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Anti-sars-cov-2 Antibodies
| Content Provider | The Lens |
|---|---|
| Description | La présente invention concerne des anticorps monoclonaux isolés qui se lient à la protéine spike du coronavirus du syndrome respiratoire aigu sévère de type 2 (SRAS-CoV-2), et leurs utilisations pour le traitement de la COVID-19. |
| Abstract | The present invention is directed to isolated monoclonal antibodies which binds to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, and to uses thereof for treating COVID-19. |
| Related Links | https://www.lens.org/lens/patent/183-596-641-610-850/frontpage |
| Language | English |
| Publisher Date | 2021-11-18 |
| Access Restriction | Open |
| Alternative Title | Anticorps Anti-sars-cov-2 |
| Content Type | Text |
| Resource Type | Patent |
| Date Applied | 2021-03-25 |
| Agent | Lotan, Mirit |
| Applicant | The Israel Institute of Biological Res Iibr |
| Application No. | 2021050335 |
| Claim | 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. 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 b. 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 c. 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 d. 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 e. 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 f. 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 g. 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 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 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. 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. 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 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. 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 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. 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 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. 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 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. 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 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. 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 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. 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 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 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. Ill 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. 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. 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 b. 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 c. 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 d. 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 e. 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 f. 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 g. 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 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 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 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. 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 SI subunit of the spike protein. 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 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. 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 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. 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 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. 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 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 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. 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. 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 S 1 subunit of the spike protein with a KD of about 1 pM to about 100 nM. 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. 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 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)2' or any combination thereof. 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. The isolated monoclonal antibody or antigen-binding fragment thereof according to any one of the preceding claims, wherein said antibody is a neutralizing antibody. 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. An expression vector comprising the isolated nucleic acid molecule according to claim 14. A host cell transfected with the expression vector according to claim 15. An immunoconjugate comprising the antibody or antigen-binding fragment thereof according to any one of claims 1-13 and an additional therapeutic agent. 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. The pharmaceutical composition according to claim 18, wherein said pharmaceutical composition further comprises an additional therapeutic agent. 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. 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 immunoconjugate according to claim 17 or the pharmaceutical composition according to any one of claims 18 to 20. The method according to claim 21, wherein said method further comprises administering to a subject in need thereof an additional therapeutic agent. 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. 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. The method according to any one of claims 21-24 wherein said SARS-CoV-2 is a SARS-CoV-2 variant. The method according to claim 25 wherein said SARS-CoV-2 variant is selected from a group consisting of the B.1.7 variant, the P.l variant, and the B.1.351 variant (also termed the 501Y.V2 variant). A method of detecting SARS-CoV-2 in a sample, said method comprising: a. contacting said sample with at least one isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-13; and b. detecting said at least one isolated monoclonal antibody or any antigenbinding fragment thereof; wherein the presence of said isolated monoclonal antibody or any antigenbinding fragment thereof indicates the presence of SARS-CoV-2 in said biological sample. A method of detecting SARS-CoV-2 in a sample, said method comprising: a. immobilizing at least one isolated monoclonal antibody or antigen-binding fragment thereof according to any one of claims 1-13 (the "capture antibody") onto a substrate, wherein said substrate is placed in a vessel; b. contacting said capture antibody with said sample; and c. adding to said vessel at least one isolated monoclonal antibody or antigenbinding fragment thereof of the invention (the "reporter antibody"), wherein said at least one reporter antibody is different from said at least one capture antibody, and wherein said reporter antibody is optionally detectably labelled; wherein detecting the presence of said at least one reporter antibody indicates the presence of SARS-CoV-2 SARS-CoV-2spike protein in said sample. The method of claim 28 wherein said at least one reporter antibody is a biotinylated antibody or is being associated with a detectable molecule (e.g., a fluorophore or an enzyme such as horse radish peroxidase or alkaline phosphatase). The method of any one of claims 27-29 wherein said sample is a biological sample obtained from a subject. The method of claim 30 wherein said subject is a symptomatic or an asymptomatic subject. The method of any one of claims 27-31 wherein said SARS-CoV-2 is a SARS- CoV-2 variant. The method of claim 32 wherein said SARS-CoV-2 variant is selected from a group consisting of the B.1.1.7 variant, the P.1 variant, and the B.1.351 variant (also termed the 501 Y.V2 variant). 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. The isolated monoclonal antibody or antigen-binding fragment thereof, or immunoconjugate for use according to claim 32, wherein said method further comprises administering to a subject in need thereof an additional therapeutic agent. 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. The isolated monoclonal antibody or antigen-binding fragment thereof, the immunoconjugate or the pharmaceutical composition for use according to any one of claims 34-36, 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. 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. |
| CPC Classification | Preparations For Medical; Dental Or Toiletry Purposes PEPTIDES Investigating Or Analysing Materials By Determining Their Chemical Or Physical Properties |
| Extended Family | 014-893-253-199-839 183-596-641-610-850 036-637-879-211-524 |
| Patent ID | 2021229561 |
| Inventor/Author | Noy-porat Tal Mechaly Adva Makdasi Efi Rosenfeld Ronit Mazor Ohad |
| IPC | C07K16/10 A61K39/395 A61P11/00 A61P31/14 G01N33/68 |
| Status | Pending |
| Simple Family | 183-596-641-610-850 |
| CPC (with Group) | A61K2039/505 A61K2039/507 C07K2317/52 C07K2317/622 C07K2317/72 C07K2317/76 G01N33/56983 G01N2333/165 G01N2469/10 C07K16/1003 |
| Issuing Authority | World Intellectual Property Organization (WIPO) |
| Kind | Patent Application Publication |
