IL278955A

IL278955A - Anti sars cov-2 antibodies

Info

Publication number: IL278955A
Application number: IL278955A
Authority: IL
Inventors: Tsoory Hezkiah
Original assignee: The Israel Institute Of Biological Res Iibr; Tsoory Hezkiah
Priority date: 2020-11-24
Filing date: 2020-11-24
Publication date: 2022-06-01

Description

Anti SARS Cov-2 antibodies TECHNOLOGICAL FIELD The present invention generally relates to antibodies directed against Severe acute respiratory syndrome coronavirus 2 (SARS Cov-2) surface protein and for methods and uses thereof in treatment and detection of COVID 19.

BACKGROUND ART References considered to be relevant as background to the presently disclosed subject matter are listed below: - Huang et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395, 497-506.

- Mechaly, A. et al. A biolayer interferometry-based assay for rapid and highly sensitive detection of biowarfare agents. Anal Biochem 2016, 506, 22-27.

- Mechaly, A. et al. Novel phage display-derived anti-abrin antibodies confer post-exposure protection against abrin intoxication. Toxins (Basel) 2018, 10.

- Noy-Porat, T. et al. Isolation of anti-ricin protective antibodies exhibiting high affinity from immunized non-human primates. Toxins (Basel) 2016, 8.

- Rosenfeld, R. et al. Isolation and chimerization of a highly neutralizing antibody conferring passive protection against lethal bacillus anthracis infection. PLoS One 2009, 4, e6351.

- Shi, Y., Y. Wang, C. Shao, J. Huang, J. Gan, X. Huang, E. Bucci, M.

Piacentini, G. Ippolito & G. Melino (2020) COVID-19 infection: the perspectives on immune responses. Cell Death Differ March 23 (Epub).

- Zhang, J. J., X. Dong, Y. Y. Cao, Y. D. Yuan, Y. B. Yang, Y. Q. Yan, C. A.

Akdis & Y. D. Gao (2020) Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. February 19 (Epub).

Acknowledgement of the above references herein is not to be inferred as meaning that these are in any way relevant to the patentability of the presently disclosed subject matter.

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS Cov-2) is a newly identified member of the coronavirus family. This virus was first identified in Wuhan, China and is responsible for a world pandemic named COVID-19 (coronavirus disease 2019). The virus represents a strain of RNA viruses that has not been previously identified in humans and could induce symptoms including fever, dry cough, dyspnea, fatigue, and lymphopenia in infected patients. In more severe cases, infections causing viral pneumonia characterized primarily by fever, cough, dyspnea, and bilateral infiltrates may lead to severe acute respiratory syndrome (SARS) and even to death (Zhang et al. 2020). When COVID-19 infects the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro- inflammatory cytokines and chemokines. The virus can also result in a dysregulated immune response and this cytokine storm seems to be associated with disease severity, as it can lead to capillary leak syndrome, progressive lung injury, respiratory failure and acute respiratory distress syndrome (ARDS) (Zhang et al. 2020; Huang et al. 2020; Shi et al. 2020).

GENERAL DESCRIPTION The present invention provides an isolated monoclonal antibody or antigen- binding fragment thereof which binds to Severe acute respiratory syndrome coronavirus 2 (SARS Cov-2) spike protein, wherein said antibody comprises: a. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 33, CDRH2 denoted by SEQ ID NO. 34, CDRH3 denoted by SEQ ID NO. 35, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 36, a CDRL2 denoted by SEQ ID NO. 37, and a CDRL3 denoted by SEQ ID NO. 38; or b. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 39, CDRH2 denoted by SEQ ID NO. 40, CDRH3 denoted by SEQ ID NO. 41, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 42, a CDRL2 denoted by SEQ ID NO. 43, and a CDRL3 denoted by SEQ ID NO. 44; or c. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 45, CDRH2 denoted by SEQ ID NO. 46, CDRH3 denoted by SEQ ID NO. 47, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 48, a CDRL2 denoted by SEQ ID NO. 49, and a CDRL3 denoted by SEQ ID NO. 50; or d. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 51, CDRH2 denoted by SEQ ID NO. 52, CDRH3 denoted by SEQ ID NO. 53, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 54, a CDRL2 denoted by SEQ ID NO. 55, and a CDRL3 denoted by SEQ ID NO. 56; or e. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 57, CDRH2 denoted by SEQ ID NO. 58, CDRH3 denoted by SEQ ID NO. 59, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 60, a CDRL2 denoted by SEQ ID NO. 61, and a CDRL3 denoted by SEQ ID NO. 62; or f. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 63, CDRH2 denoted by SEQ ID NO. 64, CDRH3 denoted by SEQ ID NO. 65, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 66, a CDRL2 denoted by SEQ ID NO. 67, and a CDRL3 denoted by SEQ ID NO. 68; or g. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 69, CDRH2 denoted by SEQ ID NO. 70, CDRH3 denoted by SEQ ID NO. 71, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 72, a CDRL2 denoted by SEQ ID NO. 73, and a CDRL3 denoted by SEQ ID NO. 74; or h. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 75, CDRH2 denoted by SEQ ID NO. 76, CDRH3 denoted by SEQ ID NO. 77, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 78, a CDRL2 denoted by SEQ ID NO. 79, and a CDRL3 denoted by SEQ ID NO. 80; or i. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 201, CDRH2 denoted by SEQ ID NO. 202, CDRH3 denoted by SEQ ID NO. 203, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 204, a CDRL2 denoted by SEQ ID NO. 205, and a CDRL3 denoted by SEQ ID NO. 206; or j. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 207, CDRH2 denoted by SEQ ID NO. 208, CDRH3 denoted by SEQ ID NO. 209, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 210, a CDRL2 denoted by SEQ ID NO. 211, and a CDRL3 denoted by SEQ ID NO. 212; or k. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 213, CDRH2 denoted by SEQ ID NO. 214, CDRH3 denoted by SEQ ID NO. 215, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 216, a CDRL2 denoted by SEQ ID NO. 217, and a CDRL3 denoted by SEQ ID NO. 218; or l. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 219, CDRH2 denoted by SEQ ID NO. 220, CDRH3 denoted by SEQ ID NO. 221, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 222, a CDRL2 denoted by SEQ ID NO. 223, and a CDRL3 denoted by SEQ ID NO. 224; or m. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 225, CDRH2 denoted by SEQ ID NO. 226, CDRH3 denoted by SEQ ID NO. 227, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 228, a CDRL2 denoted by SEQ ID NO. 229, and a CDRL3 denoted by SEQ ID NO. 230; or n. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 231, CDRH2 denoted by SEQ ID NO. 232, CDRH3 denoted by SEQ ID NO. 233, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 234, a CDRL2 denoted by SEQ ID NO. 235, and a CDRL3 denoted by SEQ ID NO. 236; or o. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 237, CDRH2 denoted by SEQ ID NO. 238, CDRH3 denoted by SEQ ID NO. 239, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 240, a CDRL2 denoted by SEQ ID NO. 241, and a CDRL3 denoted by SEQ ID NO. 242; or p. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 243, CDRH2 denoted by SEQ ID NO. 244, CDRH3 denoted by SEQ ID NO. 245, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 246, a CDRL2 denoted by SEQ ID NO. 247, and a CDRL3 denoted by SEQ ID NO. 248; or q. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 249, CDRH2 denoted by SEQ ID NO. 250, CDRH3 denoted by SEQ ID NO. 251, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 252, a CDRL2 denoted by SEQ ID NO. 253, and a CDRL3 denoted by SEQ ID NO. 254; or r. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 255, CDRH2 denoted by SEQ ID NO. 256, CDRH3 denoted by SEQ ID NO. 257, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 258, a CDRL2 denoted by SEQ ID NO. 259, and a CDRL3 denoted by SEQ ID NO. 260; or s. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 261, CDRH2 denoted by SEQ ID NO. 262, CDRH3 denoted by SEQ ID NO. 263, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 264, a CDRL2 denoted by SEQ ID NO. 265, and a CDRL3 denoted by SEQ ID NO. 266; or t. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 267, CDRH2 denoted by SEQ ID NO. 268, CDRH3 denoted by SEQ ID NO. 269, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 270, a CDRL2 denoted by SEQ ID NO. 271, and a CDRL3 denoted by SEQ ID NO. 272; or u. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 273, CDRH2 denoted by SEQ ID NO. 274, CDRH3 denoted by SEQ ID NO. 275, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 276, a CDRL2 denoted by SEQ ID NO. 277, and a CDRL3 denoted by SEQ ID NO. 278; or v. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 279, CDRH2 denoted by SEQ ID NO. 280, CDRH3 denoted by SEQ ID NO. 281, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 282, a CDRL2 denoted by SEQ ID NO. 283, and a CDRL3 denoted by SEQ ID NO. 284; or w. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 285, CDRH2 denoted by SEQ ID NO. 286, CDRH3 denoted by SEQ ID NO. 287, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 288, a CDRL2 denoted by SEQ ID NO. 289, and a CDRL3 denoted by SEQ ID NO. 290; or x. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 291, CDRH2 denoted by SEQ ID NO. 292, CDRH3 denoted by SEQ ID NO. 293, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 294, a CDRL2 denoted by SEQ ID NO. 295, and a CDRL3 denoted by SEQ ID NO. 296; or y. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 297, CDRH2 denoted by SEQ ID NO. 298, CDRH3 denoted by SEQ ID NO. 299, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 300, a CDRL2 denoted by SEQ ID NO. 301, and a CDRL3 denoted by SEQ ID NO. 302; or z. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 303, CDRH2 denoted by SEQ ID NO. 304, CDRH3 denoted by SEQ ID NO. 305, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 306, a CDRL2 denoted by SEQ ID NO. 307, and a CDRL3 denoted by SEQ ID NO. 308.

In some embodiments the isolated monoclonal antibody according to the invention is wherein said antibody comprises a heavy chain variable region and a light chain variable region, wherein: a. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 1 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 2; or b. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 3 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 4; or c. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 5 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 6; or d. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 7 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 8; or e. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 9 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 10; or f. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 11 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 12; or g. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 13 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 14; or h. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 15 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 16; or i. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 81 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 82; or j. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 83 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 84; or k. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 85 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 86; or l. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 87 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 88; or m. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 89 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 90; or n. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 91 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 92; or o. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 93 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 94; or p. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 95 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 96; or q. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 97 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 98; or r. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 99 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 100; or s. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 101 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 102; or t. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 103 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 104; or u. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 105 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 106; or v. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 107 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 108; or w. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 109 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 110; or x. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 111 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 112; or y. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 113 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 114; or z. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 115 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 116.

In other embodiments the isolated monoclonal antibody according to the invention is wherein said antibody comprises: a. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 17 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 18, or a variant thereof; or b. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 19 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 20, or a variant thereof; or c. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 21 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 22, or a variant thereof; or d. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 23 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 24, or a variant thereof; or e. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 25 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 26, or a variant thereof; or f. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 27 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 28, or a variant thereof; or g. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 29 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 30, or a variant thereof; or h. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 31 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 32, or a variant thereof; or i. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 141 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 142, or a variant thereof; or j. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 143 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 144, or a variant thereof; or k. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 145 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 146, or a variant thereof; or l. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 147 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 148, or a variant thereof; or m. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 149 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 150, or a variant thereof; or n. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 151 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 152, or a variant thereof; or o. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 153 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 154, or a variant thereof; or p. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 155 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 156, or a variant thereof; or q. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 157 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 158, or a variant thereof; or r. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 159 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 160, or a variant thereof; or s. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 161 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 162, or a variant thereof; or t. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 163 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 164, or a variant thereof; or u. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 165 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 166, or a variant thereof; or v. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 167 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 168, or a variant thereof; or w. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 169 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 170, or a variant thereof; or x. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 171 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 172, or a variant thereof; or y. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 173 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 174, or a variant thereof; or z. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 175 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 176, or a variant thereof.

In certain embodiments the isolated monoclonal antibody or antigen-binding fragment thereof according to the present invention is wherein said antibody or antigen- binding fragment thereof binds to at least one of the Receptor binding domain (RBD) or the S1 subunit of the spike protein.

In another aspect the present invention provides an isolated monoclonal antibody or antigen-binding fragment thereof which binds to Severe acute respiratory syndrome coronavirus 2 (SARS Cov-2) spike protein, wherein said antibody comprises: a. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 309, CDRH2 denoted by SEQ ID NO. 310, CDRH3 denoted by SEQ ID NO. 311, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 312, a CDRL2 denoted by SEQ ID NO. 313, and a CDRL3 denoted by SEQ ID NO. 314; or b. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 315, CDRH2 denoted by SEQ ID NO. 316, CDRH3 denoted by SEQ ID NO. 317, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 318, a CDRL2 denoted by SEQ ID NO. 319, and a CDRL3 denoted by SEQ ID NO. 320; or c. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 321, CDRH2 denoted by SEQ ID NO. 322, CDRH3 denoted by SEQ ID NO. 323, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 324, a CDRL2 denoted by SEQ ID NO. 325, and a CDRL3 denoted by SEQ ID NO. 326; or d. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 327, CDRH2 denoted by SEQ ID NO. 328, CDRH3 denoted by SEQ ID NO. 329, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 330, a CDRL2 denoted by SEQ ID NO. 331, and a CDRL3 denoted by SEQ ID NO. 332; or e. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 333, CDRH2 denoted by SEQ ID NO. 334, CDRH3 denoted by SEQ ID NO. 335, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 336, a CDRL2 denoted by SEQ ID NO. 337, and a CDRL3 denoted by SEQ ID NO. 338; or f. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 339, CDRH2 denoted by SEQ ID NO. 340, CDRH3 denoted by SEQ ID NO. 341, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 342, a CDRL2 denoted by SEQ ID NO. 343, and a CDRL3 denoted by SEQ ID NO. 344; or g. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 345, CDRH2 denoted by SEQ ID NO. 346, CDRH3 denoted by SEQ ID NO. 347, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 348, a CDRL2 denoted by SEQ ID NO. 349, and a CDRL3 denoted by SEQ ID NO. 350; or h. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 351, CDRH2 denoted by SEQ ID NO. 352, CDRH3 denoted by SEQ ID NO. 353, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 354, a CDRL2 denoted by SEQ ID NO. 355, and a CDRL3 denoted by SEQ ID NO. 356; or i. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 357, CDRH2 denoted by SEQ ID NO. 358, CDRH3 denoted by SEQ ID NO. 359, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 360, a CDRL2 denoted by SEQ ID NO. 361, and a CDRL3 denoted by SEQ ID NO. 362; or j. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 363, CDRH2 denoted by SEQ ID NO. 364, CDRH3 denoted by SEQ ID NO. 365, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 366, a CDRL2 denoted by SEQ ID NO. 367, and a CDRL3 denoted by SEQ ID NO. 368; or k. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 369, CDRH2 denoted by SEQ ID NO. 370, CDRH3 denoted by SEQ ID NO. 371, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 372, a CDRL2 denoted by SEQ ID NO. 373, and a CDRL3 denoted by SEQ ID NO. 374; or l. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 375, CDRH2 denoted by SEQ ID NO. 376, CDRH3 denoted by SEQ ID NO. 377, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 378, a CDRL2 denoted by SEQ ID NO. 379, and a CDRL3 denoted by SEQ ID NO. 380.

In certain embodiments, the isolated monoclonal antibody of the invention comprises a heavy chain variable region and a light chain variable region, wherein: a. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 117 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 118; or b. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 119 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 120; or c. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 121 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 122; or d. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 123 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 124; or e. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 125 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 126; or f. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 127 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 128; or g. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 129 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 130; or h. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 131 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 132; or i. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 133 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 134; or j. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 135 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 136; or k. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 137 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 138; or l. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 139 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 140.

In other embodiments, the isolated monoclonal antibody of the invention comprises: a. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 177 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 178, or a variant thereof; or b. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 179 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 180, or a variant thereof; or c. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 181 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 182, or a variant thereof; or d. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 183 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 184, or a variant thereof; or e. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 185 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 186, or a variant thereof; or f. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 187 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 188, or a variant thereof; or g. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 189 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 190, or a variant thereof; or h. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 191 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 192, or a variant thereof; or i. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 193 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 194, or a variant thereof; or j. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 195 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 196, or a variant thereof; or k. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 197 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 198, or a variant thereof; or l. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 199 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 200.

In some embodiments, the isolated monoclonal antibody or antigen-binding fragment thereof binds to the N terminal domain (NTD) of the spike protein.

In various embodiments the isolated monoclonal antibody or antigen-binding fragment thereof according to the invention is wherein said antibody or antigen-binding fragment thereof binds the S1 subunit of the spike protein with a K of about 1 pM to D about 100 nM.

In other embodiments the isolated monoclonal antibody or antigen-binding fragment thereof according to the present invention is wherein said antibody or antigen- binding fragment thereof inhibits the SARS CoV-2 ability to infect mammalian cells.

In various embodiments the isolated monoclonal antibody or antigen-binding fragment thereof according to the present invention is wherein said antibody or antigen- binding fragment thereof is a single-chain Fv-Fc(scFv-Fc) molecule, single-chain Fv (scFv), Fv, heavy chain variable region, light chain variable region, Fab, F(ab) ′ or any 2 combination thereof.

In certain specific embodiments the isolated monoclonal antibody or antigen- binding fragment thereof according to the present invention is wherein said antibody or antigen-binding fragment thereof is a scFv-Fc molecule.

In further embodiments the isolated monoclonal antibody or antigen-binding fragment thereof according to the present invention is wherein said antibody is a neutralizing antibody.

The present invention further provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding an antibody or any antigen-binding fragment thereof as herein defined.

By a further aspect thereof the present invention provides an expression vector comprising the isolated nucleic acid molecule according to the present invention.

The present invention further provides a host cell transfected with the expression vector as herein defined.

By still another one of its aspects the present invention provides an immunoconjugate comprising the antibody or antigen-binding fragment thereof according to the present invention and an additional therapeutic agent.

The present invention further provides a pharmaceutical composition comprising as an active ingredient at least one isolated monoclonal antibody or antigen-binding fragment thereof, or immunoconjugate according to the invention, and a pharmaceutically acceptable carrier, excipient, or diluent.

In some embodiment the pharmaceutical composition according to the present invention further comprises an additional therapeutic agent.

In one embodiment, the pharmaceutical composition according to the present invention comprises a combination of at least one antibody directed against the RBD and at least one antibody directed against the NTD of the spike protein of SARS Cov-2.

Still further the present invention provides a method of prophylaxis, treatment or amelioration of SARS Cov-2 infection comprising administering to a subject in need thereof a therapeutically effective amount of the isolated monoclonal antibody or antigen- binding fragment thereof, the immunoconjugate or the pharmaceutical composition according to the present invention.

In some embodiments the method according to the present invention is wherein said method further comprises administering to a subject in need thereof an additional therapeutic agent.

The present invention further provides a method of inhibiting the SARS CoV-2 ability to infect mammalian cells in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the isolated monoclonal antibody or antigen-binding fragment thereof, the immunoconjugate or the pharmaceutical composition according to the present invention.

In some embodiments the method according to the present invention is wherein said isolated monoclonal antibody or antigen-binding fragment thereof, immunoconjugate or said pharmaceutical composition is administered to said subject before or after exposure to SARS CoV-2.

The present invention further provides a method of detecting SARS Cov-2 in a sample, said method comprising: a. contacting said sample with the isolated monoclonal antibody or antigen-binding fragment thereof according to the present invention; and b. detecting said isolated monoclonal antibody or any antigen- binding fragment thereof; wherein the presence of said isolated monoclonal antibody or any antigen- binding fragment thereof indicates the presence of SARS Cov-2 in said biological sample.

In some embodiments the method of detecting as herein defined is wherein said sample is a biological sample obtained from a subject.

The present invention further provides the isolated monoclonal antibody or antigen-binding fragment thereof according to the present inevtnion, the immunoconjugate or the pharmaceutical composition as herein defined for use in a method of prophylaxis, treatment or amelioration of SARS Cov-2 infection, said method comprising administering to a subject in need thereof a therapeutically effective amount of said isolated monoclonal antibody or antigen-binding fragment thereof, immunoconjugate or said pharmaceutical composition.

In various embodiments the isolated monoclonal antibody or antigen-binding fragment thereof, or immunoconjugate for use according to the invention is wherein said method further comprises administering to a subject in need thereof an additional therapeutic agent.

The present invention further provides the isolated monoclonal antibody or antigen-binding fragment thereof according to the present invention, the immunoconjugate or the pharmaceutical composition as herein defined for use in a method of inhibiting the SARS CoV-2 ability to infect cells in a subject, said method comprising administering to a subject in need thereof a therapeutically effective amount of said isolated monoclonal antibody or antigen-binding fragment thereof, immunoconjugate or said pharmaceutical composition.

In some embodiments the isolated monoclonal antibody or antigen-binding fragment thereof, the immunoconjugate or the pharmaceutical composition for use according to the invention is wherein said method comprising administering said isolated monoclonal antibody or antigen-binding fragment thereof, immunoconjugate or said pharmaceutical composition to said subject before or after exposure to SARS CoV-2.

The present invention further provides a kit for detecting SARS Cov-2 infection comprising: (a) at least one isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-9; (b) means for detection of said isolated monoclonal antibody; and optionally (c) instructions for use of said kit.

The present invention further provides use of the isolated monoclonal antibody or antigen-binding fragment thereof, the immunoconjugate or the pharmaceutical composition according to the present invention in the preparation of a medicament for the prophylaxis, treatment or amelioration of SARS Cov-2 infection.

Still further the present invention provides the use of the isolated monoclonal antibody or antigen-binding fragment thereof, the immunoconjugate or the pharmaceutical composition as herein defined in the preparation of a medicament for inhibiting the SARS CoV-2 ability to infect mammalian cells in a subject.

BRIEF DESCRIPTION OF THE DRAWINGS In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which: Figure 1 is a bar graph showing the binding specificities of the indicated anti SARS CoV-2 antibodies. The indicated antibodies (10 g/ml) were incubated with ELISA plates coated with the purified SARS CoV-2 proteins receptor binding domain (RBD), S1 subunit (S1), S2 subunit (S2), N-terminal domain (NTD) and the spike protein (SPIKE).

Figure 2 shows binding curves of the indicated anti SARS CoV-2 antibodies.

Increasing concentrations of the indicated antibodies were incubated with ELISA plates coated with the purified S1 subunit. Binding is expressed as percentage (%) of maximal (Bmax) binding to facilitate the calculations of each antibody affinity (KD).

Figure 3 is a bar graph showing an in vitro SARS CoV-2 neutralization assay.

Virus (150 pfu/ml) was incubated with 100 g/ml of each one of the indicated antibodies and the mixture was added to VERO-E6 cells. Virus mediated plaques were determined 48 hours later, and neutralization potency was calculated by comparison to plaque formation in the absence of antibodies.

Figure 4A and 4B are graphs showing percent neutralization of live SARS-Cov- 2 by the indicated anti SARS CoV-2 antibodies, as a function of antibody concentration (µg/ml). Fig. 4A shows antibodies directed to the SARS-Cov-2 receptor binding domain (RBD). Fig. 4B shows antibodies directed to the SARS CoV-2 N-terminal domain (NTD).

DETAILED DESCRIPTION OF EMBODIMENTS The present invention is based on the production of anti SARS Cov-2 antibodies.

Specific and high-affinity antibodies were prepared from blood samples of human patients recovering from COVID-19, by efficient screening methods using phage-display libraries.

Based on the identification of eight high-affinity antibodies directed to SARS Cov-2, termed herein MD17, MD29, MD45, MD47, MD62, MD63, MD65, and MD67, single chain Fv-Fc (scFv-Fc) antibodies were prepared. The anti- SARS Cov-2 scFv-Fc antibodies herein described were capable of binding to SARS Cov-2 and neutralize it, as demonstrated by the plaque reduction neutralization assay presented below. Furthermore, the anti- SARS Cov-2 antibodies herein described were shown to bind purified SARS Cov-2 protein components, namely the S1 subunit and more specifically, the receptor binding domain (RBD), both of which are regions within the viral spike protein.

Additional single chain Fv-Fc (scFv-Fc) antibodies directed to SARS Cov-2 Spike were prepared. The antibodies termed herein BL1, BL2, BL3, BL5, BL6, BL7, BL8, BL9, BL10, BL11, BL12, BLK2, BLK3, BLK10, BLK14, BLK15, BLK21 and BLK23 are directed to the receptor binding domain (RBD). The antibodies termed herein BLN1, BLN2, BLN3, BLN4, BLN5, BLN6, BLN7, BLN8, BLN9, BLN10, BLN12, BLN14 are directed to the N-terminal domain (NTD). These antibodies were capable of binding to SARS Cov-2 and neutralize it, as demonstrated by the plaque reduction neutralization assay presented below.

The antibodies of the present invention can be used inter alia as a therapy for COVID-19 patients.

Therefore, in a first of its aspects, the present invention provides an isolated monoclonal antibody or antigen-binding fragment thereof which binds to Severe acute respiratory syndrome coronavirus 2 (SARS Cov-2) spike protein. In particular, the present invention provides an isolated monoclonal antibody or antigen-binding fragment thereof which binds to the receptor binding domain (RBD) of the SARS Cov-2 spike protein, or an isolated monoclonal antibody or antigen-binding fragment thereof which binds to the N-terminal domain (NTD) of the SARS Cov-2 spike protein.

The term "SARS Cov-2 (also referred to herein as "Severe acute respiratory syndrome coronavirus 2") spike protein" refers to the surface protein of SARS Cov-2 (or the 2019 novel coronavirus (2019-nCoV) as previously termed by the World Health Organization (WHO)). SARS Cov-2 is the RNA virus that causes the disease termed COVID-19.

Coronaviruses contain four structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, of which the spike (S) protein plays the most important role in viral attachment, fusion and cell entry. The S protein mediates viral entry into host cells by first binding to a host receptor through the receptor-binding domain (RBD) in the S1 subunit and then fusing the viral and host membranes through the S2 subunit. SARS-CoV-2 recognizes angiotensin-converting enzyme 2 (ACE2) as its host receptor.

The receptor-binding domain (RBD) of the spike protein as known in the art is defined as the region located between amino acids 318-542 of the spike protein (GenPept:QHD43416 ORF) and responsible for attachment to the ACE2 receptor.

The S1 subunit of the spike protein as known in the art is defined as the region located between amino acids 1-1207 of the spike protein (GenPept:QHD43416 ORF).

The N-terminal domain (NTD) of the S1 subunit is located between amino acids 1-305 of the Spike protein (GenPept:QHD43416 ORF). The function of the NTD is not well understood but it was suggested to play a role in mediating prefusion to post-fusion transition of the S protein and may also bind specific sugar moieties on the surface of cells, accommodating an alternative route for virus cell entry.

Specifically, the present invention provides an isolated monoclonal antibody or antigen-binding fragment thereof which binds to Severe acute respiratory syndrome coronavirus 2 (SARS Cov-2) spike protein, wherein said antibody comprises: a. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 33, CDRH2 denoted by SEQ ID NO. 34, CDRH3 denoted by SEQ ID NO. 35, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 36, a CDRL2 denoted by SEQ ID NO. 37, and a CDRL3 denoted by SEQ ID NO. 38; or b. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 39, CDRH2 denoted by SEQ ID NO. 40, CDRH3 denoted by SEQ ID NO. 41, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 42, a CDRL2 denoted by SEQ ID NO. 43, and a CDRL3 denoted by SEQ ID NO. 44; or c. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 45, CDRH2 denoted by SEQ ID NO. 46, CDRH3 denoted by SEQ ID NO. 47, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 48, a CDRL2 denoted by SEQ ID NO. 49, and a CDRL3 denoted by SEQ ID NO. 50; or d. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 51, CDRH2 denoted by SEQ ID NO. 52, CDRH3 denoted by SEQ ID NO. 53, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 54, a CDRL2 denoted by SEQ ID NO. 55, and a CDRL3 denoted by SEQ ID NO. 56; or e. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 57, CDRH2 denoted by SEQ ID NO. 58, CDRH3 denoted by SEQ ID NO. 59, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 60, a CDRL2 denoted by SEQ ID NO. 61, and a CDRL3 denoted by SEQ ID NO. 62; or f. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 63, CDRH2 denoted by SEQ ID NO. 64, CDRH3 denoted by SEQ ID NO. 65, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 66, a CDRL2 denoted by SEQ ID NO. 67, and a CDRL3 denoted by SEQ ID NO. 68; or g. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 69, CDRH2 denoted by SEQ ID NO. 70, CDRH3 denoted by SEQ ID NO. 71, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 72, a CDRL2 denoted by SEQ ID NO. 73, and a CDRL3 denoted by SEQ ID NO. 74; or h. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 75, CDRH2 denoted by SEQ ID NO. 76, CDRH3 denoted by SEQ ID NO. 77, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 78, a CDRL2 denoted by SEQ ID NO. 79, and a CDRL3 denoted by SEQ ID NO. 80 i. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 201, CDRH2 denoted by SEQ ID NO. 202, CDRH3 denoted by SEQ ID NO. 203, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 204, a CDRL2 denoted by SEQ ID NO. 205, and a CDRL3 denoted by SEQ ID NO. 206; or j. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 207, CDRH2 denoted by SEQ ID NO. 208, CDRH3 denoted by SEQ ID NO. 209, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 210, a CDRL2 denoted by SEQ ID NO. 211, and a CDRL3 denoted by SEQ ID NO. 212; or k. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 213, CDRH2 denoted by SEQ ID NO. 214, CDRH3 denoted by SEQ ID NO. 215, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 216, a CDRL2 denoted by SEQ ID NO. 217, and a CDRL3 denoted by SEQ ID NO. 218; or l. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 219, CDRH2 denoted by SEQ ID NO. 220, CDRH3 denoted by SEQ ID NO. 221, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 222, a CDRL2 denoted by SEQ ID NO. 223, and a CDRL3 denoted by SEQ ID NO. 224; or m. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 225, CDRH2 denoted by SEQ ID NO. 226, CDRH3 denoted by SEQ ID NO. 227, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 228, a CDRL2 denoted by SEQ ID NO. 229, and a CDRL3 denoted by SEQ ID NO. 230; or n. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 231, CDRH2 denoted by SEQ ID NO. 232, CDRH3 denoted by SEQ ID NO. 233, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 234, a CDRL2 denoted by SEQ ID NO. 235, and a CDRL3 denoted by SEQ ID NO. 236; or o. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 237, CDRH2 denoted by SEQ ID NO. 238, CDRH3 denoted by SEQ ID NO. 239, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 240, a CDRL2 denoted by SEQ ID NO. 241, and a CDRL3 denoted by SEQ ID NO. 242; or p. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 243, CDRH2 denoted by SEQ ID NO. 244, CDRH3 denoted by SEQ ID NO. 245, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 246, a CDRL2 denoted by SEQ ID NO. 247, and a CDRL3 denoted by SEQ ID NO. 248; or q. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 249, CDRH2 denoted by SEQ ID NO. 250, CDRH3 denoted by SEQ ID NO. 251, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 252, a CDRL2 denoted by SEQ ID NO. 253, and a CDRL3 denoted by SEQ ID NO. 254; or r. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 255, CDRH2 denoted by SEQ ID NO. 256, CDRH3 denoted by SEQ ID NO. 257, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 258, a CDRL2 denoted by SEQ ID NO. 259, and a CDRL3 denoted by SEQ ID NO. 260; or s. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 261, CDRH2 denoted by SEQ ID NO. 262, CDRH3 denoted by SEQ ID NO. 263, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 264, a CDRL2 denoted by SEQ ID NO. 265, and a CDRL3 denoted by SEQ ID NO. 266; or t. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 267, CDRH2 denoted by SEQ ID NO. 268, CDRH3 denoted by SEQ ID NO. 269, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 270, a CDRL2 denoted by SEQ ID NO. 271, and a CDRL3 denoted by SEQ ID NO. 272; or u. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 273, CDRH2 denoted by SEQ ID NO. 274, CDRH3 denoted by SEQ ID NO. 275, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 276, a CDRL2 denoted by SEQ ID NO. 277, and a CDRL3 denoted by SEQ ID NO. 278; or v. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 279, CDRH2 denoted by SEQ ID NO. 280, CDRH3 denoted by SEQ ID NO. 281, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 282, a CDRL2 denoted by SEQ ID NO. 283, and a CDRL3 denoted by SEQ ID NO. 284; or w. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 285, CDRH2 denoted by SEQ ID NO. 286, CDRH3 denoted by SEQ ID NO. 287, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 288, a CDRL2 denoted by SEQ ID NO. 289, and a CDRL3 denoted by SEQ ID NO. 290; or x. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 291, CDRH2 denoted by SEQ ID NO. 292, CDRH3 denoted by SEQ ID NO. 293, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 294, a CDRL2 denoted by SEQ ID NO. 295, and a CDRL3 denoted by SEQ ID NO. 296; or y. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 297, CDRH2 denoted by SEQ ID NO. 298, CDRH3 denoted by SEQ ID NO. 299, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 300, a CDRL2 denoted by SEQ ID NO. 301, and a CDRL3 denoted by SEQ ID NO. 302; or z. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 303, CDRH2 denoted by SEQ ID NO. 304, CDRH3 denoted by SEQ ID NO. 305, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 306, a CDRL2 denoted by SEQ ID NO. 307, and a CDRL3 denoted by SEQ ID NO. 308.

As indicated below, antibodies MD17 and MD29 possess the highest affinity toward the S1 protein (K of 2 nM) followed by antibodies MD47, MD65 and MD67 (K D D of 5-12 nM) and antibodies MD45 and MD63 (K of 38 nM and 47 nM, respectively).

D Therefore in some embodiments the isolated monoclonal antibody or antigen-binding fragment thereof according to the present invention is wherein said antibody or antigen- binding fragment thereof binds the S1 subunit of the spike protein with a K of about 1 D pM to about 100 nM.

In other embodiments the isolated monoclonal antibody or antigen-binding fragment thereof according to the present invention is wherein said antibody or antigen- binding fragment thereof binds the S1 subunit of the spike protein with a K of about 1 D nM to about 100 nM.

Determination of the dissociation constant K is well known to those of skill in D the art and may be performed for examples as described below.

As indicated above, the present invention provides isolated monoclonal antibodies that bind to SARS Cov-2 spike protein. The term “antibody” refers to a polypeptide encoded by an immunoglobulin gene that specifically binds and recognizes an antigen, in the present case SARS Cov-2 spike protein.

The term “monoclonal antibody”, “monoclonal antibodies” or “mAb” as herein defined refers to a population of substantially homogenous antibodies, i.e., the individual antibodies comprising the population are identical except for possibly naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are directed against a single antigenic site (epitope).

Monoclonal antibodies may be prepared and purified by any method known in the art. For example, monoclonal antibodies may be prepared from B cells taken from the spleen or lymph nodes of immunized animals (e.g. rabbits, rats, mice or monkeys), or isolated from the blood of recovered COVID 19 patients that were shown in serological tests to contain antibodies directed to SARS Cov2 spike protein.

Based on the results obtained from a phage display library, full length antibodies are produced, as known in the art, and as described below.

Purification of monoclonal antibodies may be performed using any method known in the art, for example by affinity chromatography, namely, by using an affinity column to which a specific epitope (or antigen) is conjugated. Alternatively, purification of antibodies may be based on using protein A and protein G column chromatography, as described below.

An exemplary antibody structural unit comprises a tetramer, as known in the art.

Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one “light chain” and one “heavy chain”. The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen (or epitope) recognition.

Thus, the terms “heavy chain variable region” (V ) and “light chain variable H region” (V ) refer to these heavy and light chains, respectively. More specifically, the L variable region is subdivided into hypervariable and framework (FR) regions.

Hypervariable regions have a high ratio of different amino acids in a given position, relative to the most common amino acid in that position. Four FR regions which have more stable amino acids sequences separate the hypervariable regions. The hypervariable regions directly contact a portion of the antigen's surface. For this reason, hypervariable regions are herein referred to as "complementarity determining regions", or "CDRs", the CDRs are positioned either at the heavy chain of the antibody (a "heavy chain complementarity determining region") or at the light chain of the antibody (a "light chain complementarity determining region").

From N-terminal to C-terminal, both light and heavy chains comprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the CDR is located.

Thus, the complementarity determining regions CDRH1, CDRH2 and CDRH3 refer to the three complementarity determining regions starting from the N-terminus of the antibody’s heavy chain (also referred to herein as heavy chain complementarity determining region) and the complementarity determining regions CDRL1, CDRL2 and CDRL3 refer to the three complementarity determining regions starting from the N- terminus of the antibody’s light chain (also referred to herein as light chain complementarity determining region).

The present invention encompasses antigen-binding fragments of the isolated anti SARS Cov2 spike protein monoclonal antibody of the invention.

As used herein the term "antigen binding fragment" relates to a fragment of the full length antibody which retains the antibody's specificity of binding to SARS Cov2 spike protein. An antigen binding fragment encompasses but is not limited to Fv, single chain Fv (scFv), single chain Fv-Fc (scFv-Fc), Fab’, Fab, F(ab’) and F(ab) . 2 2 Such fragments may be produced by any method known in the art, for example by proteolytic cleavage, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab') fragments). 2 Thus in some embodiments the antibody according to the invention is wherein said antibody is an antibody fragment selected from the group consisting of a single-chain Fv-Fc (scFv-Fc) molecule, single chain Fv (scFv), Fv, Fab’, Fab, F(ab’) , F(ab) and any 2 2 combination thereof.

In some specific embodiments, the antibody or antigen-binding fragment thereof is a single chain variable fragment-Fc fragment (scFv-Fc) molecule. In other specific embodiments, the antibody or antigen-binding fragment thereof is a single chain variable fragment (scFv) molecule.

In specific embodiments the isolated monoclonal antibody of the invention or the antigen-binding fragment thereof binds to the spike protein. In certain embodiments the isolated monoclonal antibody or antigen-binding fragment thereof according the present invention is wherein said antibody or antigen-binding fragment thereof binds to at least one of the Receptor binding domain (RBD), the S1 subunit, or the N-terminal domain (NTD) of the spike protein. In further specific embodiments the isolated monoclonal antibody of the invention or the antigen-binding fragment thereof binds to the receptor binding domain of the spike protein.

As demonstrated in Example 4 below, binding of the antibodies of the invention inhibited the ability of SARS-CoV-2 virus to infect VERO-E6 culture. Therefore, in certain embodiments the isolated monoclonal antibodies of the invention or the antigen- binding fragment thereof inhibits the ability of SARS-CoV-2 virus to infect VERO-E6 culture cells.

By the term “inhibit” in the context of the present invention it is meant that the isolated monoclonal antibody of the invention or the antigen-binding fragment thereof impedes, hinders, prohibits or suppresses by at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or about 100% of the ability of SARS-CoV-2 virus to infect VERO-E6 culture cells as compared to SARS-CoV-2 virus infection in the absence of the antibody of the invention or the antigen-binding fragment thereof.

The term “cell” or “cells” as referred to herein is used at its broadest sense.

In some embodiments the isolated anti SARS Cov2 spike protein monoclonal antibody is a chimeric antibody, a human antibody, or a humanized antibody.

The term "human antibody" as used herein refers to an antibody that possesses an amino acid sequence corresponding to that of an antibody produced by a human and/or has been made using any of the techniques for making human antibodies known in the art. This definition specifically excludes a humanized antibody that comprises non-human antigen-binding residues.

Preparation of humanized and human antibodies is well known in the art.

Antibodies may also be prepared using phage display. As known in the art, antibody phage display (APD) is based on genetic engineering of bacteriophages and repeated rounds of antigen-guided selection and phage propagation.

The APD process begins with antibody-library preparation (e.g. as described in the Examples section below), by preparation of quality RNA from the cell source chosen (e.g., lymph nodes and blood samples). This RNA is reverse transcribed into cDNA, which is used for PCR of the VH and VL chains of the encoded antibodies. This step is followed by ligation of the variable heavy (VH) and variable light (VL) PCR products into a phage display vector, culminating in analysis of clones of mAbs.

For preparing large quantities of the antibody (either chimeric, humanized or human), a stable cell line expressing the antibody can be prepared, by transfecting cells (e.g. CHO cells) with the Ig expression vector containing both heavy and light chains of the antibody. The antibodies may then be manufactured for example in a state of the art single-use bioreactor system. The antibodies may be purified to clinical grade using well established monoclonal antibody purification methods. Highly anti- SARS Cov2 spike protein antibody producing clones may then be selected and expanded based on antibody levels in the supernatant, as tested by any method known in the art, for example, a SARS Cov2 spike protein -specific ELISA assay, as detailed herein below. A master cell bank, developed for the specific clone, may serve as the starting growing material for all clinical grade batches.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 33, a CDRH2 denoted by SEQ ID NO. 34, a CDRH3 denoted by SEQ ID NO. 35, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 36, a CDRL2 denoted by SEQ ID NO. 37, and a CDRL3 denoted by SEQ ID NO. 38.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 39, a CDRH2 denoted by SEQ ID NO. 40, a CDRH3 denoted by SEQ ID NO. 41, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 42, a CDRL2 denoted by SEQ ID NO. 43, and a CDRL3 denoted by SEQ ID NO. 44.

In other embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 45, a CDRH2 denoted by SEQ ID NO. 46, a CDRH3 denoted by SEQ ID NO. 47, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 48, a CDRL2 denoted by SEQ ID NO. 49, and a CDRL3 denoted by SEQ ID NO. 50.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 51, a CDRH2 denoted by SEQ ID NO. 52, a CDRH3 denoted by SEQ ID NO. 53, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 54, a CDRL2 denoted by SEQ ID NO. 55, and a CDRL3 denoted by SEQ ID NO. 56.

In other embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 57, a CDRH2 denoted by SEQ ID NO. 58, a CDRH3 denoted by SEQ ID NO. 59, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 60, a CDRL2 denoted by SEQ ID NO. 61, and a CDRL3 denoted by SEQ ID NO. 62.

In various embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 63, a CDRH2 denoted by SEQ ID NO. 64, a CDRH3 denoted by SEQ ID NO. 65, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 66, a CDRL2 denoted by SEQ ID NO. 67, and a CDRL3 denoted by SEQ ID NO. 68.

In certain embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 69, a CDRH2 denoted by SEQ ID NO. 70, a CDRH3 denoted by SEQ ID NO. 71, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 72, a CDRL2 denoted by SEQ ID NO. 73, and a CDRL3 denoted by SEQ ID NO. 74.

In other embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 75, a CDRH2 denoted by SEQ ID NO. 76, a CDRH3 denoted by SEQ ID NO. 77, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 78, a CDRL2 denoted by SEQ ID NO. 79, and a CDRL3 denoted by SEQ ID NO. 80.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 1 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 2.

In other embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 3 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 4.

In some further embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 5 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 6.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 7 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 8.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 9 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 10.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 11 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 12.

In other embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 13 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 14.

In certain embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 15 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by SEQ ID NO. 16. In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 17 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 18, or a variant thereof.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by any one of SEQ ID NOs. 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137 or 139 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70%, or 75%, or 80%, or 85%, or 90% or more identical to the nucleic acid sequence denoted by any one of SEQ ID NOs. 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138 or 140.

In other embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 19 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. , or a variant thereof.

In some further embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 21 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 22, or a variant thereof.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 23 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 24, or a variant thereof.

In certain embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 25 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 26, or a variant thereof.

In some embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 27 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 28, or a variant thereof.

In other embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 29 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. , or a variant thereof.

In various embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 31 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 32, or a variant thereof.

In other embodiments, the present invention provides an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence denoted by any one of SEQ ID NOs. 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by any one of SEQ ID NOs. 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, or a variant thereof.

In other embodiments the isolated antibody according to the invention is wherein said antibody is an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody comprises six CDR sequences as denoted by SEQ ID Nos. 33-38, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 17 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 18.

In other embodiments the isolated antibody according to the invention is wherein said antibody is an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody comprises six CDR sequences as denoted by SEQ ID Nos. 39-44, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO:19 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 20.

In further embodiments the isolated antibody according to the invention is wherein said antibody is an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody comprises six CDR sequences as denoted by SEQ ID Nos. 45-50, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 21 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 22.

In various embodiments the isolated antibody according to the invention is wherein said antibody is an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody comprises six CDR sequences as denoted by SEQ ID Nos. 51-56, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 23 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 24.

In other embodiments the isolated antibody according to the invention is wherein said antibody is an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody comprises six CDR sequences as denoted by SEQ ID Nos. 57-62, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 25 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 26.

In further embodiments the isolated antibody according to the invention is wherein said antibody is an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody comprises six CDR sequences as denoted by SEQ ID Nos. 63-68, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 27 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 28.

In other embodiments the isolated antibody according to the invention is wherein said antibody is an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody comprises six CDR sequences as denoted by SEQ ID Nos 69-74, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 29 and a light chain variable region comprising an amino acid sequence having at least 90% sequence homology to SEQ ID NO. 30.

In various other embodiments the isolated antibody according to the invention is wherein said antibody is an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody comprises six CDR sequences as denoted by SEQ ID Nos. 75-80, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence homology to SEQ ID NO. 31 and a light chain variable region comprising an amino acid sequence having at least 90% sequence homology to SEQ ID NO. 32.

In other embodiments the isolated antibody according to the invention is wherein said antibody is an anti SARS Cov2 spike protein isolated monoclonal antibody or antigen-binding fragment thereof, wherein said antibody comprises six CDR sequences as denoted by the SEQ ID Nos. listed in Table 8 or Table 9, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to the SEQ ID NOs. listed in Table 6 or Table 7 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to the SEQ ID NOs. listed in Table 6 or Table 7.

As detailed above, in specific embodiments the isolated antibody according to the invention is an scFv-Fc antibody, namely an antibody comprising a single chain variable fragment comprising both the heavy and light chain CDRs fused to an Fc fragment.

In one specific embodiment the isolated antibody according to the invention is an scFv-Fc antibody comprising six CDR sequences as denoted by SEQ ID Nos. 33-38, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 17 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 18.

In another specific embodiment the isolated antibody according to the invention is an scFv-Fc antibody comprising six CDR sequences as denoted by SEQ ID Nos. 39- 44, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 19 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 20.

In one specific embodiment the isolated antibody according to the invention is an scFv-Fc antibody comprising six CDR sequences as denoted by SEQ ID Nos. 45-50, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 21 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 22.

In another specific embodiment the isolated antibody according to the invention is an scFv-Fc antibody comprising six CDR sequences as denoted by SEQ ID Nos. 51- 56, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 23 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 24.

In a further specific embodiment the isolated antibody according to the invention is an scFv-Fc antibody comprising six CDR sequences as denoted by SEQ ID Nos. 57- 62, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 25 and a light chain variable region having at least 90% sequence homology to SEQ ID NO. 26.

In another specific embodiment the isolated antibody according to the invention is an scFv-Fc antibody comprising six CDR sequences as denoted by SEQ ID Nos. 63- 68, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 27 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 28.

In one further specific embodiment the isolated antibody according to the invention is an scFv-Fc antibody comprising six CDR sequences as denoted by SEQ ID Nos. 69-74, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 29 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO.

. In a certain embodiment the isolated antibody according to the invention is an scFv-Fc antibody comprising six CDR sequences as denoted by SEQ ID Nos. 75-80, and a heavy chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 31 and a light chain variable region comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO. 32.

In another embodiment, the present invention provides an isolated monoclonal antibody that binds the same epitope as an antibody comprising: (a) a heavy chain CDR1 comprising SEQ ID NO. 33, a heavy chain CDR2 comprising SEQ ID NO. 34, and a heavy chain CDR3 comprising SEQ ID NO. 35; and a light chain CDR1 comprising SEQ ID NO. 36, a light chain CDR2 comprising SEQ ID NO. 37, and a light chain CDR3 comprising SEQ ID NO. 38; or (b) a heavy chain CDR1 comprising SEQ ID NO. 39, a heavy chain CDR2 comprising SEQ ID NO. 40, and a heavy chain CDR3 comprising SEQ ID NO. 41; and a light chain CDR1 comprising SEQ ID NO. 42, a light chain CDR2 comprising SEQ ID NO. 43, and a light chain CDR3 comprising SEQ ID NO. 44; or (c) a heavy chain CDR1 comprising SEQ ID NO. 45, a heavy chain CDR2 comprising SEQ ID NO. 46, and a heavy chain CDR3 comprising SEQ ID NO. 47; and a light chain CDR1 comprising SEQ ID NO. 48, a light chain CDR2 comprising SEQ ID NO. 49, and a light chain CDR3 comprising SEQ ID NO. 50; or (d) a heavy chain CDR1 comprising SEQ ID NO. 51, a heavy chain CDR2 comprising SEQ ID NO. 52, and a heavy chain CDR3 comprising SEQ ID NO. 53; and a light chain CDR1 comprising SEQ ID NO. 54, a light chain CDR2 comprising SEQ ID NO. 55, and a light chain CDR3 comprising SEQ ID NO. 56; or (e) a heavy chain CDR1 comprising SEQ ID NO. 57, a heavy chain CDR2 comprising SEQ ID NO. 58, and a heavy chain CDR3 comprising SEQ ID NO. 59; and a light chain CDR1 comprising SEQ ID NO. 60, a light chain CDR2 comprising SEQ ID NO. 61, and a light chain CDR3 comprising SEQ ID NO. 62; or (f) a heavy chain CDR1 comprising SEQ ID NO. 63, a heavy chain CDR2 comprising SEQ ID NO. 64, and a heavy chain CDR3 comprising SEQ ID NO. 65; and a light chain CDR1 comprising SEQ ID NO. 66, a light chain CDR2 comprising SEQ ID NO. 67, and a light chain CDR3 comprising SEQ ID NO. 68; or (g) a heavy chain CDR1 comprising SEQ ID NO. 69, a heavy chain CDR2 comprising SEQ ID NO. 70, and a heavy chain CDR3 comprising SEQ ID NO. 71; and a light chain CDR1 comprising SEQ ID NO. 72, a light chain CDR2 comprising SEQ ID NO. 73, and a light chain CDR3 comprising SEQ ID NO. 74; or (h) a heavy chain CDR1 comprising SEQ ID NO. 75, a heavy chain CDR2 comprising SEQ ID NO. 76, and a heavy chain CDR3 comprising SEQ ID NO. 77; and a light chain CDR1 comprising SEQ ID NO. 78, a light chain CDR2 comprising SEQ ID NO. 79, and a light chain CDR3 comprising SEQ ID NO. 80.

The nucleic acid sequences encoding the heavy and light chains of the antibodies described herein, also termed herein MD17, MD29, MD45, MD47, MD62, MD63, MD65 MD67, BL1, BL2, BL3, BL5, BL6, BL7, BL8, BL9, BL10, BL11, BL12, BLK2, BLK3, BLK10, BLK14, BLK15, BLK21, BLK23 BLN1, BLN2, BLN3, BLN4, BLN5, BLN6, BLN7, BLN8, BLN9, BLN10, BLN12, BLN14 are detailed in Tables 1, 4 and 5 below.

In addition, the amino acid sequences of the heavy and light chains of the antibodies described herein are detailed in Tables 2, 6 and 7 below. Furthermore, the sequences of the CDRs of the above antibodies are displayed in Tables 3, 8 and 9 below.

Table 1: Nucleic acid sequences of the light and heavy chains of the antibodies MD17, MD29, MD45, MD47, MD62, MD63, MD65 and MD67 SEQ ID Sequence Description NO.

GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTCCAGCCGGGGGGGTC MD-17 Heavy chain 1 CCTGAGACTCTCCTGTTCAGCCTCTGGATTCACCTTCAGTACCTATGTTAT nucleic acid GAACTGGGTCCGCCAGGCTCCAGGGAAGGGACTGGAACATGTTTCAGGTA sequence TTAGTAGTGACGGGGGAATCACATACTATGCAGACTCCGTGAAGGGCAGA TTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAGATGAG CAGTCTGAGAGTTGAGGACACGGCTGTGTATTACTGTGTGAAAGATCAGG ATAGTAGCAGCTGGTATGATGCTTTTGATATCTGGGGCCAAGGGACAATG GTCACCGTCTCTTCA GATATTGTGATGACACAGTCTCCATCCTCCCTGTCTGCATCTGTGGGAGAC MD-17 Light chain 2 AGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAACTATTTAAA nucleic acid TTGGTATCAGCAGAAATTAGGGAAAGCCCCTAAGCTCCTGACCTATGCTG sequence CATCCAGATTGCAAAGTGGGGTCCCATCAAGATTCAGTGCCAGTGGATCT GGGACAGAATTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGC GACTTACTACTGTCAACAGAGTTACACTACCCCGCTCACTTTCGGCGGAGG GACCAAGCTGGAGATCAAA CAAATGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC MD-29 Heavy chain 3 CCTGAGACTCTCCTGTTCAGCCTCTGGATTCACCTTCAGTACCTATGTTAT nucleic acid GAACTGGGTCCGCCAGGCTCCAGGGAAGGGACCGGAACATGTTTCAGGTA sequence TTAGTAGTGACGGGGGAATCACATACTATGCGGACTCCGTGAAGGGCAGA TTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAGATGAG CAGTCTGAGAGTTGAGGACACGGCTGTGTATTACTGTGTGAAAGATCAGG ATAGTAGCAGCTGGTATGATGCTTTTGACATCTGGGGCCAAGGGACAATG GTCACCGTCTCTTCA AACATCCGGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGAGAC MD-29 Light chain 4 AGAGTCACCATCACTTGCCGGGCAACTCAGAGCATTAGCAGCTATTTAAA nucleic acid TTGGTATCAGCAGAAACCAGGGAAAGCCCCTAACCTCCTGATCTATGCTG sequence CATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCT GGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCA ACTTACTACTGTCACCAGACTTACACTTCCCCGTACACTTTtgGCCAGGGGA CCAAGCtgGAGATTAAA GAGGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC MD-45 Heavy chain CCTGAGACTCTCCTGTGCAGCCTCTGGGTTCACCGTCAGTAGCAACTACAT nucleic acid GACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTA sequence TTTATAGCGGTGGTAGCACATTCTACGCAGACTCCGTGAAGGGCCGATTC ACCATCTCCAGACACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGCTGAGGACACGGCCGTGTATTACTGTGCGAGAGATTTGTCTG TGCGCGGCGGTATGGACGTCTGGGGTCAAGGGACAATGGTCACCGTCTCT TCA GAAATTGTGTTGACACAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAA MD-45 Light chain 6 AGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAACAGCAGCTACTT nucleic acid AGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATG sequence GTGCATCCAACAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGG TCTGGAACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTT GCAGTGTATTACTGTCAGCAGTATGGTGTCTCACCTGAGATCATCTTCGGC CAAGGGACACGACTGGAGATTAAG CAAATGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTC MD-47 Heavy chain 7 CCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCAT nucleic acid GAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTA sequence TTAGTAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAG CCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGATTTGGTGA CCGCCCCCTCATATGAAGCTTTCGATATCTGGGGCCAAGGGACAATGATC ACCGTCTCTTCA AATTTTATGCTGACTCAGCCACCCTCAGTGTCAGTGGCCCCAGGAAAGAC MD-47 Light chain 8 GGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGTAAAAGTGTGCACT nucleic acid GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCATCTATTATGAT sequence AGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG GAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCC GACTATTACTGTCAGGTGTGGGATAGTAGTAGTCATCATCATGTGGTATTC GGCGGAGGGACGAAGGGGACCGTCCTA GAGGTGCAGCTGGTGCAGTCTGGAGGAGGCTTGATCCAGCCTGGGGGGTC MD-62 Heavy chain 9 CCTGAGACTCTCCTGTGCAGCCTCTGGGGTCACCGTCAGTAGCAACTACAT nucleic acid GACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGAGATCTACAGT ATTACGGTATGGACGTCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCA GCCATCCGGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGAC MD-62 Light chain AGAGTCACCATCACTTGTCGGGCGAGTCAGGATATTGGCAGCTGGTTAGG nucleic acid CTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTG sequence CATCCAGTTTGGCAGGTGGGGTCCCTTCAAGGTTCAGCGGCAGTGGATCT GGGACAGATTTCACTCTCACCATCAGTAGCCTGCAGCCTGAGGATTTTGCA ACTTACTACTGTCAACAGGCTAACAGTTTCCCGCTCACTTTCGGCGGAGGG ACCAAGCTGGAGATCAAA CAGGTCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTC MD-63 Heavy chain 11 CCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTAT nucleic acid GCACTGGGTCCGCCAGGCTCCAGGGAAGGGACTGGAACATGTTTCAGCTA sequence TTAGTAGTGATGGGGGAATCACATACTTTGCAGACTCCGTGAAGGGCAGA TTCACCATCTCCAGAGACAATTCCAGGAACACGCTGTTTCTTCAGATGAGC AGTCTGAGAGTTGAGGACACGGCTGTGTATTACTGTGTGAAAGATCAGGA CAGTAACAGCTGGTATGATGCTTTTGATATCTGGGGCCGAGGGACAATGG TCACCGTCTCTTCA GTCATCTGGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGAC MD-63 Light chain 12 AGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAA nucleic acid TTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTG sequence CATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCT GGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCA ACTTACTACTGTCAACAGAGTTACAGTACCCCGTACACTTTtgGCCAGGGG ACCAAGCtgGAGATCAAA GAAGTGCAACTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC MD-65 Heavy chain 13 CCTGGGACTCTCCTGTGCAGCCTCTGGAGTCACCGTCAGTAGCAACTACAT nucleic acid GAACTGGGTCCGCCAGACTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCAGATTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGATTTAGCAG TGGCTGGCGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTT CA GAAATAGTAATGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGA MD-65 Light chain 14 AAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTATTAGCAGCAGCTACT nucleic acid TAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTAT sequence GGTGCATCCATCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGG GTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATT TCGCAGTGTATTTCTGTCAGCAGTATGGTAGCTCACCTCTCACTTTCGGCG GAGGGACCAAAGTGGAAATCAAA GAAGTGCAACTGGTGGAGTCTGGAGGAGGCTTGGTCCAGCCTGGGGGGTC MD-67 Heavy chain CCTGAGACTCTCCTGTGCAGCCTCTGGGTTCACCGTCAGTAGCAACTACAT nucleic acid GACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTA sequence TTTATAGCGGTGGTAGCACATTCTACGCAGACTCCGTGAAGGGCCGATTC ACCATCTCCAGACACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGCTGAGGACACGGCCGTGTATTACTGTGCGAGAGATTTGTCTG TGCGCGGCGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCC TCA GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAA MD-67 Light chain 16 AGAGCCACCCTCCCCTGCAGGGCCAGTCAGAGTGTTAGTAGCAGCTACTT nucleic acid AGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATG sequence GTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGGG TCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTT GCAGTGTATTACTGTCAGCAGTTTGGTAGCTCACCCCTCACTTTCGGCGGA GGGACCAAAGTGGAAATCAAA Table 2: Amino acid sequences of the light and heavy chains of the antibodies MD17, MD29, MD45, MD47, MD62, MD63, MD65 and MD67 SEQ ID Sequence Description NO.

EVQLLESGGGLVQPGGSLRLSCSASGFTFSTYVMNWVRQAPGKGLEHVSGIS MD-17 Heavy chain 17 SDGGITYYADSVKGRFTISRDNSKNTLYLQMSSLRVEDTAVYYCVKDQDSSS amino acid sequence WYDAFDIWGQGTMVTVSS DIVMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKLGKAPKLLTYAASR MD-17 Light chain 18 LQSGVPSRFSASGSGTEFTLTISSLQPEDFATYYCQQSYTTPLTFGGGTKLEIK amino acid sequence QMQLVQSGGGLVQPGGSLRLSCSASGFTFSTYVMNWVRQAPGKGPEHVSGIS MD-29 Heavy chain 19 SDGGITYYADSVKGRFTISRDNSKNTLYLQMSSLRVEDTAVYYCVKDQDSSS amino acid sequence WYDAFDIWGQGTMVTVSS NIRLTQSPSSLSASVGDRVTITCRATQSISSYLNWYQQKPGKAPNLLIYAASSL MD-29 Light chain QSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQTYTSPYTFGQGTKLEIK amino acid sequence EVQLVQSGGGLVQPGGSLRLSCAASGFTVSSNYMTWVRQAPGKGLEWVSVI MD-45 Heavy chain 21 YSGGSTFYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVYYCARDLSVRG amino acid sequence GMDVWGQGTMVTVSS EIVLTQSPGTLSLSPGERATLSCRASQSVNSSYLAWYQQKPGQAPRLLIYGAS MD-45 Light chain 22 NRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGVSPEIIFGQGTRLEI amino acid sequence K QMQLVQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAI MD-47 Heavy chain 23 SSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDLVTAP amino acid sequence SYEAFDIWGQGTMITVSS NFMLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSD MD-47 Light chain 24 RPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSHHHVVFGGGTK amino acid sequence GTVL EVQLVQSGGGLIQPGGSLRLSCAASGVTVSSNYMTWVRQAPGKGLEWVSLIY MD-62 Heavy chain SGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLQYYG amino acid sequence MDVWGQGTMVTVSS AIRMTQSPSSVSASVGDRVTITCRASQDIGSWLGWYQQKPGKAPKLLIYAASS MD-62 Light chain 26 LAGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKLEIK amino acid sequence QVTLKESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEHVSAIS MD-63 Heavy chain 27 SDGGITYFADSVKGRFTISRDNSRNTLFLQMSSLRVEDTAVYYCVKDQDSNS amino acid sequence WYDAFDIWGRGTMVTVSS VIWLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSL MD-63 Light chain 28 QSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK amino acid sequence EVQLVESGGGLVQPGGSLGLSCAASGVTVSSNYMNWVRQTPGKGLEWVSVI MD-65 Heavy chain 29 YSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLAVA amino acid sequence GAFDIWGQGTMVTVSS EIVMTQSPGTLSLSPGERATLSCRASQSISSSYLAWYQQKPGQAPRLLIYGASI MD-65 Light chain RATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYFCQQYGSSPLTFGGGTKVEIK amino acid sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMTWVRQAPGKGLEWVSVI MD-67 Heavy chain 31 YSGGSTFYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVYYCARDLSVRG amino acid sequence GMDVWGQGTTVTVSS EIVLTQSPGTLSLSPGERATLPCRASQSVSSSYLAWYQQKPGQAPRLLIYGASS MD-67 Light chain 32 RATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQFGSSPLTFGGGTKVEIK amino acid sequence Table 3: CDR amino acid sequences of the antibodies MD17, MD29, MD45, MD47, MD62, MD63, MD65 and MD67 SEQ Sequence Description ID NO.

STYVMN 33 MD-17 Heavy chain CDR H1 GISSDGGITYYADSVKG 34 MD-17 Heavy chain CDR H2 DQDSSSWYDAFDI MD-17 Heavy chain CDR H3 RASQSISNYLN 36 MD-17 Light chain CDR L1 AASRLQS 37 MD-17 Light chain CDR L2 QQSYTTPLTFGG 38 MD-17 Light chain CDR L3 STYVMN 39 MD-29 Heavy chain CDR H1 GISSDGGITYYADSVK 40 MD-29 Heavy chain CDR H2 DQDSSSWYDAFDI 41 MD-29 Heavy chain CDR H3 RATQSISSYLN 42 MD-29 Light chain CDR L1 AASSLQS 43 MD-29 Light chain CDR L2 HQTYTSPYTFGQ 44 MD-29 Light chain CDR L3 SSNYMT 45 MD-45 Heavy chain CDR H1 VIYSGGSTFYADSVKG 46 MD-45 Heavy chain CDR H2 DLSVRGGMDV 47 MD-45 Heavy chain CDR H3 RASQSVNSSYLA 48 MD-45 Light chain CDR L1 GASNRAT 49 MD-45 Light chain CDR L2 QQYGVSPEIIFGQ 50 MD-45 Light chain CDR L3 SSYAMS 51 MD-47 Heavy chain CDR H1 AISSGGSTYYADSVKG 52 MD-47 Heavy chain CDR H2 DLVTAPSYEAFDI 53 MD-47 Heavy chain CDR H3 GGNNIGSKSVH 54 MD-47 Light chain CDR L1 YDSDRPS 55 MD-47 Light chain CDR L2 QVWDSSSHHHVVFGG 56 MD-47 Light chain CDR L3 AASGVTVSSNYMT 57 MD-62 Heavy chain CDR H1 LIYSGGSTYYADSVKG 58 MD-62 Heavy chain CDR H2 DLQYYGMDV 59 MD-62 Heavy chain CDR H3 RASQDIGSWLG 60 MD-62 Light chain CDR L1 AASSLAG 61 MD-62 Light chain CDR L2 QQANSFPLTFGG 62 MD-62 Light chain CDR L3 AASGFTFSSYAMH 63 MD-63 Heavy chain CDR H1 AISSDGGITYFADSVKG 64 MD-63 Heavy chain CDR H2 DQDSNSWYDAFDI 65 MD-63 Heavy chain CDR H3 RASQSISSYLN 66 MD-63 Light chain CDR L1 AASSLQS 67 MD-63 Light chain CDR L2 QQSYSTPYTFGQ 68 MD-63 Light chain CDR L3 AASGVTVSSNYMN 69 MD-65 Heavy chain CDR H1 VIYSGGSTYYADSVKG 70 MD-65 Heavy chain CDR H2 DLAVAGAFDI 71 MD-65 Heavy chain CDR H3 RASQSISSSYLA 72 MD-65 Light chain CDR L1 GASIRAT 73 MD-65 Light chain CDR L2 QQYGSSPLTFGG 74 MD-65 Light chain CDR L3 CAASGFTVSSNYMT 75 MD-67 Heavy chain CDR H1 VIYSGGSTFYADSVKG 76 MD-67 Heavy chain CDR H2 DLSVRGGMDV 77 MD-67 Heavy chain CDR H3 RASQSVSSSYLA 78 MD-67 Light chain CDR L1 GASSRAT 79 MD-67 Light chain CDR L2 QQFGSSPLTFGG 80 MD-67 Light chain CDR L3 Table 4: Nucleic acid sequences of the light and heavy chains of the anti-RBD SARS-Cov-2 antibodies SEQ ID Sequence Description NO.

GAGGTGCAGCTGGTGGAGACTGGGGGAGGCTTGGTACAGCCTGGCAGATC BL1 Heavy chain 81 CCTGAGACTCTCCTGTGCAGCCTCTGGATTCATCTTTGATGATTATGCCAT nucleic acid GCACTGGGTCCGGCAAGCTCCAGGGAAGGGCCTGGAGTGGGTCTCAGGTA sequence TTAGTTGGAATAGTGGTAGCATAGGCTATGCGGTCTCTGTGAAGGGCCGA TTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAA CAGTCTGAGAGCTGAGGACACGGCCTTGTATTACTGTGCAAAAGCCCCAC TAGGAGAGCTGCTACCCGGCGACTGGTTCGACCCCTGGGGCCAGGGAACC CTGGTCACTGTCTCCTCA GCCCTGACTCAGCCTCCCTCCGCGTCCGGGTCTCCTGGACAGTCAGTCACC BL1 Light chain 82 ATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGCTTTTAACTATGTCTCC nucleic acid TGGTACCAACATCACCCCGGCAAAGCCCCCAAACTCTTGATTTATGACGTC sequence ACTAAGCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAAGTCTGGC AACACGGCCTCCCTGACCGTCTCTGGGCTCCTGGCTGAGGATGAGGCTGA TTATTATTGTGCCTCATATGCGGGCAGCAACAATTTTGTCTTCGGAACTGG GACCAAGGTGACCGTCCTA CAGGTCCAGCTGGTGCAATCTGGGGGACGTGTGGTACGGCCTGGGGTGCC BL2 Heavy chain 83 CCTGAGACTCTCCTGTGCAGCCTCTGGATTCATCTTTGATGATTATGCCAT nucleic acid GCACTGGGTCCGGCAAGCTCCAGGGAAGGGCCTGGAGTGGGTCTCAGGTA sequence TTAGTTGGAATAGTGGTAGCATAGGCTATGCGGTCTCTGTGAAGGGCCGA TTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAA CAGTCTGAGAGCTGAGGACACGGCCTTGTATTACTGTGCAAAAGCCCCAC TAGGAGAGCTGCTACCCGGCGACTGGTTCGACCCCTGGGGCCAGGGAACC CTGGTCACCGTCTCCTCA CTGCCTGGGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAG BL2 Light chain 84 GGTCACCATCTCTTGTTCTGGAAGCAGGTCCAACATCGGAAATAACTATGT nucleic acid ATCCTGGTACCAGCAACTCCCAGGAACGGCCCCCAAACCCATCATCTTTA sequence GTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGT CTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCAGTCTGAGGATGAG GCTGATTATTACTGTGCAGCATGGGATGACAGCCTGAATGGTTGGGTGTTC GGCGGAGGGACGAAGGTCACCGTCCTA GAGGTACAGCTGGTGGAGTCCGGGGGAGGCTTGGTACAGCCTGGCAGGTC BL3 Heavy chain 85 CCTGAGACTCTCCTGTGAAGTCTCTGGATTCACCTTTGAGGACTATGACAT nucleic acid GCAGTGGGTCCGGCAAGCTCCAGGGAAGGGCCTAGAGTGGGTCTCAGGTA sequence TTAGTTGGAATGGTGGTATCATAGGCTATGGGGACTCCGTGAAGGGCCGA TTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAA CAGTCTGAGAGGTGAGGACACGGCCTTATATTCCTGTGCAAAAGCCCTCC ATAGTGGCGACGATTCCGGCCAGCAGGCTTTTGATATCTGGGGCCAAGGG ACAATGGTCACCGTCTCTTCA CTGGCTGTGCTGACTCAGCCACCCTCGGTGTCGGTGGCCCCAGGAAAGAC BL3 Light chain 86 GGCCAGGATTACCTGTGGGGGAAACAACATTGGAGCGAAAAGTGTACACT nucleic acid GGTACCAGCAGAGGCCAGGCCAGGCCCCTGTCCTGGTCGTCTTTGATGAC sequence AGCGACCGGCCCCCAGGGATCCCTGAGCGATTCTCTGGCTCCAAGTCTGG GAACACGGCCACCCTGACCATCAGCAGAGTCGAAGCCGGGGATGAGGCC GACTATTACTGTCAAGTGTGGGATAGTAGTAGTGATCATGTGATATTCGGC GGAGGGACCAAGGTGACCGTCCTA GAAGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC BL5 Heavy chain 87 CCTGAGACTCTCCTGTGCAGCCTCTGGACTCACCGTCAGTAGGAACTACAT nucleic acid GAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAA CCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGTAG TTTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA CAGTCTGTCTTGACTCAGCCACCCTCAGTGTCAGTGACCCCAGGAAAGAC BL5 Light chain 88 GGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGTAAAAGTGTGCACT nucleic acid GGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCATCTATTATGAT sequence AGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGG GAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCC GACTATTACTGTCAGGTGTGGGATAGTAGTAGTGATCATGTGGTATTCGGC GGAGGGACCGAGCTGACCGTCCTA GAGGTACAACTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGCAGGTC BL6 Heavy chain 89 CCTGAGACTCTCCTGTGAAGTCTCTGGATTCACCTTTGAGGACTATGACAT nucleic acid GCAGTGGGTCCGGCAAGCTCCAGGGAAGGGCCTAGAGTGGGTCTCAGGTA sequence TTAGTTGGAATGGTGGTATCATAGGCTATGGGGACTCCGTGAAGGGCCGA TTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAA CAGTCTGAGAGGTGAGGACACGGCCTTATATTCCTGTGCAAAAGCCCTCC ATAGTGGCGACGATTCCGGCCAGCAGGCTTTTGATATCTGGGGCCAAGGG ACAATGGTCACCGTCTCTTCA TCCTATGTGCTGACACAGCCACCCTCGGTGTCAGTGGCCCCAGGACAGAC BL6 Light chain 90 GGCCAAGATTACCTGTGGCGAAAACAACATTGGGCGTAGAAGTGTACACT nucleic acid GGTACCAACAGAAGCCAGGCCAGGCCCCTGTGTTGGTCATCTTCAATGAT sequence AGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGGTCCATGTCTGG GAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCC GACTATTACTGTCAGGTGTGGGATAGTGGCAGTGATCATGTGGTATTCGG CGGAGGGACGGAGCTGACCGTCCTA CAGGTGCAGCTGCAGGAGTCGGGGGGAGGCTTGGTACAGCCTGGGGGGT BL7 Heavy chain 91 CCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTACCTATAGCA nucleic acid TGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGCAGTGGGTTTCATAC sequence ATTAGTAGTAGTGGTAATACCATGTACTACGCAGACTCTGTGAAGGGCCG ATTCACCATCTCCAGAGACAATGCCAAGAACTCACTGTATCTGCAAATGA ACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGATCAT GGAATTGGCTATGAGACGGAAGGGCCAGACTACTGGGGCCAGGGAACCC TGGTCACCGTCTCCTCA CAGTCTGTGTTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAG BL7 Light chain 92 GGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACATCGGAAGTAATTATGT nucleic acid ATACTGGTACCAGCAGCTCCCCGGAACGGCCCCCAAACTCCTCATCTATA sequence GGAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAG TCTGGCACCTCAGCCTCCCTGgCCATCAGTGGGCTCCGGTCCGAGGATGAG GCTGATTATTACTGTGCAGCATGGGATGACAGCCTGAGTGGTGTGGTATTC GGCGGAGGGACCGAGCTGACCGTCCTA CAGGTTCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTC BL8 Heavy chain 93 GGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCTCCTTCAGCAGCTATACTAT nucleic acid CAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAAGG sequence ATCATCCCTATCCTTGGCATAGCAAACTACGCACAGAAGTTCCAGGGCAG AGTCACGATTACCGCGGACAAATCCACGAGCACAGCCTACATGGAGCTGA GCAGCCTGAGATCTGAGGACACGACCGTGTATTACTGTGCGAGAGACCGG GGGTATAGCAGCTCTGGAAGTAACTACTACATGGACGTCTGGGGCAAAGG GACAATGGTCACCGTCTCTTCA CAGTCTGTGTTGACGCAGCCGCCCTCAATATCTGCGGCCCCTGGACAGAA BL8 Light chain 94 GGTCACCATCTCCTGCACTGGGAGCAGCTCCAACATCGGGGCAGGTTATG nucleic acid ATGTACACTGGTACCAGCAGCTTCCAGGAACAGCCCCCAAACTCCTCATC sequence TATGGTAACAGCAATCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCC AAGTCTGGCACCTCAGCCTCCCTGGCCATCACTGRGCTCCAGGCTGAGGA TGAGGCTGATTATTACTGCCAGTCCTATGACAGCAGCCTGAGTGGTTCGG GGGTGTTCGGCGGAGGGACCAAGGTGACCGTCCTA GAAGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC BL9 Heavy chain 95 CCTGAGACTCTCCTGTGTAGCCTCCGGATTCACCGTCAGTAGCAACTACAT nucleic acid GAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAACTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGGATCTTCAAATGAACAG CCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGGGGATGGTT CGGACAACTACTACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTC ACCGTCTCCTCA CAGTCTGTGTTGACTCAGCCACCCTCAGTGTCTGCGGCCCCAGGGCAGAG BL9 Light chain 96 GGTCACCCTCTCCTGCACTGGGAACAGCTCCAACATCGGGGCAGGTTATG nucleic acid ATGTACACTGGTACCAACAGCTTCCAGGAGCAGCCCCCAAACTCCTCATTT sequence ATGGTAACACCAATCGCCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCA AGTCTGGCACCTCAGCCTCCCTGGCCATCACTGGGCTCCAGGCTGAGGAT GAGGCTGATTATTACTGTGCAGCATGGGATGACAGCCTGAGTGGTCTATT CGGCGGAGGGACCGAGCTGACCGTCCTA CAGGTTCAGCTTGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTC BL10 Heavy chain 97 AGTGAAGGTCTCCTGCAAGGTTTCCGGATACACCCTCACTGAATTATCCAT nucleic acid GCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGTT sequence TTGATCCTGAAGATGCTGAAACGATCTACGCACAGAAGTTCCAGGGCAGA GTCACCATGACCGAGGACACATCTACAGACACAGCCTACATGGAGCTGAG CAGCCTGAGATCTGAGGACACGGCCGTGTATTATTGTGTAACAGCGCCCG TTATAACTGGAAGTCCCGAGGCTTACTCCTACTACTACGGTATGGATGTCT GGGGCCAAGGGACCACGGTCACCGTCTCCTCA TCTTATGAGCTGACTCAGCCTCGCTCAATCTCCGGGTCTCCTGGGCAGTCA BL10 Light chain 98 GTCGCCATCTCCTGCACTGGAACCAACAATGATATTGGGGGTTATAACCTT nucleic acid GTCTCCTGGTACCAACAACACCCCGGCAAAGTCCCCAAGCTCATGATTTAT sequence GAAGTCGATCAGCGGCCCTCAGGGGTCTCTGATCGCTTCTCGGGCTCCAA GTCTGGCGACACGGCCTCCCTGACAATCTCTGGGCTCCAGACTGACGACG AGGCTGATTATTACTGCAGCTCATATACAAGCACCAACACTCACGTATTCG GCGGAGGGACCAAGGTCACCGTCCTA CAGGTACAGCTGCAGCAGTCAGGGGCTGAGGTGAAGAAGCCTGGGGCCT BL11 Heavy chain 99 CGGTGAAGGTCTCCTGCAAGGTTTCCGGATACACCCTCACTGAATTATCCA nucleic acid TGCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGT sequence TTTGATCCTGAAGATGCTGAAACAATCTACGCACAGAAGTTCCAGGGCAG AGTCACCATGACCGAGGACGCATCTACAGACACAGCCTACATGGAGCTGA GCAGCCTGAGATCTGAGGACACGGCCGTGTATTATTGTGTAACAGCGCCC GTTATAACTGGAAGTCCCGAGGCTTACTCCTACTACTACGGTATGGATGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA TCTTCTGTGCTGACTCAGCCTCGCTCAGTGTCCGGGACTCCTGGACAGTCA BL11 Light chain 100 GTCACCATCTCCTGCACTGGAACCAGCAGTGATGTGGGTGGTTATAATTAT nucleic acid GTCTCCTGGTACCAACAACACCCAGGCAAAGTCCCCAAACTCATGATTTA sequence TGAGGTCAGTAAGCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAA GTCTGGCAACACGGCCTCCCTGAGCATCTCTGGGCTCCAGGCTGAGGACG AGGCTGATTATTACTGCAGCTCATATACAATCAGCAGCACTTATGTCTTCG GAACTGGGACGAAGGTGACCGTCCTA CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTC BL12 Heavy chain 101 AGTGAAGGTCTCCTGCAAGGTTTCCGGATACACCCTCCCTGAATTATCCAT nucleic acid GCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGTT sequence TTGATCCTGAAGATGGTGAAACAATCTACGCACAGAAGTTCCAGGGCAGA GTCACCATGACCGAGGACACATTGACAGACACAGCCTACATGGAGCTGAG CAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCAACAGGACCCG CTATAGCAGCAGCTGCCACTGGGTGGTTCGACCCCTGGGGCCAGGGAACC CTGGTCACCGTCTCCTCA CAGTCTGCCCTGACTCAGCCTCGCTCAGTGTCCGGGTCTCTTGGACAGTCA BL12 Light chain 102 GTCACCATCTCCTGCGCTGGAACCAGCAGTGACGTTGGTAGTTATAATCGT nucleic acid GTCTCTTGGTACCAGCAGACCCCAGGCACGGCCCCCAAACTCATGATTTAT sequence GAAGTCAGTAATCGGCCCTCAGGGGTCTCTGATCGCTTCTCTGGGTCCAAG TCTGGCGACACGGCCTCCCTGACAATCTCTGGGCTCCAGGCTGAGGACGA GGCTGATTATTACTGCAGTTCATATTCCAGCAGCAGCACTGTGGTTTTCGG CGGAGGGACCAAGGTCACCGTCCTA GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCGGGGGGGTC BLK2 Heavy chain 103 CCTGAGACTCTCCTGTGCAGCCTCTGGACTCACCGTCAGTAGGAACTACAT nucleic acid GAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGGCTCCGTGAAGGGCCGATTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGTAG TTTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA GTCATCCGGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGAC BLK2 Light chain 104 AGAGTCACCATCACTTGCCAGGCGAGTCAGGACATTAACAAGTATTTAAA nucleic acid TTGGTATCAACAGAAACCAGGGAAAGCCCCTAAGCTCCTAATCTACGATG sequence CATCCAATTTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCT GGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATATTGG AACATATTACTGTCAACAGTATGATAATGTCCCTCCTAGTTTTGGCCAGGG GACCAAGGTGGAAATCAAAA CAGGTGCAGCTTGTACAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC BLK3 Heavy chain 105 CCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCGTCAGTAGGAACTACAT nucleic acid GAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAATTA sequence TTTATAGCGGTGGTAGCACATTCTACGCAGACTCCGTGAAGGGCAGATTC ACCATCTCCAGAGACAATTCCAAGAACACTCTGTATCTTCAAATGAACAG CCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGATG TAGTGGGGGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCC TCA GAAATAGTATTGACACAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGA BLK3 Light chain 106 GAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCGGCAGCTACT nucleic acid TAGCCTGGTACCAGCAGAAACCTGGCCTGGCGCCCATGCTCCTCATCTATG sequence ATGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGCG TCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTT GCAGTGTATTACTGTCAGCAGTATGGTAGCTCATCGTGGACGTTCGGCCA AGGGACCAAGGTGGAAATCAAA CAGGTGCAGCTGCAGGAGTCGGGGGGAGGCTTGGTCCAGCCTGGGGGGTC BLK10 Heavy chain 107 CCTGAGACTCTCCTGTGCAGCCTCTGGAGTCACCGTCAGTAGCAACTACAT nucleic acid GAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCAGATTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGTCGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGCCG GGGAATGGGGTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCT TCA GACATCGTGATGACCCAGACTCCATCCTCCCTGTCTGCATCTGTAGGAGAC BLK10 Light chain 108 AGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATGTAAA nucleic acid TTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTG sequence CATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCT GGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCA ACTTACTACTGTCAACAGACTTACATTACCCCGTACAGTTTTGGCCAGGGG ACCAAGCTGGAGATCAAA CAGGTTCAGCTGGTACAATCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC BLK14 Heavy chain 109 CCTGAGACTCTCCTGTGCAGCCTCTGGACTCACCGTCAGTAGGAACTACAT nucleic acid GAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGTAG TTTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA GAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAA BLK14 Light chain 110 AGAGCTACCCTCTCCTGTAGGGCCAGTCATGATATTGGTGGGTACGTTGCC nucleic acid TGGTACCAACAGAGGCCTGGCCAGGCTCCCAGGCTCCTCATCTATGATAC sequence ATCCAGTAGGGCCACTGGCATCGCAGACAGGTTCAGTGGCAGTGGGTCTG GGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGCA GTGTATTACTGTCAGCAATATGGTACCTCACCTCTCACTTTCGGCGGAGGG ACCAAAGTGGAGATCAAA CAGGTTCAGCTGGTGCAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC BLK15 Heavy chain 111 CCTGAGACTCTCCTGTGCAGCCTCTGGACTCACCGTCAGTAGGAACTACAT nucleic acid GAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGTAG TTTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA GAAATTGTGTTGACGCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAA BLK15 Light chain 112 AGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAACTACTTAGC nucleic acid CTGGTACCAACAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTATGCTG sequence CATCCAGCAGGGCCACTGGCACCCCAGACAGGTTCAGTGGCAGTGGGTCT GGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATTTTGC AGTGTATTACTGTCAGCAGTATGGTAGCTCACCGCTCACTTTCGGCGGAGG GACACGACTGGAGATTAAA GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC BLK21 Heavy chain 113 CCTGAGACTCTCCTGTGCAGCCTCTGGACTCACCGTCAGTAGGAACTACAT nucleic acid GAGCTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAGTGGGTCTCACTTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGTAG TTTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA GCCATCCGGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGAC BLK21 Light chain 114 AGAGTCACCATCACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAA nucleic acid TTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTG sequence CATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCT GGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGC AACTTACTACTGTCAACAGAGTGACAGCAGCCCGCTCACTTTCGGCGGTG GGACCAAGCTGGAGATCAAA CAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTC BLK23 Heavy chain 115 CCTGAGACTCTCCTGTGCAGCCTCTGGACTCACCGTCAGTAGGAACTACAT nucleic acid GAGCTGGGTCCGCCGGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCACTTA sequence TTTATAGCGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGATTC ACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAG CCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTGGTAG TTTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA GTCATCCGGTTGACCCAGTCTCCATCTTTCCTGTCTGCATCTGTAGGAGAC BLK23 Light chain 116 AGAGTCACCATCACTTGCCGGGCCAGTCAGGGCATTAGCAATTATTTAGC nucleic acid CTGGTATCAGCAAAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATTCTG sequence CATCCACTTTGCAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCT GGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGATTTTGC AACTTATTACTGCCAACAACTAAATAGTTACCCTCTCACTTTCGGCGGAGG GACACGACTGGAGATTAAA Table 5: Nucleic acid sequences of the light and heavy chains of the anti-NTD SARS-Cov-2 antibodies SEQ ID Sequence Description NO.

GAAGTGCAGCTGGTACAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTC BLN1 Heavy chain 117 AGTGAAGGTCTCCTGCAAGGTTTCCGGATACACCCTCACTGAATTATCCAT nucleic acid GCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGTT sequence TTGATCCTGAAGATGCTGAAACAATCTACGCACAGAAGTTCCAGGGCAGA GTCACCATGACCGAGGACACATCTACAGACACAGCCGAGATGGAGCTGA GCAGCCTGAGATCTGAGGACACGGCCGTGTATTATTGTGTAACAGCGCCC GCTATAACTGGAAGTCCCGAGGCTTACTCCTACTACTACAGTGTGGATGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA GATATTGTGATGACTCAGACTCCACTCTCCTCACCCGTCACCCTTGGACAG BLN1 Light chain 118 CCGGCCTCCATCTCCTGCAGGTCTAGTCAAAGCCTAGTACACAGTGACGG nucleic acid AAACACTTACTTGAGTTGGCTTCAGCAGAGGCCAGGCCAGCCTCCCAGAC sequence TCCTAATTCATAAGACTTCTAACCGGTTCTTTGGGGTCCCAGAGAGATTCA GTGGCAGTGGGGCAGGGACAGATTTCACACTGAAAATCAGCAGGGTGGA AGCTGAGGATGTCGGGGTTTATTACTGCCTGCAAGCTACACAATTTCCGTA CACTTTTGGCCAGGGGACCAAGCTGGAGATCAAA GAAGTGCAGCTGGTACAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTC BLN2 Heavy chain 119 AGTGAAGGTCTCCTGCAAGGTTTCCGGATACACCCTCACTGAATTATCCAT nucleic acid GCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGTT sequence TTGATCCTGAAGATGGTGAAACAATCTACGCACAGAAGTTCCAGGGCAGA GTCACCATGACCGAGGACACATCTACAGACACAGCCTACATGGAGCTGAG CAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCAGCAAGCCCCG CGGTTCGGGGGTCCCCTTCAAACTTCTACTACTACCACGGTATGGACGTCT GGGGCCAAGGGACAATGGTCACCGTCTCTTCA CAGTCTGTCGTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCG BLN2 Light chain 120 ATCACCATCTCCTGCACTGGATCCAGCAGTGACATTGGTGGTTATAACTAT nucleic acid GTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTTT sequence GAGGGCAGTAAGCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAA GTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACG AGGCTGATTATTACTGCAGCTCATATACAAGCAGCAGCACTCTCGTATTCG GCGGAGGGACCGAGCTGACCGTCCTA CAGGTACAGCTGCAGCAGTCAGGGGCTGAGGTGAAGAAGCCTGGGGCCT BLN3 Heavy chain 121 CAGTGAGGGTCTCCTGCAAGGTTTCCGGATACACCCTCACTGAATTATCCA nucleic acid TGCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGT sequence TTTGATCCTGAAGATGCTGAAACAATCTACGCACAGAAGTTCCAGGGCAG AGTCACCATGACCGAGGACACATCTACAGACAGAGCCTACATGGAGCTGA GCAGCCTGAGATCTGAGGACACGGCCGTGTATTATTGTGTAGCAGCGCCC GTTATAACTGGAAGTCCCGAGGCTTACTCCTACTACTACGGTATGGATGTC TGGGGCCAAGGGACCACGGTCACCGTCTCCTCA CAGTCTGCCCTGACTCAGCCTGCCTCCTTGTCTGGGTCTCCTGGACAGTCG BLN3 Light chain 122 ATCACCATCTCCTGCACTGGAACCAGCAGTGATGTTGGGAGTTATAACCTT nucleic acid GTCTCCTGGTACCAACAGCACCCAGGCAAAACCCCCAAAGTCATTATTTA sequence TGAGGTCACCAATCGGGCCTCAGGGGTTTCTAATCGCTTCTCTGGCTCCCA GTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACG AGGCTGATTATTACTGCAGCTCATATACACGCACCAGCACTCTCGATGTGG TATTCGGCGGAGGGACAGAGCTAACCGTTCTA CAGCTGCAGCTGCAGGAGTCCGGCCCAGGACTGGTGAAGCCTTCACAGAC BLN4 Heavy chain 123 CCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGTAGTGGTAGTTA nucleic acid CTACTGGAGCTGGATCCGGCAGCCCGCCGGGAAGGGACTGGAGTGGATTG sequence GGCGTATCTATACCACTGGGAGCACCAGCTACAACCCCTCCCTCAAGAGT CGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCT GAGCTCTGTGACCGCCGCAGACACGGCCGTGTATTACTGTGCGAGAATGG CCTATCAGGTGTATTACTATGATAGTAGTGGTTATTACGATGCTTTTGATA TCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCA AATTTTATGCTGACTCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAG BLN4 Light chain 124 GGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACATCGGAAGTAATACTGT nucleic acid AAACTGGTACCAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATA sequence GTAAAAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAG TCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCGGTCCGAGGATGA GGCTGATTATTACTGTTCAGCATGGGATGACAGCCTGCGTGGTTATGTCTT CGGACCTGGGACCAAGGTCACCGTCCTA CAGGTGCAACTGCAGGAGTCAGGGGCTGAGGTGAAGAAGCTGGGGCTCA BLN5 Heavy chain 125 GTGAAGGTCTCTGCAAGGTTTCCGGATACACCCTCACTGAATTATCCATGC nucleic acid ACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGTTTT sequence GATCCTGAAGATGCTGAAACAATCTACGCACAGAAGTTCCAGGGCAGAGT CACCATGACCGAGGACACATCTACAGACACAGCCTACATGGAGCTGAGCA GCCTGAGATCTGAGGACACGGCCGTGTATTATTGTGTAACAGCGCCCGTT ATAACTGGAAGTCCCGAGGCTTACTCCTACTACTACGGTATGGATGTCTGG GGCCAAGGGACCACGGTCACCGTCTCCTCA CAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGCCCCCTGGACAGTCG BLN5 Light chain 126 ATCACTATCTCCTGCACTGGAACCAGCAGTGATATTGGTGGTTATAACCTT nucleic acid GTCTCCTGGTACCAACAGCACCCAGGCAAAGCCCCCAAACTCATGATTTA sequence TGAGGGCACTAAGCGGCCCTCAGGGGTTTCTTATCGCTTCTCTGGCTCCAA GTCTGGCAACACGGCCTCCCTGACAATATCGGGGCTCCAGGCTGAGGACG AGGCTGATTATTACTGTTCCTCATATGCAGGTAGTCCCACCCTTTGGGTGT TCGGCGGAGGGACCAAGGTGACCGTCCTA CAGGTGCAACTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGAC BLN6 Heavy chain 127 CCTGTCCCTCACCTGCACTGTCTCTGGTGGCTCCATCAGCAGTGGTAGTTA nucleic acid TTACTGGAGCTGGATCCGGCAGCCCGCCGGGAAGGGACTGGAGTGGATTG sequence GGCGCATCTATACCACTGGGAGCACCAACTACAACCCCTCCCTCAAGAGT CGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCT GAGCTCTGTGACCGCCGCAGACACGGCCGTGTATTACTGTGCGAGAATGG CCTATCAGGTGTATTACTATGATAGTAGTGGTTATTACGATGCTTTTGATA TCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCA CAGTCTGCCCTGACTCAGCCTGCCTCCGCGTCCGGGTCTCCTGGACAGTCA BLN6 Light chain 128 GTCACCATCTCCTGCACTGGAAGCAGCAGTGACGTTGGTGGTTATAACTTT nucleic acid GTCTCCTGGTACCAACAACACCCCGGCAAAGCCCCCAAACTCATCATTTAT sequence GAGGTCAGTAAGCGGCCCTCAGGGGTCCCTAATCGCTTCTCTGGCTCCAA GTCCGGCAACACGGCCTCCCTCACCGTCTCTGGGCTCCAGGCTGACGATG AGGCTCTTTATTACTGCAGCTCATATGCAGGCAGCAACAATTATGTCTTCG GACCTGGGACCAAGGTCACCGTCCTA GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTC BLN7 Heavy chain 129 AGTGAAGGTCTCCTGCAAGGTTTCCGGATACACCCTCCCTGAATTATCCAT nucleic acid GCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGTT sequence TTGATCCTGAAGATGGTGGAACAATCTACGCACAGAAGTTCCAGGGCAGA GTCACCATGACCGAGGACACATCTACAGACACAGCCTACATGGAGCTGAG CAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCAACCTCTCGGG TGGCTGGTACACCCAACTGGTTCCACCCCTGGGGCCAGGGAACCCTGGTC ACTGTCTCCTCA CAGTCTGTGTTGACGCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCG BLN7 Light chain 130 ATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTAT nucleic acid GTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATTTA sequence TGATGTCAGTAATCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAA GTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACG AGGCTGATTATTACTGCAGCTCATATACAAGCAGCAGCACTCTTGTCTTCG GAACTGGGACCAAGGTCACCGTCCTA GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTC BLN8 Heavy chain 131 CCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTAT nucleic acid GCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGCAGTGGGTGGCACTTA sequence TATCATATGATGGGAGTAATAAATACTACGCAGACTCCGTGAAGGGCCGA TTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAA CAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCTTG GCAGTGGCTGGTACCCCTGGGGCCAGGGAACCCTGGTCACTGTCTCCTCA AATTTTATGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACA BLN8 Light chain 132 GCCAGCATCACCTGCTCTGGAGATAAATTGGGGGATAAATATGCTTCTTG nucleic acid GTACCAGCAGAAGCCAGGCCAGTCCCCTGTGCTGGTCATCTATCAAGATA sequence GCAAGCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGG AACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGGCTGA CTATTACTGTCAGGCGTGGGACAGCAGCACGGTGGTATTCGGCGGAGGGA CGGAGCTGACCGTCCTA CAGGTGCAGCTTGTACAATCTGGGGCTGGGGTGAAGAAGCCTGGGGCCTC BLN9 Heavy chain 133 AGTGAAGGTCTCCTGCAAGGTTTCCGGATACACCCTCCCTGAATTATCCAT nucleic acid GCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGTT sequence TTGATCCTGAAGATGGTGAAACAATCTACGCACAGAAGTTCCAGGGCAGA GTCACCATGACCGAGGACACATCTACAGACACAGCCTACATGGAGCTGAG CAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCAACCTCTCGGG TGGCTGGTACACCCAACTGGTTCCACCCCTGGGGCCAGGGAACCCTGGTC ACCGTCTCCTCA CAGTCTGCCCTGACTCAGCCTGTCTCCGTGTCTGGGTCTCCTGGACAGTCG BLN9 Light chain 134 ATCACCATCTCCTGCACTGGAACCAGCAGTGACGTTGGTCGTTATAACTAT nucleic acid GTCTCCTGGTACCAACAACACCCAGGAAAAGCCCCCAAACTCATTATTTA sequence TGATGTGAAGAATCGGCCCTCAGGGGTCCCTGATCGCTTCTCTGGCTCCAA GTCTGGCAACACGGCCTCCCTGACCATCTCTGGGCTCCAGGCTGAGGACG AGGCTGATTATTACTGCAGCTCATATACAAGGAGCAGCACTCTCGATGTG GTATTCGGCGGAGGGACGGAGCTGACCGTCTTA CAGGTGCAGCTGGTACAATCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTC BLN10 Heavy chain 135 AGTGAAGGTCTCCTGCAAGGTTTCCGGATACACCCTCCCTGAATTATCCAT nucleic acid GCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGTT sequence TTGATCCTGAAGATGGTGAAACAATCTACGCACAGAAGTTCCAGGGCAGA GTCACCATGACCGAGGACACATCGACAGACACAGCCTACATGGAGCTGAG CAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCAACAGGACCCG CTATAGCAGCAGCTGCCACTGGGTGGTTCGACCCCTGGGGCCAGGGAACC CTGGTCACCGTCTCCTCA TCCTATGAGCTGATTCAGGAGCCCTCAGTGTCCGTGTCCCCAGGACAGAC BLN10 Light chain 136 AGCCAGGATCACATGCCAAGGAGACAGCCTCAGAAGCTATTATGCAAGCT nucleic acid GGTACCAGCAGAAGCCAGGGCAGGCCCCTGTTCTTGTCATCTACAATAGA sequence AACAAGCGGCCCTCAGGGATCCCAGACCGATTCTCTGGCTCCAGCTCAGG AAACACAGCTTCCTTGACCATCACTGGGGCTCAGGCGGATGATGAGGCTG ACTATTACTGTAACTCCCGGGACAACAGTGGTAACCATCCCTTCGGCGGA GGGACCAAGGTCACCGTCCTA CAGGTACAGCTGCAGCAGTCAGGGGCTGAGGTGAAGAAGCcTGGGGCCTC BLN12 Heavy chain 137 AGTGAAGGTCTCcTGCAAGGTTTCCGGATACACCCTCACTGAATTATCCAT nucleic acid GCACTGGGTGCGACAGGCTCCTGGAAAAGGGCTTGAGTGGATGGGAGGTT sequence TTGATCCTGAAGATGCTGAAACAATCTACGCACAGAAGTTCCAGGGCAGA GTCACCATGACCGAGGACACATCTACAGACACAGCCTACATGGAGCTGAG CAGCCTGAGATCTGAGGACACGGCCGTGTATTATTGTGTAACAGCGCCCG TTATAACTGGAAGTCCCGAGGCTTACTCCTACTACTACGGTATGGATGTCT GGGGCCAAGGGACCACGGTCAACGTCTCCTCA GACATTGTGATGACTCAGTCTCCACTCTCCTCACCTGTCACCCTTGGACAG BLN12 Light chain 138 CCGGCCTCCATCTCCTGCAGGTCTAGTCAAAGCCTCGTACACAGTGATGG nucleic acid AAACACCTACTTGAGTTGGCTTCAGCAGAGGCCAGGCCAGCCTCCAAGAC sequence TCCTAATTTATAAGATTTCTAACCGGTTCTCTGGGGTCCCAGACAGATTCA GTGGCAGTGGGGCAGGGACAGATTTCACACTGAAAATCAGCAGGGTGGA AGCTGAGGATGTCGGGGTTTATTACTGCATGCAAGCTACACAATTTCCCAT CACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA CAAATGCAGCTGGTGCAGTCTGGGGGAGGCGTGGTCCAGcCTGGGAGGTC BLN14 Heavy chain 139 CCTGAGACTCTCCTGTGCAGCCTCTGGATCCACCTTCAGTAGCTATGGCAT nucleic acid GCACTGGGTCCGCCAGGCTCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTA sequence TATCATTTGATGGAAGTAATAAATTCTATGCAGACTCCGTGAAGGGCCGA TTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAA CAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGATCATG ACGATGGATACTACTTCTACTACTACATGGACGTCTGGGGCAAAGGGACC ACGGTCACCGTCTCCTCA GAAATAGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGA BLN14 Light chain 140 AAGAGCCACCCTCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACT nucleic acid TAGCCTGGTACCAGCAGAAACCTGGCCAGGCTCCCAGGCTCCTCATCTAT sequence GGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTTCAGTGGCAGTGG GTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGATT TTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACGGACTTTCGGCGGAG GGACACGACTGGAGATTAAA Table 6: Amino acid sequences of the light and heavy chains of the anti-RBD SARS-Cov-2 antibodies SEQ ID Sequence Description NO.

EVQLVETGGGLVQPGRSLRLSCAASGFIFDDYAMHWVRQAPGKGLEWVSGI BL1 Heavy chain 141 SWNSGSIGYAVSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKAPLGE amino acid sequence LLPGDWFDPWGQGTLVTVSS ALTQPPSASGSPGQSVTISCTGTSSDVGAFNYVSWYQHHPGKAPKLLIYDVTK BLN1 Light chain 142 RPSGVPDRFSGSKSGNTASLTVSGLLAEDEADYYCASYAGSNNFVFGTGTKV amino acid sequence TVL QVQLVQSGGRVVRPGVPLRLSCAASGFIFDDYAMHWVRQAPGKGLEWVSGI BL2 Heavy chain 143 SWNSGSIGYAVSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKAPLGE amino acid sequence LLPGDWFDPWGQGTLVTVSS LPGLTQPPSASGTPGQRVTISCSGSRSNIGNNYVSWYQQLPGTAPKPIIFSNNQ BL2 Light chain 144 RPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGWVFGGGTK amino acid sequence VTVL EVQLVESGGGLVQPGRSLRLSCEVSGFTFEDYDMQWVRQAPGKGLEWVSGI BL3 Heavy chain 145 SWNGGIIGYGDSVKGRFTISRDNAKNSLYLQMNSLRGEDTALYSCAKALHSG amino acid sequence DDSGQQAFDIWGQGTMVTVSS LAVLTQPPSVSVAPGKTARITCGGNNIGAKSVHWYQQRPGQAPVLVVFDDSD BL3 Light chain 146 RPPGIPERFSGSKSGNTATLTISRVEAGDEADYYCQVWDSSSDHVIFGGGTKV amino acid sequence TVL EVQLVESGGGLVQPGGSLRLSCAASGLTVSRNYMSWVRQAPGKGLEWVSLI BL5 Heavy chain 147 YSGGSTYYADSVKGRFTISRDNSKNTLYLQMNNLRAEDTAVYYCARDLVVY amino acid sequence GMDVWGQGTTVTVSS QSVLTQPPSVSVTPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSD BL5 Light chain 148 RPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTEL amino acid sequence TVL EVQLVESGGGLVQPGRSLRLSCEVSGFTFEDYDMQWVRQAPGKGLEWVSGI BL6 Heavy chain 149 SWNGGIIGYGDSVKGRFTISRDNAKNSLYLQMNSLRGEDTALYSCAKALHSG amino acid sequence DDSGQQAFDIWGQGTMVTVSS SYVLTQPPSVSVAPGQTAKITCGENNIGRRSVHWYQQKPGQAPVLVIFNDSDR BL6 Light chain 150 PSGIPERFSGSMSGNTATLTISRVEAGDEADYYCQVWDSGSDHVVFGGGTEL amino acid sequence TVL QVQLQESGGGLVQPGGSLRLSCAASGFTFSTYSMNWVRQAPGKGLQWVSYI BL7 Heavy chain 151 SSSGNTMYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDHGI amino acid sequence GYETEGPDYWGQGTLVTVSS QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYRNN BL7 Light chain 152 QRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGVVFGGGT amino acid sequence ELTVL QVQLVQSGAEVKKPGSSVKVSCKASGGSFSSYTISWVRQAPGQGLEWMGRII BL8 Heavy chain 153 PILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTTVYYCARDRGYSSS amino acid sequence GSNYYMDVWGKGTMVTVSS QSVLTQPPSISAAPGQKVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNS BL8 Light chain 154 NRPSGVPDRFSGSKSGTSASLAITXLQAEDEADYYCQSYDSSLSGSGVFGGGT amino acid sequence KVTVL EVQLVQSGGGLVQPGGSLRLSCVASGFTVSSNYMSWVRQAPGKGLEWVSTI BL9 Heavy chain 155 YSGGSTYYADSVKGRFTISRDNSKNTLDLQMNSLRAEDTAVYYCARGDGSD amino acid sequence NYYYGMDVWGQGTTVTVSS QSVLTQPPSVSAAPGQRVTLSCTGNSSNIGAGYDVHWYQQLPGAAPKLLIYG BL9 Light chain 156 NTNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCAAWDDSLSGLFGGG amino acid sequence TELTVL QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGG BL10 Heavy chain 157 FDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCVTAPVIT amino acid sequence GSPEAYSYYYGMDVWGQGTTVTVSS SYELTQPRSISGSPGQSVAISCTGTNNDIGGYNLVSWYQQHPGKVPKLMIYEV BL10 Light chain 158 DQRPSGVSDRFSGSKSGDTASLTISGLQTDDEADYYCSSYTSTNTHVFGGGTK amino acid sequence VTVL QVQLQQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGG BL11 Heavy chain 159 FDPEDAETIYAQKFQGRVTMTEDASTDTAYMELSSLRSEDTAVYYCVTAPVI amino acid sequence TGSPEAYSYYYGMDVWGQGTTVTVSS SSVLTQPRSVSGTPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKVPKLMIYE BL11 Light chain 160 VSKRPSGVPDRFSGSKSGNTASLSISGLQAEDEADYYCSSYTISSTYVFGTGTK amino acid sequence VTVL QVQLVQSGAEVKKPGASVKVSCKVSGYTLPELSMHWVRQAPGKGLEWMGG BL12 Heavy chain 161 FDPEDGETIYAQKFQGRVTMTEDTLTDTAYMELSSLRSEDTAVYYCATGPAI amino acid sequence AAAATGWFDPWGQGTLVTVSS QSALTQPRSVSGSLGQSVTISCAGTSSDVGSYNRVSWYQQTPGTAPKLMIYEV BL12 Light chain 162 SNRPSGVSDRFSGSKSGDTASLTISGLQAEDEADYYCSSYSSSSTVVFGGGTK amino acid sequence VTVL EVQLVESGGGLVQPGGSLRLSCAASGLTVSRNYMSWVRQAPGKGLEWVSLI BLK2 Heavy chain 163 YSGGSTYYAGSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLVVY amino acid sequence GMDVWGQGTTVTVSS VIRLTQSPSSLSASVGDRVTITCQASQDINKYLNWYQQKPGKAPKLLIYDASN BLK2 Light chain 164 LETGVPSRFSGSGSGTDFTFTISSLQPEDIGTYYCQQYDNVPPSFGQGTKVEIK amino acid sequence QVQLVQSGGGLVQPGGSLRLSCAASGFTVSRNYMSWVRQAPGKGLEWVSII BLK3 Heavy chain 165 YSGGSTFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLDVV amino acid sequence GGMDVWGQGTTVTVSS EIVLTQSPGTLSLSPGERATLSCRASQSVSGSYLAWYQQKPGLAPMLLIYDAS BLK3 Light chain 166 SRATGIPDRFSGSASGTDFTLTISRLEPEDFAVYYCQQYGSSSWTFGQGTKVEI amino acid sequence K QVQLQESGGGLVQPGGSLRLSCAASGVTVSSNYMSWVRQAPGKGLEWVSVI BLK10 Heavy chain 167 YSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRVEDTAVYYCARDLAGE amino acid sequence WGFDIWGQGTMVTVSS DIVMTQTPSSLSASVGDRVTITCRASQSISSYVNWYQQKPGKAPKLLIYAASSL BLK10 Light chain 168 QSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYITPYSFGQGTKLEIK amino acid sequence QVQLVQSGGGLVQPGGSLRLSCAASGLTVSRNYMSWVRQAPGKGLEWVSLI BLK14 Heavy chain 169 YSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLVVY amino acid sequence GMDVWGQGTTVTVSS EIVLTQSPATLSLSPGERATLSCRASHDIGGYVAWYQQRPGQAPRLLIYDTSSR BLK14 Light chain 170 ATGIADRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGTSPLTFGGGTKVEIK amino acid sequence QVQLVQSGGGLVQPGGSLRLSCAASGLTVSRNYMSWVRQAPGKGLEWVSLI BLK15 Heavy chain 171 YSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLVVY amino acid sequence GMDVWGQGTTVTVSS EIVLTQSPATLSLSPGERATLSCRASQSVSNYLAWYQQKPGQAPRLLIYAASS BLK15 Light chain 172 RATGTPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTRLEIK amino acid sequence EVQLVESGGGLVQPGGSLRLSCAASGLTVSRNYMSWVRQAPGRGLEWVSLI BLK21 Heavy chain 173 YSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLVVY amino acid sequence GMDVWGQGTTVTVSS AIRLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSL BLK21 Light chain 174 QSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSDSSPLTFGGGTKLEIK amino acid sequence QVQLVESGGGLVQPGGSLRLSCAASGLTVSRNYMSWVRRAPGKGLEWVSLI BLK23 Heavy chain 175 YSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLVVY amino acid sequence GMDVWGQGTTVTVSS VIRLTQSPSFLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYSASTL BLK23 Light chain 176 QSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPLTFGGGTRLEIK amino acid sequence Table 7: Amino acid sequences of the light and heavy chains of the anti-NTD SARS-Cov-2 antibodies SEQ ID Sequence Description NO.

EVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGG BLN1 Heavy chain 177 FDPEDAETIYAQKFQGRVTMTEDTSTDTAEMELSSLRSEDTAVYYCVTAPAIT amino acid sequence GSPEAYSYYYSVDVWGQGTTVTVSS DIVMTQTPLSSPVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPGQPPRLLIH BLN1 Light chain 178 KTSNRFFGVPERFSGSGAGTDFTLKISRVEAEDVGVYYCLQATQFPYTFGQGT amino acid sequence KLEIK EVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGG BLN2 Heavy chain 179 FDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCAASPAV amino acid sequence RGSPSNFYYYHGMDVWGQGTMVTVSS QSVVTQPASVSGSPGQSITISCTGSSSDIGGYNYVSWYQQHPGKAPKLMIFEGS BLN2 Light chain 180 KRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTLVFGGGTELT amino acid sequence VL QVQLQQSGAEVKKPGASVRVSCKVSGYTLTELSMHWVRQAPGKGLEWMGG BLN3 Heavy chain 181 FDPEDAETIYAQKFQGRVTMTEDTSTDRAYMELSSLRSEDTAVYYCVAAPVI amino acid sequence TGSPEAYSYYYGMDVWGQGTTVTVSS QSALTQPASLSGSPGQSITISCTGTSSDVGSYNLVSWYQQHPGKTPKVIIYEVT BLN3 Light chain 182 NRASGVSNRFSGSQSGNTASLTISGLQAEDEADYYCSSYTRTSTLDVVFGGGT amino acid sequence ELTVL QLQLQESGPGLVKPSQTLSLTCTVSGGSISSGSYYWSWIRQPAGKGLEWIGRI BLN4 Heavy chain 183 YTTGSTSYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARMAYQVY amino acid sequence YYDSSGYYDAFDIWGQGTMVTVSS NFMLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSKNQ BLN4 Light chain 184 RPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCSAWDDSLRGYVFGPGTKV amino acid sequence TVL QVQLQESGAEVKKLGLSEGLCKVSGYTLTELSMHWVRQAPGKGLEWMGGF BLN5 Heavy chain 185 DPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCVTAPVIT amino acid sequence GSPEAYSYYYGMDVWGQGTTVTVSS QSALTQPASVSGPPGQSITISCTGTSSDIGGYNLVSWYQQHPGKAPKLMIYEGT BLN5 Light chain 186 KRPSGVSYRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSPTLWVFGGGTK amino acid sequence VTVL QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGSYYWSWIRQPAGKGLEWIGRI BLN6 Heavy chain 187 YTTGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARMAYQVY amino acid sequence YYDSSGYYDAFDIWGQGTMVTVSS QSALTQPASASGSPGQSVTISCTGSSSDVGGYNFVSWYQQHPGKAPKLIIYEV BLN6 Light chain 188 SKRPSGVPNRFSGSKSGNTASLTVSGLQADDEALYYCSSYAGSNNYVFGPGT amino acid sequence KVTVL EVQLVQSGAEVKKPGASVKVSCKVSGYTLPELSMHWVRQAPGKGLEWMGG BLN7 Heavy chain 189 FDPEDGGTIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATSRVA amino acid sequence GTPNWFHPWGQGTLVTVSS QSVLTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDV BLN7 Light chain 190 SNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTLVFGTGTKV amino acid sequence TVL EVQLLESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLQWVALI BLN8 Heavy chain 191 SYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLGS amino acid sequence GWYPWGQGTLVTVSS NFMLTQPPSVSVSPGQTASITCSGDKLGDKYASWYQQKPGQSPVLVIYQDSK BLN8 Light chain 192 RPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTVVFGGGTELTV amino acid sequence L QVQLVQSGAGVKKPGASVKVSCKVSGYTLPELSMHWVRQAPGKGLEWMG BLN9 Heavy chain 193 GFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATSRV amino acid sequence AGTPNWFHPWGQGTLVTVSS QSALTQPVSVSGSPGQSITISCTGTSSDVGRYNYVSWYQQHPGKAPKLIIYDV BLN9 Light chain 194 KNRPSGVPDRFSGSKSGNTASLTISGLQAEDEADYYCSSYTRSSTLDVVFGGG amino acid sequence TELTVL QVQLVQSGAEVKKPGASVKVSCKVSGYTLPELSMHWVRQAPGKGLEWMGG BLN10 Heavy chain 195 FDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATGPAI amino acid sequence AAAATGWFDPWGQGTLVTVSS SYELIQEPSVSVSPGQTARITCQGDSLRSYYASWYQQKPGQAPVLVIYNRNKR BLN10 Light chain 196 PSGIPDRFSGSSSGNTASLTITGAQADDEADYYCNSRDNSGNHPFGGGTKVTV amino acid sequence L QVQLQQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGG BLN12 Heavy chain 197 FDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCVTAPVIT amino acid sequence GSPEAYSYYYGMDVWGQGTTVTVSS DIVMTQSPLSSPVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPGQPPRLLIY BLN12 Light chain 198 KISNRFSGVPDRFSGSGAGTDFTLKISRVEAEDVGVYYCMQATQFPITFGGGT amino acid sequence KVEIK QMQLVQSGGGVVQPGRSLRLSCAASGSTFSSYGMHWVRQAPGKGLEWVAV BLN14 Heavy chain 199 ISFDGSNKFYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDHDD amino acid sequence GYYFYYYMDVWGKGTTVTVSS EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASS BLN14 Light chain 200 RATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSRTFGGGTRLEIK amino acid sequence Table 8: CDR amino acid sequences of the anti-RBD SARS-Cov-2 antibodies SEQ Sequence Description ID NO.

GFIFDDYAMH BL1 Heavy chain 201 CDR H1 GISWNSGSIGYAVSVKG BL1 Heavy chain 202 CDR H2 APLGELLPGDWFDP BL1 Heavy chain 203 CDR H3 TGTSSDVGAFNYVS BL1 Light chain 204 CDR L1 DVTKRPS BL1 Light chain 205 CDR L2 ASYAGSNNFVFGT BL1 Light chain 206 CDR L3 GFIFDDYAMH BL2 Heavy chain 207 CDR H1 GISWNSGSIGYAVSVKG BL2 Heavy chain 208 CDR H2 APLGELLPGDWFDP BL2 Heavy chain 209 CDR H3 SGSRSNIGNNYVS BL2 Light chain 210 CDR L1 SNNQRPS BL2 Light chain 211 CDR L2 AAWDDSLNGWVFGG BL2 Light chain 212 CDR L3 GFTFEDYDMQ BL3 Heavy chain 213 CDR H1 GISWNGGIIGYGDSVKG BL3 Heavy chain 214 CDR H2 ALHSGDDSGQQAFDI BL3 Heavy chain 215 CDR H3 GGNNIGAKSVH BL3 Light chain 216 CDR L1 DDSDRPP BL3 Light chain 217 CDR L2 QVWDSSSDHVIFGG BL3 Light chain 218 CDR L3 GLTVSRNYMS BL5 Heavy chain 219 CDR H1 LIYSGGSTYYADSVKG BL5 Heavy chain 220 CDR H2 DLVVYGMDV BL5 Heavy chain 221 CDR H3 GGNNIGSKSVH BL5 Light chain 222 CDR L1 YDSDRPS BL5 Light chain 223 CDR L2 QVWDSSSDHVVFGG BL5 Light chain 224 CDR L3 GFTFEDYDMQ BL6 Heavy chain 225 CDR H1 GISWNGGIIGYGDSVKG BL6 Heavy chain 226 CDR H2 ALHSGDDSGQQAFDI BL6 Heavy chain 227 CDR H3 GENNIGRRSVH BL6 Light chain 228 CDR L1 NDSDRPS BL6 Light chain 229 CDR L2 QVWDSGSDHVVFGG BL6 Light chain 230 CDR L3 GFTFSTYSMN BL7 Heavy chain 231 CDR H1 YISSSGNTMYYADSVKG BL7 Heavy chain 232 CDR H2 DHGIGYETEGPDY BL7 Heavy chain 233 CDR H3 SGSSSNIGSNYVY BL7 Light chain 234 CDR L1 RNNQRPS BL7 Light chain 235 CDR L2 AAWDDSLSGVVFGG BL7 Light chain 236 CDR L3 GGSFSSYTIS BL8 Heavy chain 237 CDR H1 RIIPILGIANYAQKFQG BL8 Heavy chain 238 CDR H2 DRGYSSSGSNYYMDV BL8 Heavy chain 239 CDR H3 TGSSSNIGAGYDVH BL8 Light chain 240 CDR L1 GNSNRPS BL8 Light chain 241 CDR L2 QSYDSSLSGSGVFGG BL8 Light chain 242 CDR L3 GFTVSSNYMS BL9 Heavy chain 243 CDR H1 TIYSGGSTYYADSVKG BL9 Heavy chain 244 CDR H2 GDGSDNYYYGMDV BL9 Heavy chain 245 CDR H3 TGNSSNIGAGYDVH BL9 Light chain 246 CDR L1 GNTNRPS BL9 Light chain 247 CDR L2 AAWDDSLSGLFGG BL9 Light chain 248 CDR L3 GYTLTELSMH BL10 Heavy chain 249 CDR H1 GFDPEDAETIYAQKFQG BL10 Heavy chain 250 CDR H2 APVITGSPEAYSYYYGMDV BL10 Heavy chain 251 CDR H3 TGTNNDIGGYNLVS BL10 Light chain 252 CDR L1 EVDQRPS BL10 Light chain 253 CDR L2 SSYTSTNTHVFGG BL10 Light chain 254 CDR L3 GYTLTELSMH BL11 Heavy chain 255 CDR H1 GFDPEDAETIYAQKFQG BL11 Heavy chain 256 CDR H2 APVITGSPEAYSYYYGMDV BL11 Heavy chain 257 CDR H3 TGTSSDVGGYNYVS BL11 Light chain 258 CDR L1 EVSKRPS BL11 Light chain 259 CDR L2 SSYTISSTYVFGT BL11 Light chain 260 CDR L3 GYTLPELSMH BL12 Heavy chain 261 CDR H1 GFDPEDGETIYAQKFQG BL12 Heavy chain 262 CDR H2 GPAIAAAATGWFDP BL12 Heavy chain 263 CDR H3 AGTSSDVGSYNRVS BL12 Light chain 264 CDR L1 EVSNRPS BL12 Light chain 265 CDR L2 SSYSSSSTVVFGG BL12 Light chain 266 CDR L3 GLTVSRNYMS BLK2 Heavy chain 267 CDR H1 LIYSGGSTYYAGSVKG BLK2 Heavy chain 268 CDR H2 DLVVYGMDV BLK2 Heavy chain 269 CDR H3 QASQDINKYLN BLK2 Light chain 270 CDR L1 DASNLET BLK2 Light chain 271 CDR L2 QQYDNVPPSFGQ BLK2 Light chain 272 CDR L3 GFTVSRNYMS BLK3 Heavy chain 273 CDR H1 IIYSGGSTFYADSVKG BLK3 Heavy chain 274 CDR H2 DLDVVGGMDV BLK3 Heavy chain 275 CDR H3 RASQSVSGSYLA BLK3 Light chain 276 CDR L1 DASSRAT BLK3 Light chain 277 CDR L2 QQYGSSSWTFGQ BLK3 Light chain 278 CDR L3 GVTVSSNYMS BLK10 Heavy chain 279 CDR H1 VIYSGGSTYYADSVKG BLK10 Heavy chain 280 CDR H2 DLAGEWGFDI BLK10 Heavy chain 281 CDR H3 RASQSISSYVN BLK10 Light chain 282 CDR L1 AASSLQS BLK10 Light chain 283 CDR L2 QQTYITPYSFGQ BLK10 Light chain 284 CDR L3 GLTVSRNYMS BLK14 Heavy chain 285 CDR H1 LIYSGGSTYYADSVKG BLK14 Heavy chain 286 CDR H2 DLVVYGMDV BLK14 Heavy chain 287 CDR H3 RASHDIGGYVA BLK14 Light chain 288 CDR L1 DTSSRAT BLK14 Light chain 289 CDR L2 QQYGTSPLTFGG BLK14 Light chain 290 CDR L3 GLTVSRNYMS BLK15 Heavy chain 291 CDR H1 LIYSGGSTYYADSVKG BLK15 Heavy chain 292 CDR H2 DLVVYGMDV BLK15 Heavy chain 293 CDR H3 RASQSVSNYLA BLK15 Light chain 294 CDR L1 AASSRAT BLK15 Light chain 295 CDR L2 QQYGSSPLTFGG BLK15 Light chain 296 CDR L3 GLTVSRNYMS BLK21 Heavy chain 297 CDR H1 LIYSGGSTYYADSVKG BLK21 Heavy chain 298 CDR H2 DLVVYGMDV BLK21 Heavy chain 299 CDR H3 RASQSISSYLN BLK21 Light chain 300 CDR L1 AASSLQS BLK21 Light chain 301 CDR L2 QQSDSSPLTFGG BLK21 Light chain 302 CDR L3 AASGLTVSRNYMS BLK23 Heavy chain 303 CDR H1 LIYSGGSTYYADSVKG BLK23 Heavy chain 304 CDR H2 DLVVYGMDV BLK23 Heavy chain 305 CDR H3 RASQGISNYLA BLK23 Light chain 306 CDR L1 SASTLQS BLK23 Light chain 307 CDR L2 QQLNSYPLTFGG BLK23 Light chain 308 CDR L3 Table 9: CDR amino acid sequences of the anti-NTD SARS-Cov-2 antibodies SEQ Sequence Description ID NO.

GYTLTELSMH BLN1 Heavy chain 309 CDR H1 GFDPEDAETIYAQKFQG BLN1 Heavy chain 310 CDR H2 APAITGSPEAYSYYYSVDV BLN1 Heavy chain 311 CDR H3 RSSQSLVHSDGNTYLS BLN1 Light chain 312 CDR L1 KTSNRFF BLN1 Light chain 313 CDR L2 LQATQFPYTFGQ BLN1 Light chain 314 CDR L3 GYTLTELSMH BLN2 Heavy chain 315 CDR H1 GFDPEDGETIYAQKFQG BLN2 Heavy chain 316 CDR H2 SPAVRGSPSNFYYYHGMDV BLN2 Heavy chain 317 CDR H3 TGSSSDIGGYNYVS BLN2 Light chain 318 CDR L1 EGSKRPS BLN2 Light chain 319 CDR L2 SSYTSSSTLVFGG BLN2 Light chain 320 CDR L3 GYTLTELSMH BLN3 Heavy chain 321 CDR H1 GFDPEDAETIYAQKFQG BLN3 Heavy chain 322 CDR H2 APVITGSPEAYSYYYGMDV BLN3 Heavy chain 323 CDR H3 TGTSSDVGSYNLVS BLN3 Light chain 324 CDR L1 EVTNRAS BLN3 Light chain 325 CDR L2 SSYTRTSTLDVVFGG BLN3 Light chain 326 CDR L3 GGSISSGSYYWS BLN4 Heavy chain 327 CDR H1 RIYTTGSTSYNPSLKS BLN4 Heavy chain 328 CDR H2 MAYQVYYYDSSGYYDAFDI BLN4 Heavy chain 329 CDR H3 SGSSSNIGSNTVN BLN4 Light chain 330 CDR L1 SKNQRPS BLN4 Light chain 331 CDR L2 SAWDDSLRGYVFGP BLN4 Light chain 332 CDR L3 GYTLTELSMH BLN5 Heavy chain 333 CDR H1 GFDPEDAETIYAQKFQG BLN5 Heavy chain 334 CDR H2 APVITGSPEAYSYYYGMDV BLN5 Heavy chain 335 CDR H3 TGTSSDIGGYNLVS BLN5 Light chain 336 CDR L1 EGTKRPS BLN5 Light chain 337 CDR L2 SSYAGSPTLWVFGG BLN5 Light chain 338 CDR L3 GGSISSGSYYWS BLN6 Heavy chain 339 CDR H1 RIYTTGSTNYNPSLKS BLN6 Heavy chain 340 CDR H2 MAYQVYYYDSSGYYDAFDI BLN6 Heavy chain 341 CDR H3 TGSSSDVGGYNFVS BLN6 Light chain 342 CDR L1 EVSKRPS BLN6 Light chain 343 CDR L2 SSYAGSNNYVFGP BLN6 Light chain 344 CDR L3 GYTLPELSMH BLN7 Heavy chain 345 CDR H1 GFDPEDGGTIYAQKFQG BLN7 Heavy chain 346 CDR H2 SRVAGTPNWFHP BLN7 Heavy chain 347 CDR H3 TGTSSDVGGYNYVS BLN7 Light chain 348 CDR L1 DVSNRPS BLN7 Light chain 349 CDR L2 SSYTSSSTLVFGT BLN7 Light chain 350 CDR L3 GFTFSSYAMH BLN8 Heavy chain 351 CDR H1 LISYDGSNKYYADSVKG BLN8 Heavy chain 352 CDR H2 DLGSGWYP BLN8 Heavy chain 353 CDR H3 SGDKLGDKYAS BLN8 Light chain 354 CDR L1 QDSKRPS BLN8 Light chain 355 CDR L2 QAWDSSTVVFGG BLN8 Light chain 356 CDR L3 GYTLPELSMH BLN9 Heavy chain 357 CDR H1 GFDPEDGETIYAQKFQG BLN9 Heavy chain 358 CDR H2 SRVAGTPNWFHP BLN9 Heavy chain 359 CDR H3 TGTSSDVGRYNYVS BLN9 Light chain 360 CDR L1 DVKNRPS BLN9 Light chain 361 CDR L2 SSYTRSSTLDVVFGG BLN9 Light chain 362 CDR L3 GYTLPELSMH BLN10 Heavy chain 363 CDR H1 GFDPEDGETIYAQKFQG BLN10 Heavy chain 364 CDR H2 GPAIAAAATGWFDP BLN10 Heavy chain 365 CDR H3 QGDSLRSYYAS BLN10 Light chain 366 CDR L1 NRNKRPS BLN10 Light chain 367 CDR L2 NSRDNSGNHPFGG BLN10 Light chain 368 CDR L3 GYTLTELSMH BLN12 Heavy chain 369 CDR H1 GFDPEDAETIYAQKFQG BLN12 Heavy chain 370 CDR H2 APVITGSPEAYSYYYGMDV BLN12 Heavy chain 371 CDR H3 RSSQSLVHSDGNTYLS BLN12 Light chain 372 CDR L1 KISNRFS BLN12 Light chain 373 CDR L2 MQATQFPITFGG BLN12 Light chain 374 CDR L3 GSTFSSYGMH BLN14 Heavy chain 375 CDR H1 VISFDGSNKFYADSVKG BLN14 Heavy chain 376 CDR H2 DHDDGYYFYYYMDV BLN14 Heavy chain 377 CDR H3 RASQSVSSSYLA BLN14 Light chain 378 CDR L1 GASSRAT BLN14 Light chain 379 CDR L2 QQYGSSRTFGG BLN14 Light chain 380 CDR L3 The CDR sequences are highlighted within the heavy and the light chain amino acid sequences.

The present invention also encompasses variants of the heavy and light chain variable regions. The variants may include mutations in the complementarity determining regions of the heavy and light chains which do not alter the activity of the antibodies herein described, or in the framework region.

By the term “variant” it is meant sequences of amino acids or nucleotides different from the sequences specifically identified herein, in which one or more amino acid residues or nucleotides are deleted, substituted, or added.

It should be appreciated that by the term "added ", as used herein it is meant any addition of amino acid residues to the sequences described herein.

Variants encompass various amino acid substitutions. An amino acid “substitution” is the result of replacing one amino acid with another amino acid which has similar or different structural and/or chemical properties. Amino acid substitutions may be made based on similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved.

Typically, variants encompass conservative amino acid substitutions.

Conservative substitution tables providing functionally similar amino acids are well known in the art. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid.

Each of the following eight groups contains other exemplary amino acids that are conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); ) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M).

Conservative nucleic acid substitutions are nucleic acid substitutions resulting in conservative amino acid substitutions as defined above.

Variants in accordance with the invention also encompass non-polar to polar amino acid substitutions and vice-versa.

As used herein, the term “amino acid” or “amino acid residue” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids.

Variant sequences refer to amino acid or nucleic acids sequences that may be characterized by the percentage of the identity of their amino acid or nucleotide sequences with the amino acid or nucleotide sequences described herein (for example, the amino acid or nucleotide sequences of the heavy and light chains of the antibodies herein described).

In some embodiments, variant sequences as herein defined refer to nucleic acid sequences that encode the heavy and light chain variable regions, each having a sequence of nucleotides with at least 70% or 75% of sequence identity, around 80% or 85% of sequence identity, around 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of sequence identity when compared to the sequences of the heavy and light chain variable regions described herein.

By the term “activity of the antibodies” it is meant the ability of the antibodies to bind SARS Cov2 spike protein, and preferably to inhibit the ability of SARS-CoV-2 virus to infect mammalian cells. The activity of the antibodies can be measured in vivo or in vitro using methods well known in the art, e.g. as described in the Examples below.

The binding of the antibody of the invention to its target protein may be measured for example using ELISA, biolayer interferometry (BLI), Western blot or IFA assays.

The biological activity of the antibodies can be measured for example in a functional assay testing the infectivity of SARS-CoV-2 virus in cultured mammalian cells for example as detailed in the Examples below.

In another one of its aspects the present invention provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding an antibody or antigen-binding fragment thereof according to the invention.

The term “nucleic acid” or “nucleic acid molecule” as herein defined refers to a polymer of nucleotides, which may be either single- or double-stranded, which is a polynucleotide such as deoxyribonucleic acid (DNA), and, where appropriate, ribonucleic acid (RNA). The terms should also be understood to include, as equivalents, analogs of either RNA or DNA made from nucleotide analogs, and, as applicable to the embodiment being described, single-stranded (such as sense or antisense) and double-stranded polynucleotides. The term DNA used herein also encompasses cDNA, i.e. complementary or copy DNA produced from an RNA template by the action of reverse transcriptase (RNA-dependent DNA polymerase).

The invention further provides an expression vector comprising the isolated nucleic acid molecule as herein defined.

“Expression vector” sometimes referred to as “expression vehicle” or “expression construct”, as used herein, encompasses vectors such as plasmids, viruses, bacteriophage, integratable DNA fragments, and other vehicles, which enable the integration of DNA fragments into the genome of the host. Expression vectors are typically self-replicating DNA or RNA constructs containing the desired gene or its fragments, and operably linked genetic control elements that are recognized in a suitable host cell and effect expression of the desired genes. These control elements are capable of effecting expression within a suitable host. The expression vector in accordance with the invention may be competent with expression in bacterial, yeast, or mammalian host cells, to name but few.

In yet another one of its aspects the present invention provides a host cell transfected with the isolated nucleic acid molecule according to the invention or with the expression vector according to the invention.

The term "host cells” as used herein refers to cells which are susceptible to the introduction of the isolated nucleic acid molecule according to the invention or with the expression vector according to the invention. Preferably, said cells are mammalian cells, for example CHO cells or NS0 cells. Transfection of the isolated nucleic acid molecule or the expression vector according to the invention to the host cell may be performed by any method known in the art.

In yet another one of its aspects the present invention provides an immunoconjugate comprising the antibody or antigen-binding fragment thereof according to the invention and an additional therapeutic agent as defined herein below.

The term “immunoconjugate” as herein defined refers to an antibody or antigen- binding fragment thereof according to the invention that is conjugated (linked or joined) to an additional agent. Immunoconjugates may be prepared by any method known to a person skilled in the art, for example, by cross-linking the additional agent to the antibody according to the invention or by recombinant DNA methods.

The anti SARS Cov2 spike protein antibody of the invention may be administered in combination with at least one additional therapeutic agent.

The term “additional therapeutic agent” used herein refers to any agent that may be used for treating COVID19. In accordance with certain embodiments said at least one additional therapeutic agent is selected from a group consisting of anti SARS Cov2 antibodies, antiviral agents, or anti-inflammatory agents.

In certain embodiments the additional therapeutic agent is an additional antibody.

The term “additional antibody” as herein defined refers to antibodies of the invention (namely to the combined use of at least two antibodies of the invention, for example but not limited to the combination of an anti Spike RBD and anti Spike NTD antibodies) as well as to an antibody, which is not the antibody according to the invention, which may be used in combination with the antibody of the invention for treating COVID19.

The present invention further provides a pharmaceutical composition comprising as an active ingredient at least one isolated anti SARS Cov2 spike protein antibody of the invention, or antigen-binding fragment thereof or the immunoconjugate as herein defined and a pharmaceutically acceptable carrier, excipient or diluent.

In a specific embodiment, said pharmaceutical composition is for use in the treatment of a SARS Cov2 infection (i.e. COVID19) or for use in inhibiting SARS COV2 uptake by the subject's cells.

The “pharmaceutical composition” of the invention generally comprises the antibody or any antigen-binding fragment thereof as herein defined and a buffering agent, an agent which adjusts the osmolarity of the composition and optionally, one or more pharmaceutically acceptable carriers, excipients and/or diluents as known in the art.

As used herein the term “pharmaceutically acceptable carrier, excipient or diluent” includes any solvents, dispersion media, coatings, antibacterial and antifungal agents and the like, as known in the art. The carrier can be solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils.

Each carrier should be both pharmaceutically and physiologically acceptable in the sense of being compatible with the other ingredients and not injurious to the subject. Except as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic composition is contemplated.

In other embodiments the pharmaceutical composition according to the invention further comprises an additional therapeutic agent. Non-limiting examples of additional therapeutic agents include anti SARS Cov2 spike protein antibodies and antiviral agents (e.g. remdesivir). Thus, in specific embodiments the pharmaceutical composition according to the invention further comprises an additional therapeutic agent which is an antiviral agent.

In specific embodiments the present invention relates to a pharmaceutical composition comprising at least one isolated anti SARS Cov2 spike protein antibody, or any antigen-binding fragment thereof, wherein the antibody comprises: (a) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 17 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 18, or a variant thereof; or (b) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 19 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 20, or a variant thereof; or (c) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 21 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 22, or a variant thereof; or (d) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 23 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 24, or a variant thereof [Add sequences of Ab1]; or (e) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 25 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 26, or a variant thereof; or (f) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 27 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 28, or a variant thereof; or (g) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 29 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 30, or a variant thereof; or (h) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 31 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 32, or a variant thereof.

In other specific embodiments the pharmaceutical composition comprises any of the antibodies having SEQ ID Nos. as described in Tables 1-8.

The present invention also provides methods of prophylaxis, treatment or amelioration of SARS Cov2 infection or COVID19 comprising administering to a subject in need thereof a therapeutically effective amount of the isolated monoclonal antibody or antigen-binding fragment thereof of the invention, or an immune-conjugate comprising the antibody or antigen-binding fragment thereof of the invention or a pharmaceutical composition comprising the isolated monoclonal antibody or antigen-binding fragment thereof or the immune-conjugate of the invention.

The term “SARS Cov-2 infection” is used herein at its broadest sense and refers to any infection caused by Severe acute respiratory syndrome coronavirus 2 (SARS Cov- 2). The term “COVID 19” as known in the art refers to an infectious disease caused by the virus SARS Cov-2. Symptoms include for example fever, dry cough, dyspnea, fatigue, and lymphopenia in infected patients. In more severe cases, infections causing viral pneumonia characterized primarily by fever, cough, dyspnea, and bilateral infiltrates may lead to severe acute respiratory syndrome (SARS) and even death.

The invention also provides a method of inhibiting SARS Cov-2 infection of mammalian cultured cells in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the isolated monoclonal antibody or antigen- binding fragment thereof of the invention, or an immune-conjugate comprising the antibody or antigen-binding fragment thereof of the invention or a pharmaceutical composition comprising the isolated monoclonal antibody or antigen-binding fragment thereof or the immune-conjugate of the invention.

The terms "subject" or "patient" are used interchangeably and refer to a subject that may benefit from the present invention such as a mammal (e.g. canine, feline, ovine, porcine, equine, bovine, or human). In one specific embodiment the patient is human.

Diagnosis of SARS Cov-2 infection may be performed by a skilled physician by methods known in the art. The term “subject in need thereof” in the context of the present invention inter alia refers to mammals and in particular to human subjects suffering from SARS Cov-2 infection or COVID19 as defined herein. The term “subject in need thereof” further encompasses mammals and in particular human subjects at risk of being infected by SARS Cov-2 (including but not limited to health care practitioners, subjects having a compromised immune system, elderly people and subjects suffering from other diseases, for example chronic diseases).

By the term “prophylaxis” as herein defined it is meant to provide a "preventive treatment" or "prophylactic treatment", namely acting in a protective manner, to defend against or prevent the appearance of a symptom of SARS Cov-2 infection, or COVID19 onset or progression.

It is to be understood that the terms "treat”, “treating”, “treatment" or forms thereof, as used herein, mean reducing, preventing, curing, reversing, ameliorating, attenuating, alleviating, minimizing, suppressing or halting the deleterious effects of a disease or a condition or delaying the onset of one or more clinical indications of SARS Cov-2 infection, or COVID19, as defined herein. In some embodiments the methods according to the invention are wherein said methods further comprise administering to a subject in need thereof an additional therapeutic agent as herein defined.

Administration according to the present invention may be performed by any of the following routes: oral administration, intravenous, intramuscular, intraperitoneal, intrathecal, or subcutaneous injection; intra-rectal administration; intranasal administration, ocular administration, or topical administration.

In specific embodiments administration according to the present invention may be performed intravenously. In other specific embodiments administration may be performed intraperitoneally. In other specific embodiments administration may be performed by inhalation.

The antibodies or antibody fragments as herein defined, any pharmaceutical compositions comprising the same or any conjugates comprising them may be administered to a subject prior to or post disease onset, in a single dose or in multiple doses.

Thus in some embodiments the method of prophylaxis, treatment or amelioration of SARS Cov-2 infection according to the invention is where said isolated anti SARS Cov-2 spike protein antibody or any antigen-binding fragment thereof according to the invention, or pharmaceutical composition according to the invention is administered to said subject prior to or after disease onset.

A “therapeutically effective amount” of the isolated monoclonal antibody or any antigen-binding fragment thereof according to the invention, or the pharmaceutical composition according to the invention for purposes herein defined is determined by such considerations as are known in the art in order to cure, arrest or at least alleviate or ameliorate the medical condition. For any preparation used in the methods of the invention, the dosage or the therapeutically effective amount can be estimated initially from in vitro cell culture assays or based on suitable animal models.

In some embodiments the therapeutically effective amount in accordance with the invention is in the range of 10 µg/kg to about 50 mg/kg.

In other embodiments the therapeutically effective amount in accordance with the invention is in the range of 0.1 mg/kg to 40 mg/kg, 1 mg/kg to 10 mg/kg, or 5 mg/kg to mg/kg.

In other embodiments the isolated anti SARS Cov-2 spike protein antibody or any antigen-binding fragment thereof according to the invention or pharmaceutical composition according to the invention is administered to the subject as a single dose or as multiple doses.

Specific exemplary doses include, but are not limited to 0.75 mg/kg, or 2.5 mg/kg, or 5 mg/kg, or 10 mg/kg each given as a single daily dose. In one embodiment, the doses are given intravenously.

The present invention further provides the isolated anti SARS Cov-2 spike protein antibody or any antigen-binding fragment thereof according to the invention or the pharmaceutical composition according to the invention for use in a method of prophylaxis, treatment or amelioration of SARS Cov-2 infection or COVID19 as defined herein.

Still further the present invention provides use of the isolated monoclonal antibody or antigen-binding fragment thereof, the immune-conjugate comprising the antibody or antigen-binding fragment thereof or the pharmaceutical composition comprising the isolated monoclonal antibody or antigen-binding fragment thereof or the immune-conjugate of the invention in the preparation of a medicament for the prophylaxis, treatment or amelioration of SARS Cov-2 infection or COVID19 or in the preparation of a medicament for inhibiting SARS Cov-2 uptake by cells in a subject.

In specific embodiments the invention provides an isolated scFv-Fc anti SARS Cov-2 spike protein antibody fragment, wherein the antibody fragment comprises: (a) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 17 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 18, or a variant thereof; or (b) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 19 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 20, or a variant thereof; or (c) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 21 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 22, or a variant thereof; or (d) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 23 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 24, or a variant thereof; or (e) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 25 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 26, or a variant thereof; or (f) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 27 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 28, or a variant thereof; or (g) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 29 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 30, or a variant thereof; or (h) a heavy chain variable region of the amino acid sequence denoted by SEQ ID NO. 31 or a variant thereof and a light chain variable region of the amino acid sequence denoted by SEQ ID NO. 32, or a variant thereof for use in a method of prophylaxis, treatment, or amelioration of SARS Cov-2 infection or COVID19 as defined herein.

In other embodiments the invention provides an isolated scFv-Fc anti SARS Cov- 2 spike protein antibody fragment, wherein the antibody fragment comprises a heavy chain variable region and a light chain variable region as disclosed in any of Tables 1-8, or a variant thereof, for use in a method of prophylaxis, treatment, or amelioration of SARS Cov-2 infection or COVID19 as defined herein.

It is appreciated that the term “purified” or "isolated" refers to molecules, such as amino acid or nucleic acid sequences, peptides, polypeptides, or antibodies that are removed from their natural environment, isolated, or separated. An “isolated antibody” is therefore a purified antibody. As used herein, the term “purified” or “to purify” also refers to the removal of contaminants from a sample.

In another aspect, the present invention provides a method of detecting SARS Cov-2 in a sample, said method comprising: a. contacting said sample with the isolated monoclonal antibody or antigen- binding fragment thereof of the invention; and b. detecting said isolated monoclonal antibody or any antigen-binding fragment thereof; wherein the presence of said isolated monoclonal antibody or any antigen-binding fragment thereof indicates the presence of SARS Cov-2 spike protein in said sample.

Detecting the isolated antibodies in accordance with the present invention may be performed by any method known in the art, for example by immobilizing the antibody of the invention as the capture reagent in an ELISA assay. In various embodiments the isolated antibodies in accordance with the present invention may be labeled according to any methods known in the art. In other embodiments detection may be based on identifying said antibodies using secondary antibodies. Other detection assays include but are not limited to Biolayer interferometry-based assay (Mechaly et al. 2016).

In one embodiment the sample is obtained from various environmental surfaces such as furniture, desks and the like.

In another embodiment, the sample is a biological sample obtained from a subject.

The term “biological sample” is used herein in its broadest sense and refers to any sample taken from a subject as herein defined in which SARS Cov-2 may be detected. Biological samples may be obtained from mammals (including humans) and encompass fluids, solids and tissues. In some embodiments the biological sample is blood, plasma, serum, lymph fluid, urine, a tissue sample, a biopsy sample, or a cell lysate.

The present disclosure further provides a kit for detecting SARS Cov-2 infection comprising: (a) at least one isolated monoclonal antibody or antigen-binding fragment thereof according to the present disclosure; (b) means for detection of said isolated monoclonal antibody; and optionally (c) instructions for use of said kit.

The term "about" as used herein indicates values that may deviate up to 1%, more specifically 5%, more specifically 10%, more specifically 15%, and in some cases up to % higher or lower than the value referred to, the deviation range including integer values, and, if applicable, non-integer values as well, constituting a continuous range.

Disclosed and described, it is to be understood that this invention is not limited to the examples, methods steps, and compositions disclosed herein as such methods steps and compositions may vary somewhat. It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only and not intended to be limiting since the scope of the present invention will be limited only by the appended claims and equivalents thereof.

It must be noted that, as used in this specification and the appended claims, the singular forms “a”, “an” and “the” include plural referents unless the content clearly dictates otherwise.

Throughout this specification and the Examples and claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

EXAMPLES Materials and Methods Single chain variable fragment (scFv) Library Construction RNA was extracted from blood samples obtained from human patients which were positively tested for COVID-19 and was used as a template for first-strand cDNA synthesis, essentially as described in Mechaly A. et al. 2018. A set of degenerate primers was designed to cover all known human VH, Vλ and Vk immunoglobulin families. The construction of the scFv library was performed by assembly PCR of the VH and Vκ or VH and Vλ fragments (Noy-Porat T. et al. 2016). The scFv gene fragments were then ligated into linearized pCC plasmid (Rosenfeld R. et al. 2009) and transformed into E. 16 coli TG1 electro-competent cells (Lucigen, Middleton, WI, USA). The transformed bacteria, containing the final scFv library, were plated on YPD agar (BD, Franklin Lakes, NJ, USA) supplemented with 100 µg/mL ampicillin and 100 mM glucose and, after an overnight culture at 30 °C, were harvested, aliquoted and stored at −80 °C.

Library Screening For library packaging, 200 mL Yeast Extract–Peptone–Dextrose (YPD) medium, containing 100 µg/mL ampicillin and 100 mM glucose, were inoculated with 0.5 mL of the harvested bacteria containing the scFv library. Bacteria were grown in a shaker incubator (New Brunswick Scientific, Enfield, CT, USA) at 37 °C, 220 rpm to an O.D. 600 of 0.7. Bacteria (10 mL) were than infected with 700 µL of M13KO7 helper phage (New England Biolabs, Ipswich, MA, USA) by incubating at 37 °C for 60 minutes (min) without shaking, followed by 60 min at 120 rpm. Infected cells were then harvested (5 min, 4000 rpm) and re-suspended in 50 mL YPD with 100 µg/mL ampicillin and 50 µg/mL kanamycin. After an overnight culture at 30 °C at 200 rpm, cells were pelleted by centrifugation for 10 min, 4000 rpm at 4 °C, and the supernatant containing the phages was filtered through a 0.45-µm filter and then precipitated with 1/5 volume of 20% PEG6000 (polyethylene glycol)/2.5 M NaCl solution for 2 hours on ice. The phages were pelleted by centrifugation of 1 hour at 9000× g, 4 °C, and re-suspended in 5 mL PBS.

For library panning, antigen was presented by streptavidin magnetic beads (Dynabeads M-280, Invitrogen #11206D) or polystyrene plates (Nunc, Denmark) as detailed below. Human Fc fragment conjugated to the spike-related receptor binding domain (huFc-RBD) was biotinylated using a commercial kit (EZ-Link sulfo-NHS- biotin, pierce) and incubated with Streptavidin (SA) beads for 30 minutes (min). The phage display library was then added to the beads prepared as detailed above and the mixture was incubated for an additional period of 90 min. The beads were then washed with 3% bovine serum albumin (BSA) in phosphate buffered saline (PBS), followed by washing with phosphate buffered saline Tween-20 (PBST) and PBS.

Furthermore, non-biotinylated RBD (5 µg/ml) was used to coat a polystyrene 12 plate. Approximately 1 × 10 phage clones were blocked for 1 hour and then incubated for an additional hour with the RBD coated plate. The plate was then washed twice with blocking solution, four times with PBST (PBS, 0.05% Tween 20) and twice with PBS.

The bound phages, from both the above beads and plates, were eluted by incubation with 100 mM Triethylamine pH 3 (Sigma-Aldrich, St. Louis, MO, USA) for 30 min, followed by neutralization with 200μl Tris–HCl pH 7.5 (1M). The resulting phages were used to infect TG1 cells and grown over night for phage enrichment. The culture was then collected and used for phage rescue, to prepare the input for the next round of panning.

In total, three rounds of selection were used for isolating the antibodies. Single colonies were randomly picked from the second and third panning output, and phages were rescued and tested for their binding to RBD, spike-related S1 protein and inactivated COVID-19.

ELISA Maxisorp 96-well microtiter plates (Nunc, Sigma-Aldrich, St. Louis, MO, USA) were coated overnight (50 µL/well) with purified RBD or S1 proteins, then washed and blocked with PBST buffer (0.05% Tween 20, 2% BSA in PBS) for one hour. Individual phage clones or antibodies were added to the plates for a one-hour incubation; the plates were then washed with PBST and incubated with the detecting antibody: horseradish peroxidase (HRP)-conjugated anti-M13 antibody (GE healthcare, Little Chalfont, UK) for phage clones or anti-human IgG conjugated to alkaline phosphatase (Jackson immunoresearch, West Grove, PA, USA) for full antibodies. Detection of HRP conjugates was achieved with 3,3′,5,5′-tetramethybenzidine (TMB/E, Millipore, Billerica, MA, USA) while detection of alkaline phosphatase conjugates was achieved with SIGMAFAST p-nitrophenyl phosphate tablets (Sigma-Aldrich, St. Louis, MO, USA).

Nucleic Acid Analysis Phagemid DNA was isolated using the QIAprep spin Miniprep kit (Qiagen, GmbH, Hilden, Germany), and scFvs were sequenced by the SeqStudio Genetic Analyzer (Applied Biosystems, Foster City, CA, USA) using primers TAB-RI and CBD-AS (Noy- Porat T. et al. 2016).

Production of Full-Length Antibodies and SARS CoV-2 proteins Phagemid DNA of the antibody clones were isolated using QIAprep spin Miniprep kit (Qiagen, GmbH, Hilden, Germany), and VH and VL sequences were cloned into a mammalian scFv-Fc expression vector (Mechaly A. et al 2018). GenPept: QHD43416 ORF (open reading frame), coding to SARS CoV-2 spike glycoprotein was used to design pcDNA3.1+ based expression plasmids, mediating recombinant expression of the spike related proteins (S1, receptor binding domain (RBD), N-terminal domain (NTD) and S2). In addition, huFc-RBD fusion protein was also expressed, comprising a homodimer of two RBD moieties fused to a dimer of human Fc.

CHO-S cells (Thermo Scientific, Waltham, MA, USA) were transiently transfected with the vectors and after several days the supernatants were collected. The antibodies were purified on a HiTrap Protein-A column and the spike proteins were purified on HisTrap column (GE healthcare, Little Chalfont, UK).

SARS-CoV-2 in vitro plaque reduction neutralization assay 6 Vero E6 cells were seeded overnight at a density of 0.5 × 10 cells per well in 12- well plates in Dulbecco's Modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), Minimum Essential Medium (MEM) non-essential amino acids, 2 mM L-Glutamine, 100 Units/ml Penicillin, 0.1 mg/ml streptomycin, 12.5 Units/ml Nystatin (Biological Industries, Israel). Antibody samples were 2-fold diluted in 400 µl of MEM supplemented with 2% fetal bovine serum (FBS), MEM non-essential amino acids, 2 mM L-Glutamine, 100 Units/ml Penicillin, 0.1 mg/ml streptomycin, 12.5 Units/ml Nystatin (Biological Industries, Israel), and mixed with 400 µl of SARS-Cov-2 virus (150 pfu/ml) and incubated at 37 °C, 5% CO for 1 hour. Vero cell monolayers were 2 then washed once with DMEM medium without FBS and each Ab-virus mixture was added in triplicates to the cells for 1 hour. Non-neutralized virus served as control.

Medium at a 2 ml overlay (MEM containing 2% FBS and 0.4% tragacanth) was then added to each well and plates were further incubated at 37°C, 5% CO for 2 days. The 2 media were then aspirated and the cells were fixed and stained with 1 ml of crystal violet (Biological Industries, Israel). The number of plaques in each well was determined.

Example 1 Isolation of antibodies from COVID-19 patients Whole blood samples were obtained from human patients positively tested for COVID-19, total RNA was extracted, reverse-transcribed into cDNA and further used for construction of a phage-display library, as detailed above. Individual phage clones were selected as described above.

After panning and screening of the phage display library, eight different antibodies, termed MD17, MD29, MD45, MD47, MD62, MD63, MD65 and MD67 were isolated and sequenced, as described above. The nucleic acid sequences of the heavy and the light chains of the antibodies are shown in Table 1 above. The amino acid sequences of the heavy and the light chains of the antibodies are shown in Table 2 above and the amino acid sequences of the heavy chain CDRs and light chains CDRs of the antibodies are shown in Table 3 above.

Example 2 Characterization of the anti-SARS Cov-2 antibodies specificity The specific binding of seven antibodies was tested using direct ELISA against various SARS-CoV-2 related proteins. As can be seen in Figure 1, all clones strongly interact with the receptor binding domain (RBD), the S1 subunit (S1) and the spike protein without any significant binding to other parts of the spike protein, namely the N- terminal domain (NTD) or the S2 subunit (S2). These results imply that the selected set of antibodies are indeed directed to the RBD of the SARS-CoV-2.

Example 3 Binding assay of the anti-SARS Cov-2 antibodies to purified spike S1 protein To further characterize the binding of various antibodies, their affinity was evaluated using ELISA against the purified S1 protein (also referred to herein as the "S1 subunit"). Binding was normalized and expressed as percent of maximal binding, in order to correctly compare the activity of the antibodies. The apparent affinity of each antibody (K ) was then calculated as the antibody concentration at the half maximal binding point.

D These results (binding curves are shown in Figure 2) indicate that antibodies MD17 and MD29 possess the highest affinity toward the S1 protein (K of 2 nM) followed by D antibodies MD47, MD65 and MD67 (K of 5-12 nM) and antibodies MD45 and MD63 D (K of 38 nM and 47 nM, respectively).

D Example 4 Antibody mediated in vitro neutralization of SARS Cov-2 The SARS CoV-2 neutralization potency of each antibody was then evaluated using the plaque reduction neutralization assay as described above. In this assay, a fixed amount of virus is incubated with several concentrations of each of the tested antibodies and the mixture is added to Vero cells. The infectivity of SARS CoV-2 is determined by its ability to form measurable plaques in the culture cell monolayer and a sample that contains only virus is used as the 100% infectivity control. The number of plaques that were formed in the presence of each antibody was also evaluated, whereby virus neutralization is manifested in a reduction of the plaques that are formed. As shown in Figure 3, it was found that at a concentration of 100 g/ml, antibodies MD17, MD29 and MD47 neutralized >90% of the SARS-CoV-2 activity, thus demonstrating that they are an attractive candidates for a therapeutic preparation.

Example 5 Isolation of additional antibodies from COVID-19 (SARS CoV-2) patients In addition to the antibodies isolated as described above, further antibodies were obtained as detailed herein. Whole blood samples were obtained from seven human patients positively tested for COVID-19, and another phage display library was constructed as detailed above. Panning of the phage display library was conducted against either the receptor binding domain (RBD) or the N-terminal domain (NTD) proteins, and after screening, 18 antibodies (cloned as scFv-Fc) were isolated from the screen performed against RBD and 13 antibodies were isolated from the screen performed against NTD.

The specific binding of these antibodies was confirmed using direct ELISA against RBD versus NTD. SARS CoV-2 neutralization potency of each one of the antibodies was also evaluated using the plaque reduction neutralization assay as described above. As can be seen in Figure 4, the antibodies exhibited various degrees of In vitro neutralization activity. Particularly, some of the antibodies showed exceptional neutralization potency (for example BLK10, BLK14, BLK15, BLN1, or BLN14).

Claims

CLAIMS: 1. An isolated monoclonal antibody or antigen-binding fragment thereof which binds to Severe acute respiratory syndrome coronavirus 2 (SARS Cov-2) spike protein, wherein said antibody comprises: a. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 33, CDRH2 denoted by SEQ ID NO. 34, CDRH3 denoted by SEQ ID NO. 35, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 36, a CDRL2 denoted by SEQ ID NO. 37, and a CDRL3 denoted by SEQ ID NO. 38; or b. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 39, CDRH2 denoted by SEQ ID NO. 40, CDRH3 denoted by SEQ ID NO. 41, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 42, a CDRL2 denoted by SEQ ID NO. 43, and a CDRL3 denoted by SEQ ID NO. 44; or c. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 45, CDRH2 denoted by SEQ ID NO. 46, CDRH3 denoted by SEQ ID NO. 47, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 48, a CDRL2 denoted by SEQ ID NO. 49, and a CDRL3 denoted by SEQ ID NO. 50; or d. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 51, CDRH2 denoted by SEQ ID NO. 52, CDRH3 denoted by SEQ ID NO. 53, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 54, a CDRL2 denoted by SEQ ID NO. 55, and a CDRL3 denoted by SEQ ID NO. 56; or e. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 57, CDRH2 denoted by SEQ ID NO. 58, CDRH3 denoted by SEQ ID NO. 59, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 60, a CDRL2 94 denoted by SEQ ID NO. 61, and a CDRL3 denoted by SEQ ID NO. 62; or f. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 63, CDRH2 denoted by SEQ ID NO. 64, CDRH3 denoted by SEQ ID NO. 65, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 66, a CDRL2 denoted by SEQ ID NO. 67, and a CDRL3 denoted by SEQ ID NO. 68; or g. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 69, CDRH2 denoted by SEQ ID NO. 70, CDRH3 denoted by SEQ ID NO. 71, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 72, a CDRL2 denoted by SEQ ID NO. 73, and a CDRL3 denoted by SEQ ID NO. 74; or h. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 75, CDRH2 denoted by SEQ ID NO. 76, CDRH3 denoted by SEQ ID NO. 77, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 78, a CDRL2 denoted by SEQ ID NO. 79, and a CDRL3 denoted by SEQ ID NO. 80 i. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 201, CDRH2 denoted by SEQ ID NO. 202, CDRH3 denoted by SEQ ID NO. 203, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 204, a CDRL2 denoted by SEQ ID NO. 205, and a CDRL3 denoted by SEQ ID NO. 206; or j. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 207, CDRH2 denoted by SEQ ID NO. 208, CDRH3 denoted by SEQ ID NO. 209, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 210, a CDRL2 denoted by SEQ ID NO. 211, and a CDRL3 denoted by SEQ ID NO. 212; or k. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 213, CDRH2 denoted by SEQ ID NO. 214, CDRH3 denoted by SEQ ID NO. 215, and the light chain complementarity 95 determining region (CDRL) 1 denoted by SEQ ID NO. 216, a CDRL2 denoted by SEQ ID NO. 217, and a CDRL3 denoted by SEQ ID NO. 218; or

1. l. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 219, CDRH2 denoted by SEQ ID NO. 220, CDRH3 denoted by SEQ ID NO. 221, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 222, a CDRL2 denoted by SEQ ID NO. 223, and a CDRL3 denoted by SEQ ID NO. 224; or m. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 225, CDRH2 denoted by SEQ ID NO. 226, CDRH3 denoted by SEQ ID NO. 227, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 228, a CDRL2 denoted by SEQ ID NO. 229, and a CDRL3 denoted by SEQ ID NO. 230; or n. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 231, CDRH2 denoted by SEQ ID NO. 232, CDRH3 denoted by SEQ ID NO. 233, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 234, a CDRL2 denoted by SEQ ID NO. 235, and a CDRL3 denoted by SEQ ID NO. 236; or o. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 237, CDRH2 denoted by SEQ ID NO. 238, CDRH3 denoted by SEQ ID NO. 239, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 240, a CDRL2 denoted by SEQ ID NO. 241, and a CDRL3 denoted by SEQ ID NO. 242; or p. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 243, CDRH2 denoted by SEQ ID NO. 244, CDRH3 denoted by SEQ ID NO. 245, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 246, a CDRL2 denoted by SEQ ID NO. 247, and a CDRL3 denoted by SEQ ID NO. 248; or 96 q. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 249, CDRH2 denoted by SEQ ID NO. 250, CDRH3 denoted by SEQ ID NO. 251, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 252, a CDRL2 denoted by SEQ ID NO. 253, and a CDRL3 denoted by SEQ ID NO. 254; or r. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 255, CDRH2 denoted by SEQ ID NO. 256, CDRH3 denoted by SEQ ID NO. 257, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 258, a CDRL2 denoted by SEQ ID NO. 259, and a CDRL3 denoted by SEQ ID NO. 260; or s. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 261, CDRH2 denoted by SEQ ID NO. 262, CDRH3 denoted by SEQ ID NO. 263, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 264, a CDRL2 denoted by SEQ ID NO. 265, and a CDRL3 denoted by SEQ ID NO. 266; or t. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 267, CDRH2 denoted by SEQ ID NO. 268, CDRH3 denoted by SEQ ID NO. 269, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 270, a CDRL2 denoted by SEQ ID NO. 271, and a CDRL3 denoted by SEQ ID NO. 272; or u. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 273, CDRH2 denoted by SEQ ID NO. 274, CDRH3 denoted by SEQ ID NO. 275, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 276, a CDRL2 denoted by SEQ ID NO. 277, and a CDRL3 denoted by SEQ ID NO. 278; or v. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 279, CDRH2 denoted by SEQ ID NO. 280, CDRH3 denoted by SEQ ID NO. 281, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 282, a CDRL2 97 denoted by SEQ ID NO. 283, and a CDRL3 denoted by SEQ ID NO. 284; or w. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 285, CDRH2 denoted by SEQ ID NO. 286, CDRH3 denoted by SEQ ID NO. 287, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 288, a CDRL2 denoted by SEQ ID NO. 289, and a CDRL3 denoted by SEQ ID NO. 290; or x. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 291, CDRH2 denoted by SEQ ID NO. 292, CDRH3 denoted by SEQ ID NO. 293, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 294, a CDRL2 denoted by SEQ ID NO. 295, and a CDRL3 denoted by SEQ ID NO. 296; or y. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 297, CDRH2 denoted by SEQ ID NO. 298, CDRH3 denoted by SEQ ID NO. 299, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 300, a CDRL2 denoted by SEQ ID NO. 301, and a CDRL3 denoted by SEQ ID NO. 302; or z. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 303, CDRH2 denoted by SEQ ID NO. 304, CDRH3 denoted by SEQ ID NO. 305, and the light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 306, a CDRL2 denoted by SEQ ID NO. 307, and a CDRL3 denoted by SEQ ID NO. 308.

2. The isolated monoclonal antibody according to claim 1, wherein said antibody comprises a heavy chain variable region and a light chain variable region, wherein: a. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 1 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 2; or 98 b. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 3 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 4; or c. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 5 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 6; or d. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 7 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 8; or e. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 9 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 10; or f. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 11 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 12; or g. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 13 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 14; or h. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 15 and wherein said light chain variable region is encoded 99 by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 16; or i. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 81 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 82; or j. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 83 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 84; or k. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 85 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 86; or l. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 87 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 88; or m. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 89 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 90; or n. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 91 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 92; or o. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by 100 SEQ ID NO. 93 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 94; or p. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 95 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 96; or q. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 97 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 98; or r. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 99 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 100; or s. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 101 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 102; or t. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 103 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 104; or u. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 105 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 106; or 101 v. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 107 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 108; or w. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 109 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 110; or x. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 111 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 112; or y. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 113 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 114; or z. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 115 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 116.

3. The isolated monoclonal antibody according to claim 1 or claim 2, wherein said antibody comprises: a. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 17 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 18, or a variant thereof; or b. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 19 or a variant thereof and a light chain variable 102 region comprising the amino acid sequence denoted by SEQ ID NO. 20, or a variant thereof; or c. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 21 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 22, or a variant thereof; or d. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 23 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 24, or a variant thereof; or e. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 25 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 26, or a variant thereof; or f. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 27 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 28, or a variant thereof; or g. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 29 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 30, or a variant thereof; or h. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 31 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 32, or a variant thereof i. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 141 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 142, or a variant thereof; or j. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 143 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 144, or a variant thereof; or 103 k. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 145 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 146, or a variant thereof; or l. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 147 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 148, or a variant thereof; or m. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 149 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 150, or a variant thereof; or n. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 151 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 152, or a variant thereof; or o. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 153 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 154, or a variant thereof; or p. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 155 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 156, or a variant thereof; or q. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 157 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 158, or a variant thereof; or r. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 159 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 160, or a variant thereof; or s. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 161 or a variant thereof and a light chain 104 variable region comprising the amino acid sequence denoted by SEQ ID NO. 162, or a variant thereof; or t. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 163 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 164, or a variant thereof; or u. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 165 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 166, or a variant thereof; or v. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 167 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 168, or a variant thereof; or w. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 169 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 170, or a variant thereof; or x. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 171 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 172, or a variant thereof; or y. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 173 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 174, or a variant thereof; or z. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 175 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 176, or a variant thereof.

4. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein said antibody or antigen-binding fragment thereof binds to at least one of the Receptor binding domain (RBD) or the S1 subunit of the spike protein. 105

5. An isolated monoclonal antibody or antigen-binding fragment thereof which binds to Severe acute respiratory syndrome coronavirus 2 (SARS Cov-2) spike protein, wherein said antibody comprises: a. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 309, CDRH2 denoted by SEQ ID NO. 310, CDRH3 denoted by SEQ ID NO. 311, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 312, a CDRL2 denoted by SEQ ID NO. 313, and a CDRL3 denoted by SEQ ID NO. 314; or b. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 315, CDRH2 denoted by SEQ ID NO. 316, CDRH3 denoted by SEQ ID NO. 317, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 318, a CDRL2 denoted by SEQ ID NO. 319, and a CDRL3 denoted by SEQ ID NO. 320; or c. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 321, CDRH2 denoted by SEQ ID NO. 322, CDRH3 denoted by SEQ ID NO. 323, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 324, a CDRL2 denoted by SEQ ID NO. 325, and a CDRL3 denoted by SEQ ID NO. 326; or d. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 327, CDRH2 denoted by SEQ ID NO. 328, CDRH3 denoted by SEQ ID NO. 329, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 330, a CDRL2 denoted by SEQ ID NO. 331, and a CDRL3 denoted by SEQ ID NO. 332; or e. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 333, CDRH2 denoted by SEQ ID NO. 334, CDRH3 denoted by SEQ ID NO. 335, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 336, a CDRL2 denoted by SEQ ID NO. 337, and a CDRL3 denoted by SEQ ID NO. 338; or 106 f. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 339, CDRH2 denoted by SEQ ID NO. 340, CDRH3 denoted by SEQ ID NO. 341, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 342, a CDRL2 denoted by SEQ ID NO. 343, and a CDRL3 denoted by SEQ ID NO. 344; or g. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 345, CDRH2 denoted by SEQ ID NO. 346, CDRH3 denoted by SEQ ID NO. 347, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 348, a CDRL2 denoted by SEQ ID NO. 349, and a CDRL3 denoted by SEQ ID NO. 350; or h. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 351, CDRH2 denoted by SEQ ID NO. 352, CDRH3 denoted by SEQ ID NO. 353, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 354, a CDRL2 denoted by SEQ ID NO. 355, and a CDRL3 denoted by SEQ ID NO. 356; or i. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 357, CDRH2 denoted by SEQ ID NO. 358, CDRH3 denoted by SEQ ID NO. 359, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 360, a CDRL2 denoted by SEQ ID NO. 361, and a CDRL3 denoted by SEQ ID NO. 362; or j. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 363, CDRH2 denoted by SEQ ID NO. 364, CDRH3 denoted by SEQ ID NO. 365, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 366, a CDRL2 denoted by SEQ ID NO. 367, and a CDRL3 denoted by SEQ ID NO. 368; or k. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 369, CDRH2 denoted by SEQ ID NO. 370, CDRH3 denoted by SEQ ID NO. 371, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 372, a CDRL2 107 denoted by SEQ ID NO. 373, and a CDRL3 denoted by SEQ ID NO. 374; or l. a heavy chain complementarity determining region (CDRH) 1 denoted by SEQ ID NO. 375, CDRH2 denoted by SEQ ID NO. 376, CDRH3 denoted by SEQ ID NO. 377, and a light chain complementarity determining region (CDRL) 1 denoted by SEQ ID NO. 378, a CDRL2 denoted by SEQ ID NO. 379, and a CDRL3 denoted by SEQ ID NO. 380.

6. The isolated monoclonal antibody according to claim 5, wherein said antibody comprises a heavy chain variable region and a light chain variable region, wherein: a. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 117 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 118; or b. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 119 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 120; or c. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 121 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 122; or d. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 123 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 124; or e. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 125 and wherein said light chain variable region is encoded 108 by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 126; or f. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 127 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 128; or g. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 129 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 130; or h. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 131 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 132; or i. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 133 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 134; or j. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 135 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 136; or k. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by SEQ ID NO. 137 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 138; or l. said heavy chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence denoted by 109 SEQ ID NO. 139 and wherein said light chain variable region is encoded by a nucleic acid sequence which is at least 70% identical to SEQ ID NO. 140.

7. The isolated monoclonal antibody according to claim 5 or claim 6, wherein said antibody comprises: a. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 177 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 178, or a variant thereof; or b. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 179 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 180, or a variant thereof; or c. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 181 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 182, or a variant thereof; or d. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 183 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 184, or a variant thereof; or e. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 185 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 186, or a variant thereof; or f. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 187 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 188, or a variant thereof; or g. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 189 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 190, or a variant thereof; or 110 h. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 191 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 192, or a variant thereof; or i. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 193 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 194, or a variant thereof; or j. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 195 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 196, or a variant thereof; or k. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 197 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 198, or a variant thereof; or l. a heavy chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 199 or a variant thereof and a light chain variable region comprising the amino acid sequence denoted by SEQ ID NO. 200.

8. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 5 to 7, wherein said antibody or antigen- binding fragment thereof binds to the N terminal domain (NTD) of the spike protein.

9. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein said antibody or antigen-binding fragment thereof binds the S1 subunit of the spike protein with a K of about 1 pM to about 100 nM. D

10. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein said antibody or antigen-binding fragment thereof inhibits the SARS CoV-2 ability to infect mammalian cells.

11. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein said antibody or 111 antigen-binding fragment thereof is a single-chain Fv-Fc(scFv-Fc) molecule, single-chain Fv (scFv), Fv, heavy chain variable region, light chain variable region, Fab, F(ab) ′ or any combination thereof. 2

12. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-7, wherein said antibody or antigen- binding fragment thereof is a scFv-Fc molecule.

13. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein said antibody is a neutralizing antibody.

14. An isolated nucleic acid molecule comprising a nucleotide sequence encoding an antibody or any antigen-binding fragment thereof according to any one of claims 1-13.

15. An expression vector comprising the isolated nucleic acid molecule according to claim 14.

16. A host cell transfected with the expression vector according to claim 15.

17. An immunoconjugate comprising the antibody or antigen-binding fragment thereof according to any one of claims 1-13 and an additional therapeutic agent.

18. A pharmaceutical composition comprising as an active ingredient at least one isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-13, or immunoconjugate according to claim 17, and a pharmaceutically acceptable carrier, excipient, or diluent.

19. The pharmaceutical composition according to claim 18, wherein said pharmaceutical composition further comprises an additional therapeutic agent.

20. The pharmaceutical composition according to claim 18 or 19, wherein said pharmaceutical composition comprises a combination of at least one antibody directed against the RBD and at least one antibody directed against the NTD of the spike protein of SARS Cov-2.

21. A method of prophylaxis, treatment or amelioration of SARS Cov-2 infection comprising administering to a subject in need thereof a therapeutically effective amount of the isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-13, the 112 immunoconjugate according to claim 17 or the pharmaceutical composition according to any one of claims 18 to 20.

22. The method according to claim 21, wherein said method further comprises administering to a subject in need thereof an additional therapeutic agent.

23. A method of inhibiting the SARS CoV-2 ability to infect mammalian cells in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-13, the immunoconjugate according to claim 17 or the pharmaceutical composition according to any one of claims 18 to 20.

24. The method according to any one of claims 21-23, wherein said isolated monoclonal antibody or antigen-binding fragment thereof, immunoconjugate or said pharmaceutical composition is administered to said subject before or after exposure to SARS CoV-2.

25. A method of detecting SARS Cov-2 in a sample, said method comprising: a. contacting said sample with the isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-13; and b. detecting said isolated monoclonal antibody or any antigen-binding fragment thereof; wherein the presence of said isolated monoclonal antibody or any antigen- binding fragment thereof indicates the presence of SARS Cov-2 in said biological sample.

26. The method of claim 25 wherein said sample is a biological sample obtained from a subject.

27. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-13, the immunoconjugate according to claim 17 or the pharmaceutical composition according to any one of claims 18 to 20 for use in a method of prophylaxis, treatment or amelioration of SARS Cov-2 infection, said method comprising administering to a subject in need thereof a therapeutically effective amount of said isolated monoclonal antibody or antigen-binding fragment thereof, immunoconjugate or said pharmaceutical composition. 113

28. The isolated monoclonal antibody or antigen-binding fragment thereof, or immunoconjugate for use according to claim 27, wherein said method further comprises administering to a subject in need thereof an additional therapeutic agent.

29. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-13, the immunoconjugate according to claim 17 or the pharmaceutical composition according to any one of claims 18 to 20 for use in a method of inhibiting the SARS CoV-2 ability to infect cells in a subject, said method comprising administering to a subject in need thereof a therapeutically effective amount of said isolated monoclonal antibody or antigen-binding fragment thereof, immunoconjugate or said pharmaceutical composition.

30. The isolated monoclonal antibody or antigen-binding fragment thereof, the immunoconjugate or the pharmaceutical composition for use according to any one of claims 27-29, wherein said method comprising administering said isolated monoclonal antibody or antigen-binding fragment thereof, immunoconjugate or said pharmaceutical composition to said subject before or after exposure to SARS CoV-2.

31. A kit for detecting SARS Cov-2 infection comprising: (a) at least one isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-13; (b) means for detection of said isolated monoclonal antibody; and optionally (c) instructions for use of said kit. For the Applicants, REINHOLD COHN AND PARTNERS By: 1 .2 R B D 1 .0 S 1 S 2 0 .8 N T D 0 .6 S P IK E 0 .4 0 .2 0 .0 M D 1 7 M D 2 9 M D 4 5 M D 4 7 M D 6 3 M D 6 5 M D 6 7 Figure 1 M D 1 7 1 0 0 M D 2 9 8 0 M D 4 5 M D 4 7 6 0 M D 6 3 4 0 M D 6 5 M D 6 7 2 0 0 0 .1 1 1 0 1 0 0 A b c o n c e n tra tio n (n M ) Figure 2 1/2 B in d in g (% o f B m a x ) O .D . 4 0 5 n m 1 0 0 5 0 0 M D 1 7 M D 2 9 M D 4 7 Figure 3 BL1 Fc-scFv BL2 Fc-scFv BL3 Fc-scFv BL5 Fc-scFv 100 BL6 Fc-scFv BL7 Fc-scFv 80 BL8 Fc-scFv BL9 Fc-scFv 60 BL10 Fc-scFv BL11 Fc-scFv 40 BL12 Fc-scFv BLK2 Fc-scFv 20 BLK3 Fc-scFv BLK10 Fc-scFv 0 0.01 0.1 1 10 100 BLK14 Fc-scFv Ab concentration ( g/ml) Fig. 4A 100 BLN1 BLN2 80 BLN3 BLN4 60 BLN5 40 BLN7 BLN8 20 BLN9 BLN10 0 0.01 0.1 1 10 100 BLN12 Ab concentration ( g/ml) BLN14 Fig. 4B % Neutralization % o f n e u tra liz a tio Neutralization (%) 2/2 - 1 -