Anti-sars-cov-2 antibodies and uses thereof

Abstract

Provided herein are modified anti-SARS-COV-2 antibodies or antigen binding fragments thereof having extended half life and optimized immune activities. Disclosed herein is also directed to pharmaceutical compositions comprising the same and a method for treating or preventing a disease in human patients that is caused by or related to the infection of SARS-COV-2.

1 - 34 . (canceled) 
     
     
         35 . An antibody or an antigen-binding fragment thereof having specific binding affinity to receptor binding domain (RBD) of spike protein of SARS-CoV-2, wherein said antibody or antigen-binding domain comprises:
 a. a heavy chain CDR1 (HCDR1) comprising the sequence of SEQ ID NO: 1, a heavy chain CDR2 (HCDR2) comprising the sequence of SEQ ID NO: 2, a heavy chain CDR3 (HCDR3) comprising the sequence of SEQ ID NO: 3; a light chain CDR1 (LCDR1) comprising the sequence of SEQ ID NO: 4, a light chain CDR2 (LCDR2) comprising the sequence of SEQ ID NO: 5, and a light chain CDR3 (LCDR3) comprising the sequence of SEQ ID NO: 6;   b. a HCDR1 comprising the sequence of SEQ ID NO: 11, a HCDR2 comprising the sequence of SEQ ID NO: 12, a HCDR3 comprising the sequence of SEQ ID NO: 13, a LCDR1 comprising the sequence of SEQ ID NO: 14, a LCDR2 comprising the sequence of SEQ ID NO: 15, and a LCDR3 comprising the sequence of SEQ ID NO: 16;   c. a HCDR1 comprising the sequence of SEQ ID NO: 21, a HCDR2 comprising the sequence of SEQ ID NO: 22, a HCDR3 comprising the sequence of SEQ ID NO: 23, a LCDR1 comprising the sequence of SEQ ID NO: 24, a LCDR2 comprising the sequence of SEQ ID NO: 25, and a LCDR3 comprising the sequence of SEQ ID NO: 26;   d. a HCDR1 comprising the sequence of SEQ ID NO: 31, a HCDR2 comprising the sequence of SEQ ID NO: 32, a HCDR3 comprising the sequence of SEQ ID NO: 33, a LCDR1 comprising the sequence of SEQ ID NO: 34, a LCDR2 comprising the sequence of SEQ ID NO: 35, and a LCDR3 comprising the sequence of SEQ ID NO: 36;   e. a HCDR1 comprising the sequence of SEQ ID NO: 41, a HCDR2 comprising the sequence of SEQ ID NO: 42, a HCDR3 comprising the sequence of SEQ ID NO: 43, a LCDR1 comprising the sequence of SEQ ID NO: 44, a LCDR2 comprising the sequence of SEQ ID NO: 45, and a LCDR3 comprising the sequence of SEQ ID NO: 46;   f. a HCDR1 comprising the sequence of SEQ ID NO: 51, a HCDR2 comprising the sequence of SEQ ID NO: 52, a HCDR3 comprising the sequence of SEQ ID NO: 53, a LCDR1 comprising the sequence of SEQ ID NO: 54, a LCDR2 comprising the sequence of SEQ ID NO: 55, and a LCDR3 comprising the sequence of SEQ ID NO: 56;   g. a HCDR1 comprising the sequence of SEQ ID NO: 65, a HCDR2 comprising the sequence of SEQ ID NO: 66, a HCDR3 comprising the sequence of SEQ ID NO: 67, a LCDR1 comprising the sequence of SEQ ID NO: 68, a LCDR2 comprising the sequence of SEQ ID NO: 69, and a LCDR3 comprising the sequence of SEQ ID NO: 70;   h. a HCDR1 comprising the sequence of SEQ ID NO: 75, a HCDR2 comprising the sequence of SEQ ID NO: 76, a HCDR3 comprising the sequence of SEQ ID NO: 77, a LCDR1 comprising the sequence of SEQ ID NO: 78, a LCDR2 comprising the sequence of SEQ ID NO: 79, and a LCDR3 comprising the sequence of SEQ ID NO: 80;   i. a HCDR1 comprising the sequence of SEQ ID NO: 85, a HCDR2 comprising the sequence of SEQ ID NO: 86, a HCDR3 comprising the sequence of SEQ ID NO: 87, a LCDR1 comprising the sequence of SEQ ID NO: 88, a LCDR2 comprising the sequence of SEQ ID NO: 89, and a LCDR3 comprising the sequence of SEQ ID NO: 90;   j. a HCDR1 comprising the sequence of SEQ ID NO: 95, a HCDR2 comprising the sequence of SEQ ID NO: 96, a HCDR3 comprising the sequence of SEQ ID NO: 97, a LCDR1 comprising the sequence of SEQ ID NO: 98, a LCDR2 comprising the sequence of SEQ ID NO: 99, and a LCDR3 comprising the sequence of SEQ ID NO: 100;   k. a HCDR1 comprising the sequence of SEQ ID NO: 105, a HCDR2 comprising the sequence of SEQ ID NO: 106, a HCDR3 comprising the sequence of SEQ ID NO: 107, a LCDR1 comprising the sequence of SEQ ID NO: 108, a LCDR2 comprising the sequence of SEQ ID NO: 109, and a LCDR3 comprising the sequence of SEQ ID NO: 110;   l. a HCDR1 comprising the sequence of SEQ ID NO: 136, a HCDR2 comprising the sequence of SEQ ID NO: 137, a HCDR3 comprising the sequence of SEQ ID NO: 138, a LCDR1 comprising the sequence of SEQ ID NO: 139, a LCDR2 comprising the sequence of SEQ ID NO: 140, and a LCDR3 comprising the sequence of SEQ ID NO: 141;   m. HCDR1 comprising the sequence of SEQ ID NO: 146, a HCDR2 comprising the sequence of SEQ ID NO: 147, a HCDR3 comprising the sequence of SEQ ID NO: 148, a LCDR1 comprising the sequence of SEQ ID NO: 149, a LCDR2 comprising the sequence of SEQ ID NO: 150, and a LCDR3 comprising the sequence of SEQ ID NO: 151;   n. HCDR1 comprising the sequence of SEQ ID NO: 156, a HCDR2 comprising the sequence of SEQ ID NO: 157, a HCDR3 comprising the sequence of SEQ ID NO: 158, a LCDR1 comprising the sequence of SEQ ID NO: 159, a LCDR2 comprising the sequence of SEQ ID NO: 160, and a LCDR3 comprising the sequence of SEQ ID NO: 161;   o. HCDR1 comprising the sequence of SEQ ID NO: 166, a HCDR2 comprising the sequence of SEQ ID NO: 167, a HCDR3 comprising the sequence of SEQ ID NO: 168, a LCDR1 comprising the sequence of SEQ ID NO: 169, a LCDR2 comprising the sequence of SEQ ID NO: 170, and a LCDR3 comprising the sequence of SEQ ID NO: 171;   p. HCDR1 comprising the sequence of SEQ ID NO: 176, a HCDR2 comprising the sequence of SEQ ID NO: 177, a HCDR3 comprising the sequence of SEQ ID NO: 178, a LCDR1 comprising the sequence of SEQ ID NO: 179, a LCDR2 comprising the sequence of SEQ ID NO: 180, and a LCDR3 comprising the sequence of SEQ ID NO: 181;   q. HCDR1 comprising the sequence of SEQ ID NO: 186, a HCDR2 comprising the sequence of SEQ ID NO: 187, a HCDR3 comprising the sequence of SEQ ID NO: 188, a LCDR1 comprising the sequence of SEQ ID NO: 189, a LCDR2 comprising the sequence of SEQ ID NO: 190, and a LCDR3 comprising the sequence of SEQ ID NO: 191;   r. HCDR1 comprising the sequence of SEQ ID NO: 196, a HCDR2 comprising the sequence of SEQ ID NO: 197, a HCDR3 comprising the sequence of SEQ ID NO: 198, a LCDR1 comprising the sequence of SEQ ID NO: 199, a LCDR2 comprising the sequence of SEQ ID NO: 200, and a LCDR3 comprising the sequence of SEQ ID NO: 201;   s. HCDR1 comprising the sequence of SEQ ID NO: 206, a HCDR2 comprising the sequence of SEQ ID NO: 207, a HCDR3 comprising the sequence of SEQ ID NO: 208, a LCDR1 comprising the sequence of SEQ ID NO: 209, a LCDR2 comprising the sequence of SEQ ID NO: 210, and a LCDR3 comprising the sequence of SEQ ID NO: 211;   t. HCDR1 comprising the sequence of SEQ ID NO: 216, a HCDR2 comprising the sequence of SEQ ID NO: 217, a HCDR3 comprising the sequence of SEQ ID NO: 218, a LCDR1 comprising the sequence of SEQ ID NO: 219, a LCDR2 comprising the sequence of SEQ ID NO: 220, and a LCDR3 comprising the sequence of SEQ ID NO: 221;   u. HCDR1 comprising the sequence of SEQ ID NO: 226, a HCDR2 comprising the sequence of SEQ ID NO: 227, a HCDR3 comprising the sequence of SEQ ID NO: 228, a LCDR1 comprising the sequence of SEQ ID NO: 229, a LCDR2 comprising the sequence of SEQ ID NO: 230, and a LCDR3 comprising the sequence of SEQ ID NO: 231;   v. HCDR1 comprising the sequence of SEQ ID NO: 236, a HCDR2 comprising the sequence of SEQ ID NO: 237, a HCDR3 comprising the sequence of SEQ ID NO: 238, a LCDR1 comprising the sequence of SEQ ID NO: 239, a LCDR2 comprising the sequence of SEQ ID NO: 240, and a LCDR3 comprising the sequence of SEQ ID NO: 241;   w. HCDR1 comprising the sequence of SEQ ID NO: 246, a HCDR2 comprising the sequence of SEQ ID NO: 247, a HCDR3 comprising the sequence of SEQ ID NO: 248, a LCDR1 comprising the sequence of SEQ ID NO: 249, a LCDR2 comprising the sequence of SEQ ID NO: 250, and a LCDR3 comprising the sequence of SEQ ID NO: 251;   x. HCDR1 comprising the sequence of SEQ ID NO: 256, a HCDR2 comprising the sequence of SEQ ID NO: 257, a HCDR3 comprising the sequence of SEQ ID NO: 258, a LCDR1 comprising the sequence of SEQ ID NO: 259, a LCDR2 comprising the sequence of SEQ ID NO: 260, and a LCDR3 comprising the sequence of SEQ ID NO: 261;   y. HCDR1 comprising the sequence of SEQ ID NO: 266, a HCDR2 comprising the sequence of SEQ ID NO: 267, a HCDR3 comprising the sequence of SEQ ID NO: 268, a LCDR1 comprising the sequence of SEQ ID NO: 269, a LCDR2 comprising the sequence of SEQ ID NO: 270, and a LCDR3 comprising the sequence of SEQ ID NO: 271;   z. HCDR1 comprising the sequence of SEQ ID NO: 276, a HCDR2 comprising the sequence of SEQ ID NO: 277, a HCDR3 comprising the sequence of SEQ ID NO: 278, a LCDR1 comprising the sequence of SEQ ID NO: 279, a LCDR2 comprising the sequence of SEQ ID NO: 280, a LCDR3 comprising the sequence of SEQ ID NO: 281;   aa. HCDR1 comprising the sequence of SEQ ID NO: 286, a HCDR2 comprising the sequence of SEQ ID NO: 287, a HCDR3 comprising the sequence of SEQ ID NO: 288, a LCDR1 comprising the sequence of SEQ ID NO: 289, a LCDR2 comprising the sequence of SEQ ID NO: 290, a LCDR3 comprising the sequence of SEQ ID NO: 291;   bb. HCDR1 comprising the sequence of SEQ ID NO: 296, a HCDR2 comprising the sequence of SEQ ID NO: 297, a HCDR3 comprising the sequence of SEQ ID NO: 298, a LCDR1 comprising the sequence of SEQ ID NO: 299, a LCDR2 comprising the sequence of SEQ ID NO: 300, a LCDR3 comprising the sequence of SEQ ID NO: 301;   cc. HCDR1 comprising the sequence of SEQ ID NO: 306, a HCDR2 comprising the sequence of SEQ ID NO: 307, a HCDR3 comprising the sequence of SEQ ID NO: 308, a LCDR1 comprising the sequence of SEQ ID NO: 309, a LCDR2 comprising the sequence of SEQ ID NO: 310, a LCDR3 comprising the sequence of SEQ ID NO: 311;   dd. HCDR1 comprising the sequence of SEQ ID NO: 316, a HCDR2 comprising the sequence of SEQ ID NO: 317, a HCDR3 comprising the sequence of SEQ ID NO: 318, a LCDR1 comprising the sequence of SEQ ID NO: 319, a LCDR2 comprising the sequence of SEQ ID NO: 320, a LCDR3 comprising the sequence of SEQ ID NO: 321;   ee. HCDR1 comprising the sequence of SEQ ID NO: 326, a HCDR2 comprising the sequence of SEQ ID NO: 327, a HCDR3 comprising the sequence of SEQ ID NO: 328, a LCDR1 comprising the sequence of SEQ ID NO: 329, a LCDR2 comprising the sequence of SEQ ID NO: 330, a LCDR3 comprising the sequence of SEQ ID NO: 331;   ff. HCDR1 comprising the sequence of SEQ ID NO: 336, a HCDR2 comprising the sequence of SEQ ID NO: 337, a HCDR3 comprising the sequence of SEQ ID NO: 338, a LCDR1 comprising the sequence of SEQ ID NO: 339, a LCDR2 comprising the sequence of SEQ ID NO: 340, a LCDR3 comprising the sequence of SEQ ID NO: 341;   gg. HCDR1 comprising the sequence of SEQ ID NO: 346, a HCDR2 comprising the sequence of SEQ ID NO: 347, a HCDR3 comprising the sequence of SEQ ID NO: 348, a LCDR1 comprising the sequence of SEQ ID NO: 349, a LCDR2 comprising the sequence of SEQ ID NO: 350, a LCDR3 comprising the sequence of SEQ ID NO: 351;   hh. HCDR1 comprising the sequence of SEQ ID NO: 356, a HCDR2 comprising the sequence of SEQ ID NO: 357, a HCDR3 comprising the sequence of SEQ ID NO: 358, a LCDR1 comprising the sequence of SEQ ID NO: 359, a LCDR2 comprising the sequence of SEQ ID NO: 360, a LCDR3 comprising the sequence of SEQ ID NO: 361;   ii. HCDR1 comprising the sequence of SEQ ID NO: 366, a HCDR2 comprising the sequence of SEQ ID NO: 367, a HCDR3 comprising the sequence of SEQ ID NO: 368, a LCDR1 comprising the sequence of SEQ ID NO: 369, a LCDR2 comprising the sequence of SEQ ID NO: 370, a LCDR3 comprising the sequence of SEQ ID NO: 371;   jj. HCDR1 comprising the sequence of SEQ ID NO: 376, a HCDR2 comprising the sequence of SEQ ID NO: 377, a HCDR3 comprising the sequence of SEQ ID NO: 378, a LCDR1 comprising the sequence of SEQ ID NO: 379, a LCDR2 comprising the sequence of SEQ ID NO: 380, a LCDR3 comprising the sequence of SEQ ID NO: 381;   kk. HCDR1 comprising the sequence of SEQ ID NO: 386, a HCDR2 comprising the sequence of SEQ ID NO: 387, a HCDR3 comprising the sequence of SEQ ID NO: 388, a LCDR1 comprising the sequence of SEQ ID NO: 389, a LCDR2 comprising the sequence of SEQ ID NO: 390, a LCDR3 comprising the sequence of SEQ ID NO: 391;   ll. HCDR1 comprising the sequence of SEQ ID NO: 396, a HCDR2 comprising the sequence of SEQ ID NO: 397, a HCDR3 comprising the sequence of SEQ ID NO: 398, a LCDR1 comprising the sequence of SEQ ID NO: 399, a LCDR2 comprising the sequence of SEQ ID NO: 400, a LCDR3 comprising the sequence of SEQ ID NO: 401;   mm. HCDR1 comprising the sequence of SEQ ID NO: 406, a HCDR2 comprising the sequence of SEQ ID NO: 407, a HCDR3 comprising the sequence of SEQ ID NO: 408, a LCDR1 comprising the sequence of SEQ ID NO: 409, a LCDR2 comprising the sequence of SEQ ID NO: 410, a LCDR3 comprising the sequence of SEQ ID NO: 411;   nn. HCDR1 comprising the sequence of SEQ ID NO: 416, a HCDR2 comprising the sequence of SEQ ID NO: 417, a HCDR3 comprising the sequence of SEQ ID NO: 418, a LCDR1 comprising the sequence of SEQ ID NO: 419, a LCDR2 comprising the sequence of SEQ ID NO: 420, a LCDR3 comprising the sequence of SEQ ID NO: 421;   oo. HCDR1 comprising the sequence of SEQ ID NO: 426, a HCDR2 comprising the sequence of SEQ ID NO: 427, a HCDR3 comprising the sequence of SEQ ID NO: 428, a LCDR1 comprising the sequence of SEQ ID NO: 429, a LCDR2 comprising the sequence of SEQ ID NO: 430, a LCDR3 comprising the sequence of SEQ ID NO: 431.   
     
     
         36 . The antibody or an antigen-binding fragment thereof of  claim 35 , wherein said antibody or antigen-binding domain comprises a heavy chain variable region comprises a sequence selected from the group consisting of SEQ ID NO: 7, 17, 27, 37, 47, 57, 61, 71, 81, 91, 101, 111, 142, 152, 162, 172, 182, 192, 202, 212, 222, 232, 242, 252, 262, 272, 282, 292, 302, 312, 322, 332, 342, 352, 362, 372, 382, 392, 402, 412, 422 and 432, or a homologous sequence thereof having at least 80% sequence identity. 
     
     
         37 . The antibody or an antigen-binding fragment thereof of  claim 35 , wherein said antibody or antigen-binding domain comprises a light chain variable region comprises a sequence selected from the group consisting of SEQ ID NO: 8, 18, 28, 38, 48, 58, 62, 72, 82, 92, 102, 112, 143, 153, 163, 173, 183, 193, 203, 213, 223, 233, 243, 253, 263, 273, 283, 293, 303, 313, 323, 333, 343, 353, 363, 373, 383, 393, 403, 413, 423 and 433, or a homologous sequence thereof having at least 80% sequence identity. 
     
     
         38 . The antibody or an antigen-binding fragment thereof of  claim 35 , wherein said antibody or antigen-binding domain comprises a pair of heavy chain variable region and light chain variable region sequences selected from the group consisting of: SEQ ID NOs: 7/8, 17/18, 27/28, 37/38, 47/48, 57/58, 61/62, 71/72, 81/82, 91/92, 101/102, 111/112, and 142/143, 152/153, 162/163, 172/173, 182/183, 192/193, 202/203, 212/213, 222/223, 232/233, 242/243, 252/253, 262/263, 272/273, 282/283, 292/293, 302/303, 312/313, 322/323, 332/333, 342/343, 352/353, 362/363, 372/373, 382/383, 392/393, 402/403, 412/413, 422/423 and 432/433, or a pair of homologous sequences thereof having at least 80% sequence identity yet retaining specific binding affinity to RBD of spike protein of SARS-CoV-2. 
     
     
         39 . The antibody or an antigen-binding fragment thereof of  claim 35 , wherein said antibody or antigen-binding domain comprises at least one amino acid subsequent substitutions in said antigen-binding domain. 
     
     
         40 . The antibody or an antigen-binding fragment thereof of  claim 39 , wherein said subsequent substitution comprises substituting a cysteine residue to a non-cysteine residue. 
     
     
         41 . The antibody or an antigen-binding fragment thereof of  claim 40 , wherein said cysteine residue is substituted with a serine residue. 
     
     
         42 . The antibody or an antigen-binding fragment thereof of  claim 35 , wherein said antibody or antigen-binding domain further comprises an immunoglobulin constant region of human IgG. 
     
     
         43 . The antibody or an antigen-binding fragment thereof of  claim 42 , wherein said antibody or antigen-binding domain comprises at least one amino acid substitutions in said human IgG constant domain, a light chain of said modified antibody, a heavy chain of said antibody, or a combination thereof. 
     
     
         44 . The antibody or an antigen-binding fragment thereof of  claim 43 , wherein said antibody or antigen-binding domain comprises at least one amino acid substitutions in said human IgG constant domain resulting in reduced effector functions relative to a wildtype Fc. 
     
     
         45 . The antibody or an antigen-binding fragment thereof of  claim 44 , wherein said antibody or antigen-binding domain comprises one or more amino acid substitution(s) at a position selected from the group consisting of: 220, 226, 229, 233, 234, 235, 236, 237, 238, 267, 268, 269, 270, 297, 309, 318, 320, 322, 325, 328, 329, 330, and 331 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat. 
     
     
         46 . The antibody or an antigen-binding fragment thereof of  claim 45 , wherein said antibody or antigen-binding domain comprises one or more amino acid substitution(s) selected from the group consisting of 220S, 226S, 228P, 229S, 233P, 234V, 234G, 234A, 234F, 234A, 235A, 235G, 235E, 236E, 236R, 237A, 237K, 238S, 267R, 268A, 268Q, 269R, 297A, 297Q, 297G, 309L, 318A, 322A, 325L, 328R, 330S, 331S and any combination thereof. 
     
     
         47 . The antibody or an antigen-binding fragment thereof of  claim 45 , wherein said antibody or antigen-binding domain comprises a combination of mutations selected from the group consisting of: a) K322A, L234A, and L235A; b) P331S, L234F, and L235E; c) L234A and L235A; c) N297A; d) N297Q; e) N297G; f) L235E; g) L234A and L235A (IgG1); h) F234A and L235A (IgG4); i) H268Q, V309L, A330S and P331S (IgG2); j) V234A, G237A, P238S, H268A, V309L, A330S and P331S (IgG2). 
     
     
         48 . The antibody or an antigen-binding fragment thereof of  claim 43 , wherein said antibody or antigen-binding domain comprises one or more amino acid residue modifications or substitutions resulting in improved binding affinity to neonatal Fc receptor (FcRn) at pH 6.0 while retaining minimal binding at pH 7.4, or increased serum half life of the antibody. 
     
     
         49 . The antibody or an antigen-binding fragment thereof of  claim 48 , wherein said antibody or antigen-binding domain comprises one or more amino acid substitution(s) at a position selected from the group consisting of: 234, 235, 238, 250, 252, 254, 256; 259; 272, 305, 307, 308, 311, 312, 322, 328, 331, 378, 380, 382, 428, 432, 433, 434, 435, 436 and 437, all positions by EU numbering. 
     
     
         50 . The antibody or an antigen-binding fragment thereof of  claim 49 , wherein said antibody or antigen-binding domain comprises one or more amino acid substitution(s) selected from the group consisting of 234F, 235Q, 238D, 250Q, 252T, 252Y, 254T, 256E, 259I, 272A, 305A, 307A, 308F, 311A, 322Q, 328E, 331S, 380A, 428L, 432C, 433K, 433S, 434S, 434Y, 434F, 434W, 434A, 435H, 436L, 437C and any combination thereof. 
     
     
         51 . The antibody or an antigen-binding fragment thereof of  claim 50 , wherein said antibody or antigen-binding domain has increased serum half-life or improved pH-dependent binding to FcRn and comprises a combination of mutations selected from the group consisting of: a) M428L and N434S; b) P238D and L328E; c) M252Y, S254T and T256E; d) L234F, L235Q, K322Q, M252T, S254T and T256E; e) M428L, V259I and V308F; f) H433K and N434Y; g) H433K and N434F; h) T250Q and M428L; i) T307A, E380A and N434A; and j) 432C, 433S, 434W, 435H, 436L, and 437C. 
     
     
         52 . The antibody or an antigen-binding fragment thereof of claim  34 , wherein said modified antibody or said antigen-binding fragment thereof is a diabody, a Fab, a Fab′, a F(ab′)2, a Fd, an Fv fragment, a disulfide stabilized Fv fragment, a (dsFv)2, a bispecific dsFv, a disulfide stabilized diabody, a single-chain antibody molecule, an scFv dimer, a bispecific scFv dimer, or a multispecific antibody. 
     
     
         53 . The antibody or an antigen-binding fragment thereof of  claim 35 , which is linked to one or more conjugate moieties. 
     
     
         54 . A bispecific antibody comprising one or more of the antigen-binding fragment of  claim 35 . 
     
     
         55 . An isolated polynucleotide encoding the antibody or antigen binding fragment of  claim 35 . 
     
     
         56 . A vector comprising the isolated polynucleotide of  claim 55 . 
     
     
         57 . A host cell comprising the vector of  claim 56 . 
     
     
         58 . A pharmaceutical composition comprising at least one said antibody or an antigen-binding fragment thereof of  claim 35 , at least one nucleic acid encoding said modified antibody or said antigen-binding fragment thereof, or a combination thereof, and one or more pharmaceutically acceptable carriers. 
     
     
         59 . A method for treating or preventing a disease in a subject in need thereof, said method comprising administering an effective dosage of said pharmaceutical composition of  claim 58  to said subject. 
     
     
         60 . The method of  claim 59 , wherein the disease is associated with SARs-CoV-2 infection. 
     
     
         61 . The method of  claim 59 , wherein said pharmaceutical composition is administered to said subject having no symptoms or free from known infections of said SARS-CoV-2, prior to said subject being infected with said SARS-CoV-2, prior to said subject exhibiting any symptoms of the infection of said SARS-CoV-2, or a combination thereof. 
     
     
         62 . The method of  claims 59 , wherein said pharmaceutical composition is administered to said subject via intravenous injection (IV), intramuscular injection (IM), subcutaneous (SC) injection, or a combination thereof. 
     
     
         63 . The method of  claim 59 , wherein said subject is a patient of age 60, 70 or 80 years old or older. 
     
     
         64 . The method of  claim 59 , wherein said effective dosage is determined by a dosing process that comprises determining concentration progression data based on calculated or measured pharmacokinetics (PK), testing plasma concentrations over a testing period of time, predicted plasma concentrations over a prediction period of time, or a combination thereof, of said antibody or said antigen-binding fragment thereof, and producing said effective dosage based on said concentration progression data. 
     
     
         65 . The method of  claim 59 , further comprising administering a pharmaceutically effective amount of one or more bioactive agents to said subject simultaneously or sequentially with said pharmaceutical composition, wherein said bioactive agent comprises a therapeutic agent or a prophylactic agent selected from an anti-viral agent, an antiviral peptide, an anti-viral antibody, an anti-viral compound, an anti-viral cytokine, an anti-viral oligonucleotide, an RNA dependent RNA polymerase inhibitor, a non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), purine nucleoside, antiviral interferon, adamantine antiviral compound, remdesivir, chloroquine, hydroxychloroquine, lopinavir, ritonavir, APN01, favilavir, mesalazine, toremifene, eplerenone, paroxetine, sirolimus, dactinomycin, irbesartan, emodin, mercaptopurine, melatonin, quinacrine, carvedilol, colchicine, camphor, equilin, oxymetholone, nafamosta, camostat, baricitinib, darunavir, ribavirin, galidesivir, BCX-4430, Arbidol, nitazoxanide, one or more derivatives thereof, or any combination thereof.