VARIANT NUCLEIC ACID LIBRARIES FOR CORONAVIRUS
Provided herein are methods and compositions relating to libraries of optimized antibodies having nucleic acids encoding for an antibody comprising modified sequences. Libraries described herein comprise nucleic acids encoding SARS-CoV-2 or ACE2 antibodies. Further described herein are protein libraries generated when the nucleic acid libraries are translated. Further described herein are cell libraries expressing variegated nucleic acid libraries described herein.
1 . An antibody or antibody fragment comprising a variable domain, heavy chain region (VH) and a variable domain, light chain region (VL), wherein VH comprises complementarity determining regions CDRH1, CDRH2, and CDRH3, wherein VL comprises complementarity determining regions CDRL1, CDRL2, and CDRL3, and wherein (a) an amino acid sequence of CDRH1 is as set forth in any one of SEQ ID NOs: 1-36 or 217-282; (b) an amino acid sequence of CDRH2 is as set forth in any one of SEQ ID NOs: 37-72 or 283-348; (c) an amino acid sequence of CDRH3 is as set forth in any one of SEQ ID NOs: 73-108 or 349-414; (d) an amino acid sequence of CDRL1 is as set forth in any one of SEQ ID NOs: 109-144 or 415-473; (e) an amino acid sequence of CDRL2 is as set forth in any one of SEQ ID NOs: 145-180 or 415-473; and (f) an amino acid sequence of CDRL3 is as set forth in any one of SEQ ID NOs: 181-216 or 533-591.
2 . The antibody or antibody fragment of claim 1 , wherein (a) an amino acid sequence of CDRH1 is as set forth in SEQ ID NO: 30; (b) an amino acid sequence of CDRH2 is as set forth in SEQ ID NO: 66; (c) an amino acid sequence of CDRH3 is as set forth in SEQ ID NO: 102; (d) an amino acid sequence of CDRL1 is as set forth in SEQ ID NO: 138; (e) an amino acid sequence of CDRL2 is as set forth in SEQ ID NO: 174; and (f) an amino acid sequence of CDRL3 is as set forth in SEQ ID NO: 210.
3 . The antibody or antibody fragment of claim 1 , wherein (a) an amino acid sequence of CDRH1 is as set forth in SEQ ID NO: 35; (b) an amino acid sequence of CDRH2 is as set forth in SEQ ID NO: 71; (c) an amino acid sequence of CDRH3 is as set forth in SEQ ID NO: 107; (d) an amino acid sequence of CDRL1 is as set forth in SEQ ID NO: 143; (e) an amino acid sequence of CDRL2 is as set forth in SEQ ID NO: 179; and (f) an amino acid sequence of CDRL3 is as set forth in SEQ ID NO: 215.
4 . The antibody or antibody fragment of claim 1 , wherein (a) an amino acid sequence of CDRH1 is as set forth in SEQ ID NO: 12; (b) an amino acid sequence of CDRH2 is as set forth in SEQ ID NO: 48; (c) an amino acid sequence of CDRH3 is as set forth in SEQ ID NO: 84; (d) an amino acid sequence of CDRL1 is as set forth in SEQ ID NO: 120; (e) an amino acid sequence of CDRL2 is as set forth in SEQ ID NO: 156; and (f) an amino acid sequence of CDRL3 is as set forth in SEQ ID NO: 192.
5 . The antibody or antibody fragment of claim 1 , wherein (a) an amino acid sequence of CDRH1 is as set forth in SEQ ID NO: 31; (b) an amino acid sequence of CDRH2 is as set forth in SEQ ID NO: 67; (c) an amino acid sequence of CDRH3 is as set forth in SEQ ID NO: 103; (d) an amino acid sequence of CDRL1 is as set forth in SEQ ID NO: 139; (e) an amino acid sequence of CDRL2 is as set forth in SEQ ID NO: 175; and (f) an amino acid sequence of CDRL3 is as set forth in SEQ ID NO: 211.
6 . The antibody or antibody fragment of claim 1 , wherein (a) an amino acid sequence of CDRH1 is as set forth in SEQ ID NO: 240; (b) an amino acid sequence of CDRH2 is as set forth in SEQ ID NO: 306; (c) an amino acid sequence of CDRH3 is as set forth in SEQ ID NO: 372; (d) an amino acid sequence of CDRL1 is as set forth in SEQ ID NO: 437; (e) an amino acid sequence of CDRL2 is as set forth in SEQ ID NO: 496; and (f) an amino acid sequence of CDRL3 is as set forth in SEQ ID NO: 555.
7 . The antibody or antibody fragment of claim 1 , wherein (a) an amino acid sequence of CDRH1 is as set forth in SEQ ID NO: 244; (b) an amino acid sequence of CDRH2 is as set forth in SEQ ID NO: 310; (c) an amino acid sequence of CDRH3 is as set forth in SEQ ID NO: 376; (d) an amino acid sequence of CDRL1 is as set forth in SEQ ID NO: 437; (e) an amino acid sequence of CDRL2 is as set forth in SEQ ID NO: 496; and (f) an amino acid sequence of CDRL3 is as set forth in SEQ ID NO: 555.
8 . The antibody or antibody fragment of claim 1 , wherein (a) an amino acid sequence of CDRH1 is as set forth in SEQ ID NO: 270; (b) an amino acid sequence of CDRH2 is as set forth in SEQ ID NO: 336; (c) an amino acid sequence of CDRH3 is as set forth in SEQ ID NO: 402; (d) an amino acid sequence of CDRL1 is as set forth in SEQ ID NO: 461; (e) an amino acid sequence of CDRL2 is as set forth in SEQ ID NO: 520; and (f) an amino acid sequence of CDRL3 is as set forth in SEQ ID NO: 579.
9 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment binds to a spike glycoprotein.
10 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment binds to a receptor binding domain of the spike glycoprotein.
11 . (canceled)
12 . (canceled)
13 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises a K D of less than 10 nM.
14 . The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises a K D of less than 5 nM.
15 . An antibody or antibody fragment comprising a variable domain, heavy chain region (VH) and a variable domain, light chain region (VL), wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as set forth in any one of SEQ ID NOs: 592-657, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as set forth in any one of SEQ ID NOs: 658-716.
16 . The antibody or antibody fragment of claim 15 , wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 594, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 660.
17 . The antibody or antibody fragment of claim 15 , wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 595, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 661.
18 . The antibody or antibody fragment of claim 15 , wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 598, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 664.
19 . The antibody or antibody fragment of claim 15 , wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 603, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 669.
20 . The antibody or antibody fragment of claim 15 , wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 615, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 680.
21 . The antibody or antibody fragment of claim 15 , wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 631, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 691.
22 . The antibody or antibody fragment of claim 15 , wherein the VH comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 645, and wherein the VL comprises an amino acid sequence at least about 90% identical to a sequence as set forth in SEQ ID NO: 704.
23 .- 47 . (canceled)