Human monoclonal antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Patent metadata

Field	Value
Publication number	US-11345741-B2
Application number	US-202117212949-A
Country	US
Kind code	B2
Filing date	Mar 25, 2021
Priority date	Mar 26, 2020
Publication date	May 31, 2022
Grant date	May 31, 2022

Abstract

The present disclosure is directed to antibodies binding to and neutralizing the coronavirus designated SARS-CoV-2 and methods for use thereof.

First claim

What is claimed is:

1. An isolated antibody or antibody fragment that binds to a SARS-CoV-2 surface spike protein, wherein the antibody or fragment comprises
(a) a CDRH1 comprising the amino acid sequence of SEQ ID NO:59, a CDRH2 comprising the amino acid sequence of SEQ ID NO:60, a CDRH3 comprising the amino acid sequence of SEQ ID NO:61, a CDRL1 comprising the amino acid sequence of SEQ ID NO:89, a CDRH2 comprising the amino acid sequence of SEQ ID NO:90, a CDRH3 comprising the amino acid sequence of SEQ ID NO:91;
(b) a CDRH1 comprising the amino acid sequence of SEQ ID NO:68, a CDRH2 comprising the amino acid sequence of SEQ ID NO:69, a CDRH3 comprising the amino acid sequence of SEQ ID NO:70, a CDRL1 comprising the amino acid sequence of SEQ ID NO:98, a CDRH2 comprising the amino acid sequence of SEQ ID NO:99, a CDRH3 comprising the amino acid sequence of SEQ ID NO:100;
(c) a CDRH1 comprising the amino acid sequence of SEQ ID NO:41, a CDRH2 comprising the amino acid sequence of SEQ ID NO:42, a CDRH3 comprising the amino acid sequence of SEQ ID NO:43, a CDRL1 comprising the amino acid sequence of SEQ ID NO:71, a CDRH2 comprising the amino acid sequence of SEQ ID NO:72, a CDRH3 comprising the amino acid sequence of SEQ ID NO:73;
(d) a CDRH1 comprising the amino acid sequence of SEQ ID NO:44, a CDRH2 comprising the amino acid sequence of SEQ ID NO:45, a CDRH3 comprising the amino acid sequence of SEQ ID NO:46, a CDRL1 comprising the amino acid sequence of SEQ ID NO:74, a CDRH2 comprising the amino acid sequence of SEQ ID NO:75, a CDRH3 comprising the amino acid sequence of SEQ ID NO:76;
(e) a CDRH1 comprising the amino acid sequence of SEQ ID NO:47, a CDRH2 comprising the amino acid sequence of SEQ ID NO:48, a CDRH3 comprising the amino acid sequence of SEQ ID NO:49, a CDRL1 comprising the amino acid sequence of SEQ ID NO:77, a CDRH2 comprising the amino acid sequence of SEQ ID NO:78, a CDRH3 comprising the amino acid sequence of SEQ ID NO:79;
(f) a CDRH1 comprising the amino acid sequence of SEQ ID NO:50, a CDRH2 comprising the amino acid sequence of SEQ ID NO:51, a CDRH3 comprising the amino acid sequence of SEQ ID NO:52, a CDRL1 comprising the amino acid sequence of SEQ ID NO:80, a CDRH2 comprising the amino acid sequence of SEQ ID NO:81, a CDRH3 comprising the amino acid sequence of SEQ ID NO:82;
(g) a CDRH1 comprising the amino acid sequence of SEQ ID NO:53, a CDRH2 comprising the amino acid sequence of SEQ ID NO:54, a CDRH3 comprising the amino acid sequence of SEQ ID NO:55, a CDRL1 comprising the amino acid sequence of SEQ ID NO:83, a CDRH2 comprising the amino acid sequence of SEQ ID NO:84, a CDRH3 comprising the amino acid sequence of SEQ ID NO:85;
(h) a CDRH1 comprising the amino acid sequence of SEQ ID NO:56, a CDRH2 comprising the amino acid sequence of SEQ ID NO:57 a CDRH3 comprising the amino acid sequence of SEQ ID NO:58, a CDRL1 comprising the amino acid sequence of SEQ ID NO:86, a CDRH2 comprising the amino acid sequence of SEQ ID NO:87, a CDRH3 comprising the amino acid sequence of SEQ ID NO:88;
(i) a CDRH1 comprising the amino acid sequence of SEQ ID NO:62, a CDRH2 comprising the amino acid sequence of SEQ ID NO:63 a CDRH3 comprising the amino acid sequence of SEQ ID NO:64, a CDRL1 comprising the amino acid sequence of SEQ ID NO:65, a CDRH2 comprising the amino acid sequence of SEQ ID NO:66, a CDRH3 comprising the amino acid sequence of SEQ ID NO:67; or
(j) a CDRH1 comprising the amino acid sequence of SEQ ID NO:65, a CDRH2 comprising the amino acid sequence of SEQ ID NO:66, a CDRH3 comprising the amino acid sequence of SEQ ID NO:67, a CDRL1 comprising the amino acid sequence of SEQ ID NO:95, a CDRH2 comprising the amino acid sequence of SEQ ID NO:96, a CDRH3 comprising the amino acid sequence of SEQ ID NO:97.

2. The antibody or antibody fragment of claim 1 , wherein the antibody or fragment comprises
(a) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:33 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:34;
(b) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:39 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:40;
(c) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:21 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:22;
(d) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:23 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:24;
(e) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:25 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:26;
(f) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:27 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:28;
(g) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:29 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:30;
(h) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:31 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:32;
(i) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:35 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:36; or
(j) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO:37 and/or a light chain variable sequence comprising the amino acid sequence of SEQ ID NO:38.

3. The antibody or antibody fragment of claim 1 , wherein the antibody or fragment is monoclonal.

4. The antibody or antibody fragment of claim 1 , wherein the antibody or fragment comprises a YTE mutation.

5. The antibody or antibody fragment of claim 1 , wherein the antibody or fragment is an IgG.

6. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment is able to bind RBD in the “up” and “down” conformations.

7. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment is able to bind RBD in the “up” conformation and is not able to bind RBD in the “down” conformation.

8. The antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment further comprises a detectable label.

9. A vaccine formulation comprising the antibody or antibody fragment of claim 1 .

10. The vaccine formulation of claim 9 , further comprising a second antibody or antibody fragment that binds to a SARS-CoV-2 surface spike protein.

11. A pharmaceutically acceptable composition or kit comprising a first antibody or antibody fragment that binds to a SARS-CoV-2 surface spike protein and a second antibody or antibody fragment that binds to a SAR-CoV-2 surface spike protein, wherein the first antibody or antibody fragment comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO:59, a CDRH2 comprising the amino acid sequence of SEQ ID NO:60, a CDRH3 comprising the amino acid sequence of SEQ ID NO:61, a CDRL1 comprising the amino acid sequence of SEQ ID NO:89, a CDRH2 comprising the amino acid sequence of SEQ ID NO:90, a CDRH3 comprising the amino acid sequence of SEQ ID NO:91, and wherein the second antibody or antibody fragment comprises a CDRH1 comprising the amino acid sequence of SEQ ID NO:68, a CDRH2 comprising the amino acid sequence of SEQ ID NO:69, a CDRH3 comprising the amino acid sequence of SEQ ID NO:70, a CDRL1 comprising the amino acid sequence of SEQ ID NO:98, a CDRH2 comprising the amino acid sequence of SEQ ID NO:99, a CDRH3 comprising the amino

Assignees

• Univ Vanderbilt

Inventors

• Crowe Jr James E
• Zost Seth
• Carnahan Robert
• Gilchuk Pavlo

Classifications

• C07K16/104 Primary

  Severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2] · CPC title

• C07K16/102

  Coronaviridae (F) · CPC title

• G01N2333/165

  Coronaviridae, e.g. avian infectious bronchitis virus · CPC title

• G01N33/56983 Primary

  Viruses · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title