CoV-2 antibody includes allowing the antibody to bind to the cell (e.g., through binding to SARS-CoV-2), or allowing the antibody to act upon an intermediary that in turn acts upon the cell.

[0068] As used herein, the terms “assaying” and “measuring” and grammatical variations thereof are used interchangeably herein and refer to either qualitative or quantitative determinations, or both qualitative and quantitative determinations. When the terms are used in reference to binding, any means of assessing the relative amount, affinity or specificity of binding is contemplated, including the various methods set forth herein and known in the art. For example, SARS-CoV-2 antibody binding to SARS-CoV-2 can be assayed or measured by an ELISA assay.

[0069] The practice of the present invention employs, unless otherwise indicated, conventional methods of chemistry, biochemistry, molecular biology, immunology and pharmacology, within the skill of the art to make the antibodies or antigen-binding portions thereof of the present invention against SARS-CoV-2. Such techniques are explained fully in the literature. See, e.g., Remington's Pharmaceutical Sciences, 18th Edition (Easton, Pa.: Mack Publishing Company, 1990); Methods In Enzymology (S. Colowick and N. Kaplan, eds., Academic Press, Inc.); and Handbook of Experimental Immunology, Vols. I-IV (D. M. Weir and C. C. Blackwell, eds., 1986, Blackwell Scientific Publications); Sambrook, et al., Molecular Cloning: A Laboratory Manual (2nd Edition, 1989); Short Protocols in Molecular Biology, 4th ed. (Ausubel et al. eds., 1999, John Wiley & Sons); Molecular Biology Techniques: An Intensive Laboratory Course, (Ream et al., eds., 1998, Academic Press); PCR (Introduction to Biotechniques Series), 2nd ed. (Newton &Graham eds., 1997, Springer Verlag); Fundamental Virology, Second Edition (Fields & Knipe eds., 1991, Raven Press, New York), relevant portion incorporated herein by reference.

[0070] Antibody sequences:

[0071] Heavy Chain Complementarity Determining Regions (CDRH1 to CDRH3)

[0072] Light Chain Complementarity Determining Regions (CDRH1 to CDRH3)

[0073] Heavy Chain Amino Acid and Nucleic Acid SequencesLight Chain Amino Acid and Nucleic Acid Sequences

[0074] As embodied and broadly described herein, an aspect of the present disclosure relates to a monoclonal antibody or antigen-binding fragment thereof antibody comprising, consisting essentially of, or consisting of: heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231,232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301,302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371,372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441,442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511,512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168;176, 177, 178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238;246, 247, 248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308;316, 317, 318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378;386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448;456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively. In another aspect, the antibody heavy chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524. In another aspect, the antibody light chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529. In another aspect, the antigen-binding fragment is a recombinant single-chain fragment variable (scFV) antibody, Fab fragment, F(ab’)2 fragment, or Fv fragment. In another aspect, the e antibody or antigen-binding fragment is chimeric, humanized, fully human, bispecific, or multimeric. In another aspect, the antibody or antigen-binding fragment comprises an Fc portion mutated to at least one of: eliminate or enhance Fc Receptor (FcR) interactions to change a half-life, increase or decrease antibodydependent cellular cytotoxicity, or increase or decrease complement activation. In another aspect, the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365, 375, 385, 395, 405, 415, 425, 435, 445, 455, 465, 475, 485, 495, 505, 515, or 525. In another aspect, the antibody light chain variable region is encoded by a nucleic acidsequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, or 530. In another aspect, the antibody or antigen-binding fragment is adapted for administration or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen-binding fragment. In another aspect, the monoclonal antibody further comprises a peptide linker in a hinge region between the variable and constant domains of the heavy chain.

[0075] As embodied and broadly described herein, an aspect of the present disclosure relates to a pharmaceutical composition antibody comprising, consisting essentially of, or consisting of: a pharmaceutically acceptable excipient and a therapeutically effective amount of a monoclonal antibody or antigen-binding fragment thereof comprising a heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211,212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281,282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351,352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421,422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491,492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and a light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226,227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296,297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366,367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436,437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506,507, 508; 516, 517, 518; or 526, 527, 528, respectively. In one aspect, the antibody or antigen-binding fragment that binds to an S2 domain of SARS CoV-2 Spike protein. In another aspect, the antibody heavy chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524. In another aspect, the antibody light chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529. In another aspect, the antigen-binding fragment is a recombinant single-chain fragment variable (scFV) antibody, Fab fragment, F(ab’)2 fragment, or Fv fragment. Inanother aspect, the antibody or antigen-binding fragment is chimeric, humanized, fully human, bispecific, or multimeric. In another aspect, the antibody or antigen-binding fragment comprises an Fc portion mutated to at least one of: eliminate or enhance Fc Receptor (FcR) interactions to change a half-life, increase or decrease antibody-dependent cellular cytotoxicity, or increase or decrease complement activation. In another aspect, the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365, 375, 385, 395, 405, 415, 425, 435, 445, 455, 465, 475, 485, 495, 505, 515, or 525. In another aspect, the light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, or 530. In another aspect, the antibody or binding fragment thereof of further comprising a peptide linker in a hinge region between the variable and constant domains of the heavy chain. In another aspect, the antibody or antigen-binding fragment is adapted for administration or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen-binding fragment. In another aspect, the antibody or antigen-binding fragment is formulated for nasal, pulmonary, alveolar, intravenous, administration.

[0076] As embodied and broadly described herein, an aspect of the present disclosure relates to a method of treating SARS-CoV-2 in a subject in need thereof, the method antibody comprising, consisting essentially of, or consisting of: administering to the subject a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222,223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292,293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362,363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432,433;441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502,503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236,237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306,307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376,377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446,447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516,517, 518; or 526, 527, 528, respectively. In one aspect, the antibody or antigen-binding fragment binds toan S2 domain of SARS CoV-2 Spike protein. In another aspect, the antibody heavy chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524. In another aspect, the antibody light chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529. In another aspect, the antigen-binding fragment is a recombinant single-chain fragment variable (scFV) antibody, Fab fragment, F(ab’)2 fragment, or Fv fragment. In another aspect, the antibody or antigen-binding fragment is chimeric, humanized, fully human, bispecific, or multimeric. In another aspect, the antibody or antigen-binding fragment comprises an Fc portion mutated to at least one of: eliminate or enhance Fc Receptor (FcR) interactions to change a half-life, increase or decrease antibodydependent cellular cytotoxicity, or increase or decrease complement activation. In another aspect, the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365, 375, 385, 395, 405, 415, 425, 435, 445, 455, 465, 475, 485, 495, 505, 515, or 525. In another aspect, the antibody light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, or 530. In another aspect, the antibody or antigen-binding fragment is adapted for administration or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen-binding fragment.

[0077] As embodied and broadly described herein, an aspect of the present disclosure relates to a pharmaceutical device suitable for nasal or pulmonary delivery of monoclonal antibody or antigen-binding fragment thereof antibody comprising, consisting essentially of, or consisting of: heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181,182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251,252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321,322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391,392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461,462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36,37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188;196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258;266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328;336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398;406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468;476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively, selected from an inhaler for liquids, a nebulizer, metered-dose inhaler, aerosol, and a dry powder inhaler. In one aspect, the antibody or antigen-binding fragment that binds to an S2 domain of SARS CoV-2 Spike protein.

[0078] As embodied and broadly described herein, an aspect of the present disclosure relates to a method for detecting a Spike protein of SARS-CoV-2 (SARS2-S) antibody comprising, consisting essentially of, or consisting of: obtaining or having obtained a biological sample suspected of comprising a SARS-CoV- 2 virus; contacting the biological sample with a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR) 1 , CDR2, and CDR3 of SEQ ID NOS : 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232,233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302,303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372,373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442,443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512,513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177,178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247,248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317,318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387,388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457,458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively, wherein the antibody or antigen-binding fragment that binds to an S2 domain of SARS CoV-2 Spike protein with a light chain of SEQ ID NO:9; and detecting binding of the antibody or antigenbinding fragment to the SARS-CoV-2 virus. In one aspect, the method further comprises the step of detecting the antibody or antigen-binding fragment is diagnostic for the detection of SARS-CoV-2 in the biological sample. In one aspect, the method further comprises detecting SARS-CoV-2 by performing an immunoassay on the biological sample from a subject; wherein the immunoassay uses an antibody or antigen-binding fragment comprising the monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR) 1 , CDR2, and CDR3 of SEQ ID NOS :1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232,233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302,303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372,373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442,443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512,513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177,178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247,248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317,318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387,388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457,458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively. In another aspect, the immunoassay is selected from radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), sandwich assays, Western blot, immunoprecipitation, immunohistochemistry, immunofluorescence, antibody microarray, dot blotting, and fluorescence- activated cell sorting (FACS).

[0079] As embodied and broadly described herein, an aspect of the present disclosure relates to a kit for detection of a Spike protein of SARS-CoV-2 (SARS2-S) comprising a monoclonal antibody or antigenbinding fragment thereof antibody comprising, consisting essentially of, or consisting of: heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181,182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251,252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321,322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391,392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461,462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188;196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258;266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328;336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398;406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468;476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively,for isolation and / or detection of SARS-CoV-2 in one or more sample types of human or nonhuman origin, including: blood, plasma, serum, saliva, tears, cerebrospinal fluid, lymph, urine, feces, exhaled breath condensate, perspiration, amniotic fluid, exosomes, cell and tissue lysates.

[0080] As embodied and broadly described herein, an aspect of the present disclosure relates to a recombinant nucleic acid molecule encoding an antibody or antigen-binding fragment thereof encoding a monoclonal antibody or antigen-binding fragment thereof antibody comprising, consisting essentially of, or consisting of: heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 11, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231,232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301,302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371,372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441,442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511,512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168;176, 177, 178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238;246, 247, 248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308;316, 317, 318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378;386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448;456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively. In one aspect, the nucleic acid encoding the antigen-binding fragment thereof, wherein the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524. In one aspect, the nucleic acid encoding the antigen-binding fragment thereof, wherein the antibody heavy chain variable region and light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529.

[0081] As embodied and broadly described herein, an aspect of the present disclosure relates to a recombinant expression vector antibody comprising, consisting essentially of, or consisting of: an expression control sequence operatively linked to the recombinant nucleic acid molecule encoding a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementaritydetermining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2 and 3; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 4, 5, and 6, respectively.

[0082] As embodied and broadly described herein, an aspect of the present disclosure relates to a host cell antibody comprising, consisting essentially of, or consisting of: the recombinant nucleic acid molecule encoding a monoclonal antibody or antigen-binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181,182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251,252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321,322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391,392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461,462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513, respectively; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186,187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256,257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326,327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396,397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466,467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively.

[0083] As embodied and broadly described herein, an aspect of the present disclosure relates to a method of making an antibody or antigen-binding fragment of an antibody comprising, consisting essentially of, or consisting of: culturing a recombinant host cell comprising a recombinant expression construct comprising an expression control sequence operatively linked to a recombinant nucleic acid molecule encoding a monoclonal antibody or binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201,202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271,272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341,342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411,412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481,482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236,237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306,307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376,377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446,447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516,517, 518; or 526, 527, 528, respectively, wherein the host cell produces the antibody or antigen-binding fragment of an antibody, and isolating the antibody or antigen-binding fragment of an antibody from the recombinant host cell.

[0084] It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method, kit, reagent, or composition of the invention, and vice versa. Furthermore, compositions of the invention can be used to achieve methods of the invention.

[0085] It will be understood that particular embodiments described herein are shown by way of illustration and not as limitations of the invention. The principal features of this invention can be employed in various embodiments without departing from the scope of the invention. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific procedures described herein. Such equivalents are considered to be within the scope of this invention and are covered by the claims.

[0086] All publications and patent applications mentioned in the specification are indicative of the level of skill of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0087] The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and / or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” The use of the term “or” in the claims is used to mean “and / or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and / or.” Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects.

[0088] As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. In embodiments of any of the compositions and methods provided herein, “comprising” may be replaced with “consisting essentially of’ or “consisting of’. As used herein, the phrase “consisting essentially of’ requires the specified integer(s) or steps as well as those that do not materially affect the character or function of the claimed invention. As used herein, the term “consisting” is used to indicate the presence of the recited integer (e.g., a feature, an element, a characteristic, a property,a method / process step or a limitation) or group of integers (e.g., feature(s), element(s), characteristic(s), propertie(s), method / process steps or limitation(s)) only.

[0089] The term “or combinations thereof’ as used herein refers to all permutations and combinations of the listed items preceding the term. For example, “A, B, C, or combinations thereof’ is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.

[0090] As used herein, words of approximation such as, without limitation, “about”, "substantial" or "substantially" refers to a condition that when so modified is understood to not necessarily be absolute or perfect but would be considered close enough to those of ordinary skill in the art to warrant designating the condition as being present. The extent to which the description may vary will depend on how great a change can be instituted and still have one of ordinary skilled in the art recognize the modified feature as still having the required characteristics and capabilities of the unmodified feature. In general, but subject to the preceding discussion, a numerical value herein that is modified by a word of approximation such as “about” may vary from the stated value by at least ±1, 2, 3, 4, 5, 6, 7, 10, 12 or 15%.

[0091] Additionally, the section headings herein are provided for consistency with the suggestions under 37 CFR 1.77 or otherwise to provide organizational cues. These headings shall not limit or characterize the invention(s) set out in any claims that may issue from this disclosure. Specifically, and by way of example, although the headings refer to a “Field of Invention,” such claims should not be limited by the language under this heading to describe the so-called technical field. Further, a description of technology in the “Background of the Invention” section is not to be construed as an admission that technology is prior art to any invention(s) in this disclosure. Neither is the “Summary” to be considered a characterization of the invention(s) set forth in issued claims. Furthermore, any reference in this disclosure to “invention” in the singular should not be used to argue that there is only a single point of novelty in this disclosure. Multiple inventions may be set forth according to the limitations of the multiple claims issuing from this disclosure, and such claims accordingly define the invention(s), and their equivalents, that are protected thereby. In all instances, the scope of such claims shall be considered on their own merits in light of this disclosure, but should not be constrained by the headings set forth herein.

[0092] All of the compositions and / or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and / or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

[0093] To aid the Patent Office, and any readers of any patent issued on this application in interpreting the claims appended hereto, applicants wish to note that they do not intend any of the appended claims to invoke paragraph 6 of 35 U.S.C. § 112, U.S.C. § 112 paragraph (f), or equivalent, as it exists on the date of filing hereof unless the words “means for” or “step for” are explicitly used in the particular claim.

[0094] For each of the claims, each dependent claim can depend both from the independent claim and from each of the prior dependent claims for each and every claim so long as the prior claim provides a proper antecedent basis for a claim term or element.

Claims

WHAT IS CLAIMED IS:

1. A monoclonal antibody or antigen-binding fragment thereof comprising: a heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS:

1. 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92,93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232,233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302,303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372,373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442,443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512,513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197,198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267,268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337,338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407,408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477,478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively.

2. The monoclonal antibody or antigen-binding fragment thereof of claim 1, wherein the antibody heavy chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524.

3. The monoclonal antibody or antigen-binding fragment thereof of claim 1, wherein the antibody light chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529.

4. The monoclonal antibody or antigen-binding fragment thereof of any one of claims 1 to 2, wherein the antigen-binding fragment is a recombinant single-chain fragment variable (scFV) antibody, Fab fragment, F(ab’)2 fragment, or Fv fragment.

5. The monoclonal antibody or antigen-binding fragment thereof of any one of claims 1 to 4, wherein the antibody or antigen-binding fragment is chimeric, humanized, fully human, bispecific, or multimeric.

6. The monoclonal antibody or antigen-binding fragment thereof of any one of claims 1 to 5, wherein the antibody or antigen-binding fragment comprises an Fc portion mutated to at least one of: eliminate orenhance Fc Receptor (FcR) interactions to change a half-life, increase or decrease antibody-dependent cellular cytotoxicity, or increase or decrease complement activation.

7. The monoclonal antibody or antigen-binding fragment thereof of any one of claims 1 to 5, wherein the antibody or antigen-binding fragment is adapted for administration or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen-binding fragment.

8. The monoclonal antibody or antigen-binding fragment thereof of any one of claims 1 to 7, further comprising a peptide linker in a hinge region between the variable and constant domains of the heavy chain.

9. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of a monoclonal antibody or antigen-binding fragment thereof comprising: heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163;171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232, 233;241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302, 303;311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372, 373;381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442, 443;451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512, 513; or 521, 522, 523, respectively; and a light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197,198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267,268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337,338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407,408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477,478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively.

10. The pharmaceutical composition of claim 9, wherein the antibody heavy chain comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524.

11. The pharmaceutical composition of claim 9, wherein the antibody light chain comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529.

12. The pharmaceutical composition of any one of claims 9 to 11, wherein the antigen-binding fragment is a recombinant single-chain fragment variable (scFV) antibody, Fab fragment, F(ab’)2 fragment, or Fv fragment.

13. The pharmaceutical composition of any one of claims 9 to 12, wherein the antibody or antigenbinding fragment is chimeric, humanized, fully human, bispecific, or multimeric.

14. The pharmaceutical composition of any one of claims 9 to 13, wherein the antibody or antigenbinding fragment comprises an Fc portion mutated to at least one of: eliminate or enhance Fc Receptor (FcR) interactions to change a half-life, increase or decrease antibody-dependent cellular cytotoxicity, or increase or decrease complement activation.

15. The pharmaceutical composition of any one of claims 9 to 14, wherein the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365, 375, 385, 395, 405, 415, 425, 435, 445, 455, 465, 475, 485, 495, 505, 515, or 525.

16. The pharmaceutical composition of any one of claims 9 to 14, wherein the antibody light chain variable region and light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, or 530.

17. The pharmaceutical composition of any one of claims 9 to 15, further comprising a peptide linker in a hinge region between the variable and constant domains of the heavy chain.

18. The pharmaceutical composition of any one of claims 9 to 15, wherein the antibody or antigenbinding fragment is adapted for administration or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen-binding fragment.

19. The pharmaceutical composition of any one of claims 9 to 15, wherein the antibody or antigenbinding fragment is formulated for nasal, pulmonary, alveolar, intravenous, administration.

20. A method of treating SARS-CoV-2 in a subject in need thereof, the method comprising administering to the subject a monoclonal antibody or antigen-binding fragment thereof comprising: a heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223; 231, 232,233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293; 301, 302,303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363; 371, 372,373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433; 441, 442,443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503; 511, 512,513; or 521, 522, 523, respectively; anda light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197,198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267,268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337,338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407,408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477,478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively.

21. The method of claim 20, wherein the antibody heavy chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, 124, 134, 144, 154, 164, 174, 184, 194, 204, 214, 224, 234, 244, 254, 264, 274, 284, 294, 304, 314, 324, 334, 344, 354, 364, 374, 384, 394, 404, 414, 424, 434, 444, 454, 464, 474, 484, 494, 504, 514, or 524.

22. The method of claim 20, wherein the antibody light chain variable region comprises an amino acid sequence at least about 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to an amino acid sequence of SEQ ID NOS: 9, 19, 29, 39, 49, 59, 69, 79, 89, 99, 109, 119, 129, 139, 149, 159, 169, 179, 189, 199, 209, 219, 229, 239, 249, 259, 269, 279, 289, 299, 309, 319, 329, 339, 349, 359, 369, 379, 389, 399, 409, 419, 429, 439, 449, 459, 469, 479, 489, 499, 509, 519, or 529.

23. The method of any one of claims 20 to 21, wherein the antigen-binding fragment is a recombinant single-chain fragment variable (scFV) antibody, Fab fragment, F(ab’)2 fragment, or Fv fragment.

24. The method of any one of claims 20 to 23, wherein the antibody or antigen-binding fragment is chimeric, humanized, fully human, bispecific, or multimeric.

25. The method of any one of claims 20 to 24, wherein the antibody or antigen-binding fragment comprises an Fc portion mutated to at least one of: eliminate or enhance Fc Receptor (FcR) interactions to change a half-life, increase or decrease antibody-dependent cellular cytotoxicity, or increase or decrease complement activation.

26. The method of any one of claims 20 to 25, wherein the antibody heavy chain variable region and light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365, 375, 385, 395, 405, 415, 425, 435, 445, 455, 465, 475, 485, 495, 505, 515, or 525.

27. The method of any one of claims 20 to 25, wherein the antibody light chain variable region and light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, or 530.

28. The method of any one of claims 20 to 26, wherein the antibody or antigen-binding fragment is adapted for administration or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antigen-binding fragment.

29. A pharmaceutical device suitable for nasal or pulmonary delivery of monoclonal antibody or antigen-binding fragment thereof comprising: a heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223;231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293;301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363;371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433;441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503;511, 512, 513; or 521, 522, 523, respectively; and a light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188;196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258;266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328;336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398;406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468;476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively, selected from an inhaler for liquids, a nebulizer, metered-dose inhaler, aerosol, and a dry powder inhaler.

30. A method for detecting a Spike protein of SARS-CoV-2 (SARS2-S) comprising: obtaining or having obtained a biological sample suspected of comprising a SARS-CoV-2 virus; contacting the biological sample with a monoclonal antibody or antigen-binding fragment thereof comprising: a heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223;231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293;301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363;371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433;441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503;511, 512, 513; or 521, 522, 523, respectively; and a light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118;126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188;196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258;266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328;336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398;406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468;476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively; and detecting binding of the antibody or antigen-binding fragment to the SARS-CoV-2 virus.

31. The method of claim 30, further comprising the step of detecting the antibody or antigen-binding fragment is diagnostic for the detection of SARS-CoV-2 in the biological sample.

32. The method of claim 30, further comprising detecting SARS-CoV-2 by performing an immunoassay on the biological sample from a subject; wherein the immunoassay uses an antibody or antigen-binding fragment of any of claims 1 to 19.

33. The method of claim 32, wherein the immunoassay is selected from radioimmunoassay, enzyme- linked immunosorbent assay (ELISA), sandwich assays, Western blot, immunoprecipitation, immunohistochemistry, immunofluorescence, antibody microarray, dot blotting, and fluorescence- activated cell sorting (FACS).

34. A kit for detection of a Spike protein of SARS-CoV-2 (SARS2-S) comprising a monoclonal antibody or antigen-binding fragment thereof comprising: a heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of SEQ ID NOS: , 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222, 223;231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292, 293;301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362, 363;371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432, 433;441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502, 503;511, 512, 513; or 521, 522, 523, respectively; and a light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158; 166, 167, 168; 176, 177, 178; 186, 187, 188;196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228; 236, 237, 238; 246, 247, 248; 256, 257, 258;266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298; 306, 307, 308; 316, 317, 318; 326, 327, 328;336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368; 376, 377, 378; 386, 387, 388; 396, 397, 398;406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438; 446, 447, 448; 456, 457, 458; 466, 467, 468;476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508; 516, 517, 518; or 526, 527, 528, respectively, for isolation and / or detection of SARS-CoV-2 in one or more sample types of human or nonhumanorigin, including: blood, plasma, serum, saliva, tears, cerebrospinal fluid, lymph, urine, feces, exhaled breath condensate, perspiration, amniotic fluid, exosomes, cell and tissue lysates.

35. A recombinant nucleic acid molecule encoding an antibody or antigen-binding fragment thereof of any of claims 1 to 19.

36. The recombinant nucleic acid molecule of claim 38, wherein the nucleic acid molecule encoding the antigen-binding fragment thereof, wherein the antibody heavy chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 5, 15, 25, 35, 45, 55, 65, 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365, 375, 385, 395, 405, 415, 425, 435, 445, 455, 465, 475, 485, 495, 505, 515, or 525.

37. The recombinant nucleic acid molecule of claim 38, wherein the nucleic acid encoding the antigen-binding fragment thereof, wherein the antibody light chain variable region is encoded by a nucleic acid sequence having at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% identical to a nucleic acid of SEQ ID NOS: 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, or 530.

38. A recombinant expression vector comprising an expression control sequence operatively linked to the recombinant nucleic acid molecule of claim 35.

39. A host cell comprising the recombinant nucleic acid molecule of claim 38.

40. A method of making an antibody or antigen-binding fragment of an antibody comprising culturing a host cell comprising a recombinant expression construct comprising an expression control sequence operatively linked to a recombinant nucleic acid molecule encoding a monoclonal antibody or binding fragment thereof comprising heavy chain complementarity determining regions (CDR)1, CDR2, and CDR3 of 1, 2, 3; 11, 12, 13; 21, 22, 23; 31, 32, 33; 41, 42, 43; 51, 52, 53; 61, 62, 63; 71, 72, 73; 81, 82, 83; 91, 92, 93; 101, 102, 103; 111, 112, 113; 121, 122, 123; 131, 132, 133; 141, 142, 143; 151, 152, 153; 161, 162, 163; 171, 172, 173; 181, 182, 183; 191, 192, 193; 201, 202, 203; 211, 212, 213; 221, 222,223; 231, 232, 233; 241, 242, 243; 251, 252, 253; 261, 262, 263; 271, 272, 273; 281, 282, 283; 291, 292,293; 301, 302, 303; 311, 312, 313; 321, 322, 323; 331, 332, 333; 341, 342, 343; 351, 352, 353; 361, 362,363; 371, 372, 373; 381, 382, 383; 391, 392, 393; 401, 402, 403; 411, 412, 413; 421, 422, 423; 431, 432,433;441, 442, 443; 451, 452, 453; 461, 462, 463; 471, 472, 473; 481, 482, 483; 491, 492, 493; 501, 502,503; 511, 512, 513; or 521, 522, 523, respectively; and light chain CDR1, CDR2, and CDR3 of SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; 126, 127, 128; 136, 137, 138; 146, 147, 148; 156, 157, 158;166, 167, 168; 176, 177, 178; 186, 187, 188; 196, 197, 198; 206, 207, 208; 216, 217, 218; 226, 227, 228;236, 237, 238; 246, 247, 248; 256, 257, 258; 266, 267, 268; 276, 277, 278; 286, 287, 288; 296, 297, 298;306, 307, 308; 316, 317, 318; 326, 327, 328; 336, 337, 338; 346, 347, 348; 356, 357, 358; 366, 367, 368;376, 377, 378; 386, 387, 388; 396, 397, 398; 406, 407, 408; 416, 417, 418; 426, 427, 428; 436, 437, 438;446, 447, 448; 456, 457, 458; 466, 467, 468; 476, 477, 478; 486, 487, 488; 496, 497, 498; 506, 507, 508;516, 517, 518; or 526, 527, 528, respectively, wherein the host cell produces the antibody or antigenbinding fragment of an antibody, and isolating the antibody or antigen-binding fragment of an antibody from the recombinant host cell.

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