WO2023019174A4 - Antibodies to sars-cov-2 - Google Patents

Antibodies to sars-cov-2 Download PDF

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Publication number
WO2023019174A4
WO2023019174A4 PCT/US2022/074769 US2022074769W WO2023019174A4 WO 2023019174 A4 WO2023019174 A4 WO 2023019174A4 US 2022074769 W US2022074769 W US 2022074769W WO 2023019174 A4 WO2023019174 A4 WO 2023019174A4
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seq
nos
amino acid
acid sequence
variable region
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PCT/US2022/074769
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French (fr)
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WO2023019174A3 (en
WO2023019174A2 (en
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John Paul Alderete
Robin J. HELLEN
Kathleen Anne KENNEDY
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Apollos Diagnostics, Llc
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Publication of WO2023019174A3 publication Critical patent/WO2023019174A3/en
Publication of WO2023019174A4 publication Critical patent/WO2023019174A4/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
    • C07K16/1002Coronaviridae
    • C07K16/1003Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2 or Covid-19]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Virology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pulmonology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the 2019-20 coronavirus pandemic, has infected humans around the world, causing the coronavirus disease 2019 (COVID-19).The disclosure provides for certain monoclonal antibodies and/or antigen-binding fragments that selectively bind to a coronavirus protein, and more specifically, selectively binds to a protein of SARS-Co V-2 and its variant strains, and methods of use of the disclosed antibodies and antigen-binding fragments.

Claims

AMENDED CLAIMS received by the International Bureau on 7 July 2023 (07.07.2023) What is claimed is:
1. A monoclonal antibody that selectively binds to a nucleocapsid protein, an envelope protein, a membrane protein, or a spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) comprising a heavy chain complementarity determining region 1 (CDR1) region, a heavy chain CDR2 region, and a heavy chain CDR3 region, wherein the heavy chain CDR1 region, the heavy chain CDR2 region, and the heavy chain CDR3 region comprise amino acid sequences of: a) SEQ ID NOS: 15, 65, and 115, respectively b) SEQ ID NOS: 17, 67, and 117, respectively; c) SEQ ID NOS: 5, 55, and 105, respectively; d) SEQ ID NOS: 7, 57, and 107, respectively; e) SEQ ID NOS: 9, 59, and 109, respectively; f) SEQ ID NOS: 11, 61, and 111, respectively; g) SEQ ID NOS: 13, 63, and 113, respectively; h) SEQ ID NOS: 1, 51, and 101, respectively; i) SEQ ID NOS: 3, 53, and 103, respectively; j) SEQ ID NOS: 19, 69, and 119, respectively; k) SEQ ID NOS: 20, 70, and 120, respectively; l) SEQ ID NOS: 23, 73, and 123, respectively; m) SEQ ID NOS: 26, 76, and 126, respectively; n) SEQ ID NOS: 28, 78, and 128, respectively; o) SEQ ID NOS: 30, 80, and 130, respectively; p) SEQ ID NOS: 32, 82, and 132, respectively; q) SEQ ID NOS: 35, 85, and 135, respectively; r) SEQ ID NOS: 37, 87, and 137, respectively; s) SEQ ID NOS: 39, 89, and 139, respectively, t) SEQ ID NOS: 41, 91, and 141, respectively; u) SEQ ID NOS: 43, 93, and 143, respectively; v) SEQ ID NOS: 45, 95, and 145, respectively; w) SEQ ID NOS: 47, 97, and 147, respectively; or x) SEQ ID NOS: 49, 99, and 149, respectively; and the monoclonal antibody comprising a light chain CDR1 region, a light chain CDR2 region, and a light chain CDR3 region, wherein the light chain CDR1 region, the light chain CDR2 region, and the light chain CDR3 region comprise amino acid sequences of: aa) SEQ ID NOS: 16, 66, and 116, respectively; bb) SEQ ID NOS: 18, 68, and 118, respectively; cc) SEQ ID NOS: 6, 56, and 106, respectively; dd) SEQ ID NOS: 8, 58, and 108, respectively; ee) SEQ ID NOS: 10, 60, and 110, respectively; ff) SEQ ID NOS: 12, 62, and 112, respectively; gg) SEQ ID NOS: 14, 64, and 114, respectively; hh) SEQ ID NOS: 2, 52, and 102, respectively; ii) SEQ ID NOS: 4, 54, and 104, respectively; jj) SEQ ID NOS: 21, 71, and 121, respectively; kk) SEQ ID NOS: 22, 72, and 122, respectively;
11) SEQ ID NOS: 24, 74, and 124, respectively; mm) SEQ ID NOS: 25, 75, and 125, respectively; nn) SEQ ID NOS: 27, 77, and 127, respectively; oo) SEQ ID NOS: 29, 79, and 129, respectively; pp) SEQ ID NOS: 31, 81, and 131, respectively; qq) SEQ ID NOS: 33, 83, and 133, respectively; rr) SEQ ID NOS: 34, 84, and 134, respectively; ss) SEQ ID NOS: 36, 86, and 136, respectively; tt) SEQ ID NOS: 38, 88, and 138, respectively; uu) SEQ ID NOS: 40, 90, and 140, respectively; w) SEQ ID NOS: 42, 92, and 142, respectively; ww) SEQ ID NOS: 44, 94, and 144, respectively; xx) SEQ ID NOS: 46, 96, and 146, respectively; yy) SEQ ID NOS: 48, 98, and 148, respectively; or zz) SEQ ID NOS: 50, 100, and 150, respectively.
63
2. The monoclonal antibody of claim 1, wherein the heavy chain CDR1 region, the heavy chain CDR2 region, and the heavy chain CDR3 region comprise amino acid sequences of: a) SEQ ID NOS: 15, 65, and 115, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 165; b) SEQ ID NOS: 17, 67, and 117, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 167; c) SEQ ID NOS: 5, 55, and 105, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 155; d) SEQ ID NOS: 7, 57, and 107, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 157; e) SEQ ID NOS: 9, 59, and 109, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 159; f) SEQ ID NOS: 11, 61, and 111, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 161; g) SEQ ID NOS: 13, 63, and 113, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 163; h) SEQ ID NOS: 1, 51, and 101, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 151; i) SEQ ID NOS: 3, 53, and 103, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 153; j) SEQ ID NOS: 19, 69, and 119, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 169; k) SEQ ID NOS: 20, 70, and 120, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 170; l) SEQ ID NOS: 23, 73, and 123, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 173; m) SEQ ID NOS: 26, 76, and 126, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 176; n) SEQ ID NOS: 28, 78, and 128, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 178;
64 o) SEQ ID NOS: 30, 80, and 130, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 180 p) SEQ ID NOS: 32, 82, and 132, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 182; q) SEQ ID NOS: 35, 85, and 135, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 185; r) SEQ ID NOS: 37, 87, and 137, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 187; s) SEQ ID NOS: 39, 89, and 139, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 189; t) SEQ ID NOS: 41, 91, and 141, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 191; u) SEQ ID NOS: 43, 93, and 143, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 193; v) SEQ ID NOS: 45, 95, and 145, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 195; w) SEQ ID NOS: 47, 97, and 147, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 197; or x) SEQ ID NOS: 49, 99, and 149, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 199.
3. The monoclonal antibody or antigen-binding fragment of claim 1, wherein the light chain CDR1 region, the light chain CDR2 region, and the light chain CDR3 region comprise amino acid sequences of: a) SEQ ID NOS: 16, 66, and 116, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 166; b) SEQ ID NOS: 18, 68, and 118, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 168; c) SEQ ID NOS: 6, 56, and 106, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 156;
65 d) SEQ ID NOS: 8, 58, and 108, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 158; e) SEQ ID NOS: 10, 60, and 110, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 160; f) SEQ ID NOS: 12, 62, and 112, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 162; g) SEQ ID NOS: 14, 64, and 114, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 164; h) SEQ ID NOS: 2, 52, and 102, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 152; i) SEQ ID NOS: 4, 54, and 104, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 154; jj) SEQ ID NOS: 21, 71, and 121, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 171; kk) SEQ ID NOS: 22, 72, and 122, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 172; 11) SEQ ID NOS: 24, 74, and 124, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 174; mm) SEQ ID NOS: 25, 75, and 125, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 175; nn) SEQ ID NOS: 27, 77, and 127, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 177; oo) SEQ ID NOS: 29, 79, and 129, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 179; pp) SEQ ID NOS: 31, 81, and 131, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 181; qq) SEQ ID NOS: 33, 83, and 133, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 183; rr) SEQ ID NOS: 34, 84, and 134, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 184;
66 ss) SEQ ID NOS: 36, 86, and 136, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 186; tt) SEQ ID NOS: 38, 88, and 138, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 188; uu) SEQ ID NOS: 40, 90, and 140, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 190; w) SEQ ID NOS: 42, 92, and 142, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 192; ww) SEQ ID NOS: 44, 94, and 144, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 194; xx) SEQ ID NOS: 46, 96, and 146, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 196; yy) SEQ ID NOS: 48, 98, and 148, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 198; or zz) SEQ ID NOS: 50, 100, and 150, respectively, and further comprising a variable region sequence having an amino acid sequence at least 95% identical to SEQ ID NO: 200.
4. The monoclonal antibody of claim 1, further comprising a variable heavy chain region and a variable light chain region, wherein each of the variable heavy chain region and the variable light chain region comprises: a) SEQ ID NOS: 165 and 166, respectively; b) SEQ ID NOS: 167 and 168, respectively; c) SEQ ID NOS: 155 and 156, respectively; d) SEQ ID NOS: 157 and 158, respectively; e) SEQ ID NOS: 159 and 160, respectively; f) SEQ ID NOS: 161 and 162, respectively; g) SEQ ID NOS: 163 and 164, respectively; h) SEQ ID NOS: 151 and 152, respectively; i) SEQ ID NOS: 153 and 154, respectively; j) SEQ ID NOS: 169 and 171, respectively; k) SEQ ID NOS: 169 and 172, respectively; l) SEQ ID NOS: 170 and 171, respectively; m) SEQ ID NOS: 170 and 172, respectively; n) SEQ ID NOS: 173 and 174, respectively; o) SEQ ID NOS: 176 and 177, respectively; p) SEQ ID NOS: 178 and 179, respectively; q) SEQ ID NOS: 180 and 181, respectively; r) SEQ ID NOS: 182 and 183, respectively; s) SEQ ID NOS: 182 and 184, respectively; t) SEQ ID NOS: 185 and 186, respectively; u) SEQ ID NOS: 187 and 188, respectively; v) SEQ ID NOS: 189 and 190, respectively; w) SEQ ID NOS: 191 and 192, respectively; x) SEQ ID NOS: 193 and 194, respectively; y) SEQ ID NOS: 195 and 196, respectively; z) SEQ ID NOS: 197 and 198, respectively; or aa) SEQ ID NOS: 199 and 200, respectively.
5. The monoclonal antibody of claim 1, further comprising a heavy chain and a light chain, wherein the heavy chain and the light chain each comprise an amino acid sequence comprising: a) SEQ ID NOS: 215 and 216, respectively; b) SEQ ID NOS: 217 and 218, respectively; c) SEQ ID NOS: 205 and 206, respectively; d) SEQ ID NOS: 207 and 208, respectively; e) SEQ ID NOS: 209 and 210, respectively; f) SEQ ID NOS: 211 and 212, respectively; g) SEQ ID NOS: 213 and 214, respectively; h) SEQ ID NOS: 201 and 202, respectively; or i) SEQ ID NOS: 203 and 204, respectively.
6. The monoclonal antibody of claim 1, wherein the monoclonal antibody is a mouse antibody, human antibody, or a chimeric or humanized antibody.
7. The monoclonal antibody of claim 1, wherein the antibody is an IgG, an IgM, an IgE, an IgA, or an IgD, or is derived therefrom.
8. The monoclonal antibody of claim 1, wherein the antigen-binding fragment comprises a Fab, a Fab', a F(ab')2, a variable fragment (Fv), a triabody, a tetrabody, a minibody, a bispecific F(ab')2, a trispecific F(ab')2, a diabody, a bispecific diabody, a single chain variable fragment (scFv), a scFv-Fc, a Fab-Fc, a VHH, or a bispecific scFv.
9. The monoclonal antibody or antigen-binding fragment of claim 1 wherein the monoclonal antibody or antigen-binding fragment has a binding affinity of less than 100 nanomolar for the nucleocapsid protein, the envelope protein, the membrane protein, or the spike protein.
10. The monoclonal antibody or antigen-binding fragment of claim 9 wherein the monoclonal antibody specifically binds to the nucleocapsid protein.
11. A composition comprising the monoclonal antibody of any one of claims 1-10, and pharmaceutically acceptable carrier.
12. A method of treating a SARS-CoV-2 viral infection or CO VID-19 disease in a subject in need thereof, comprising administering to the subject an effective amount of the composition of claim 11.
13. The method of claim 12, further comprising administering one or more additional anti-viral agents to the subject.
14. A method of detecting SARS-CoV-2 virus comprising:
69 contacting a sample obtained from a subject suspected of having the SARS-CoV-2 virus with the antibody of any one of claims 1-10; detecting the presence or absence of an antibody/SARS-CoV-2 virus complex, wherein the detection of the antibody/SARS-CoV-2 virus complex or the antigen-binding fragment/SARS- CoV-2 virus complex indicates an active infection.
15. The method of claim 14, wherein the sample comprises a nasal swab, a tissue sample, saliva, or blood.
16. A polynucleotide encoding a variable heavy chain region and a variable light chain region, wherein the variable heavy chain region comprises the DNA sequence of any one of SEQ ID NOS: 233, 235, 219, 221, 223, 225, 227, 229, 231, 237, 238, 241, 244, 246, 248, 250, 253, 255, 257, 259, 261, 263, 265, and 267; and the variable light chain region comprises the DNA sequence of any one of SEQ ID NOS: 234, 236, 220, 222, 224, 226, 228, 230, 232, 239, 240, 242, 243, 245, 247, 249, 251, 252, 254, 256, 258, 260, 262, 264, 266, and 268.
17. The polynucleotide of claim 16, wherein the polynucleotide encoding a variable heavy chain region and a variable light chain region comprising: a) SEQ ID NO: 237 and SEQ ID NO: 239, respectively; b) SEQ ID NO: 237 and SEQ ID NO: 240, respectively; c) SEQ ID NO: 238 and SEQ ID NO: 239, respectively; d) SEQ ID NO: 238 and SEQ ID NO: 240, respectively; e) SEQ ID NO: 238 and SEQ ID NO: 240, respectively; f) SEQ ID NO: 241 and SEQ ID NO: 242, respectively; g) SEQ ID NO: 241 and SEQ ID NO: 243, respectively; h) SEQ ID NO: 244 and SEQ ID NO: 245, respectively; i) SEQ ID NO: 246 and SEQ ID NO: 247, respectively; j) SEQ ID NO: 248 and SEQ ID NO: 249, respectively; k) SEQ ID NO: 250 and SEQ ID NO: 251, respectively; l) SEQ ID NO: 250 and SEQ ID NO: 252, respectively; m) SEQ ID NO: 253 and SEQ ID NO: 254, respectively;
70 n) SEQ ID NO: 255 and SEQ ID NO: 256, respectively; o) SEQ ID NO: 257 and SEQ ID NO: 258, respectively; p) SEQ ID NO: 259 and SEQ ID NO: 260, respectively; q) SEQ ID NO: 261 and SEQ ID NO: 262, respectively; r) SEQ ID NO: 263 and SEQ ID NO: 264, respectively; s) SEQ ID NO: 265 and SEQ ID NO: 266, respectively; or t) SEQ ID NO: 267 and SEQ ID NO: 268, respectively.
18. A polynucleotide encoding a heavy chain comprising the DNA sequence of any one of SEQ ID NOS: 233, 235, 219, 221, 223, 225, 227, 229, and 231; and a light chain comprising a DNA sequence of any one of SEQ ID NOS: 234, 236, 220, 222, 224, 226, 228, 230, and 232.
19. The polynucleotide of claim 18, wherein a heavy chain and a light chain comprises: a) SEQ ID NO: 233 and SEQ ID NO: 234, respectively; b) SEQ ID NO: 235 and SEQ ID NO: 236, respectively; c) SEQ ID NO: 223 and SEQ ID NO: 224, respectively; d) SEQ ID NO: 225 and SEQ ID NO: 226, respectively; e) SEQ ID NO: 227 and SEQ ID NO: 228, respectively; f) SEQ ID NO: 229 and SEQ ID NO: 230, respectively; g) SEQ ID NO: 231 and SEQ ID NO: 232, respectively; h) SEQ ID NO: 219 and SEQ ID NO: 220, respectively; or i) SEQ ID NO: 221 and SEQ ID NO: 222, respectively.
20. A recombinant cell comprising the polynucleotide of any one of claims 16-19.
71
PCT/US2022/074769 2021-08-11 2022-08-10 Antibodies to sars-cov-2 WO2023019174A2 (en)

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