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CN-122029189-A - Anti-SARS-CoV-2 spike (S) antibodies and their use in treatment COVID-19

CN122029189ACN 122029189 ACN122029189 ACN 122029189ACN-122029189-A

Abstract

The present invention provides antibodies that bind to SARS-CoV-2 spike (S) protein. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions and methods using the above antibodies that bind to the SARS-CoV-2 spike (S) protein.

Inventors

  • G. SMITH
  • N. PATEL

Assignees

  • 诺瓦瓦克斯股份有限公司

Dates

Publication Date
20260512
Application Date
20240928
Priority Date
20230928

Claims (20)

  1. 1. An antibody or fragment thereof that binds to a sudden acute respiratory syndrome coronavirus 2 (CoV) spike (S) glycoprotein, wherein the antibody or fragment thereof comprises: (i) A variable light chain complementarity determining region 1 (VL CDR 1) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 9, 12, 15 and 18; (ii) Variable light chain complementarity determining region 2 (VL CDR 2) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 10, 13, 16 and 19; (iii) A variable light chain complementarity determining region 3 (VL CDR 3) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 11, 14, 17 and 20; (iv) Variable heavy chain complementarity determining region 1 (VH CDR 1) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 21, 24, 27 and 30; (v) A variable heavy chain complementarity determining region 2 (VH CDR 2) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 22, 25, 28 and 31, and (Vi) Variable heavy chain complementarity determining region 3 (VH CDR 3) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 23, 26, 29 and 32.
  2. 2. An antibody or fragment thereof that binds to the spike (S) protein of sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2), wherein the antibody or fragment thereof comprises: (i) A variable heavy chain (VH) domain comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a polypeptide of any one of SEQ ID NOs 5-8, and (Ii) A variable light chain (VL) domain comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a polypeptide of any one of SEQ ID NOs 1-4.
  3. 3. The antibody or fragment thereof of claim 1, wherein the antibody or fragment thereof comprises: (i) A variable heavy chain (VH) domain comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a polypeptide of any one of SEQ ID NOs 5-8, and (Ii) A variable light chain (VL) domain comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a polypeptide of any one of SEQ ID NOs 1-4.
  4. 4. The antibody or fragment thereof of claim 2, wherein the antibody or fragment thereof comprises: ((i) a variable light chain complementarity determining region 1 (VL CDR 1) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 9, 12, 15 and 18; (ii) Variable light chain complementarity determining region 2 (VL CDR 2) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 10, 13, 16 and 19; (iii) A variable light chain complementarity determining region 3 (VL CDR 3) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 11, 14, 17 and 20; (iv) Variable heavy chain complementarity determining region 1 (VH CDR 1) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 21, 24, 27 and 30; (v) A variable heavy chain complementarity determining region 2 (VH CDR 2) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 22, 25, 28 and 31, and (Vi) Variable heavy chain complementarity determining region 3 (VH CDR 3) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 23, 26, 29 and 32.
  5. 5. The antibody or fragment thereof of claims 1 to 4, wherein the antibody or fragment thereof is selected from the group consisting of VH CDR1 according to any one of SEQ ID NOs 21, 24, 27 and 30, VH CDR2 according to any one of SEQ ID NOs 22, 25, 28 and 31, VH CDR3 according to any one of SEQ ID NOs 23, 26, 29 and 32, VL CDR1 according to any one of SEQ ID NOs 9, 12, 15 and 18, VL CDR2 according to any one of SEQ ID NOs 10, 13, 16 and 19, and VL CDR3 according to any one of SEQ ID NOs 11, 14, 17 and 20.
  6. 6. The antibody or fragment thereof according to any one of claims 1 to 4, wherein the antibody or fragment thereof comprises a VH CDR1 according to SEQ ID NO. 21, a VH CDR2 according to SEQ ID NO. 22 and a VH CDR3 according to SEQ ID NO. 23, a VL CDR1 according to SEQ ID NO. 9, a VL CDR2 according to SEQ ID NO. 10, and a VL CDR3 according to SEQ ID NO. 11.
  7. 7. The antibody or fragment thereof of any one of claims 1 to 4, wherein the antibody or fragment thereof comprises: VH CDR1 according to SEQ ID NO. 24, VH CDR2 according to SEQ ID NO. 25, VH CDR3 according to SEQ ID NO. 26, VL CDR1 according to SEQ ID NO. 12, VL CDR2 according to SEQ ID NO. 13, and VL CDR3 according to SEQ ID NO. 14.
  8. 8. The antibody or fragment thereof of any one of claims 1 to 4, wherein the antibody or fragment thereof comprises: VH CDR1 according to SEQ ID NO. 27, VH CDR2 according to SEQ ID NO. 28, VH CDR3 according to SEQ ID NO. 29, VL CDR1 according to SEQ ID NO. 15, VL CDR2 according to SEQ ID NO. 16, and VL CDR3 according to SEQ ID NO. 17.
  9. 9. The antibody or fragment thereof of any one of claims 1 to 4, wherein the antibody or fragment thereof comprises: VH CDR1 according to SEQ ID NO. 30, VH CDR2 according to SEQ ID NO. 31, VH CDR3 according to SEQ ID NO. 32, VL CDR1 according to SEQ ID NO. 18, VL CDR2 according to SEQ ID NO. 19, and VL CDR3 according to SEQ ID NO. 20.
  10. 10. The antibody or fragment thereof of claims 1 to 4, wherein the antibody or fragment thereof is selected from the group consisting of: (i) VH comprising the amino acid sequence of any one of SEQ ID NOs 5 to 8, and (Ii) VL comprising the amino acid sequence of any one of SEQ ID NOS.1-4.
  11. 11. The antibody or fragment thereof of any one of claims 1 to 4, wherein the antibody or fragment thereof comprises: (i) VH comprising the amino acid sequence of SEQ ID NO. 5, and (Ii) VL comprising the amino acid sequence of SEQ ID NO. 1.
  12. 12. The antibody or fragment thereof of any one of claims 1 to 4, wherein the antibody or fragment thereof comprises: (i) VH comprising the amino acid sequence of SEQ ID NO. 6, and (Ii) VL comprising the amino acid sequence of SEQ ID NO. 2.
  13. 13. The antibody or fragment thereof of any one of claims 1 to 4, wherein the antibody or fragment thereof comprises: (i) VH comprising the amino acid sequence of SEQ ID NO. 7, and (Ii) VL comprising the amino acid sequence of SEQ ID NO. 3.
  14. 14. The antibody or fragment thereof of any one of claims 1 to 4, wherein the antibody or fragment thereof comprises: (i) VH comprising the amino acid sequence of SEQ ID NO 8, and (Ii) VL comprising the amino acid sequence of SEQ ID NO. 4.
  15. 15. The antibody or fragment thereof of any one of claims 1 to 13, wherein the antibody or fragment thereof is a monoclonal antibody, fab, F (ab ') 2 , fab', scFv, or single domain antibody (sdAb).
  16. 16. The antibody or fragment thereof of any one of claims 1 to 15, wherein the antibody or fragment thereof comprises an IgG1 or IgG4 domain.
  17. 17. The antibody or fragment thereof of any one of claims 1 to 16, wherein the antibody or fragment thereof has an equilibrium dissociation constant (K D ) for CoV S glycoprotein or variant thereof of 50 nM or less, 10 nM or less, 1 nM or less, 0.5 nM or less, 0.1 nM or less, 0.05 nM or less, 0.01 nM or less, or 0.001 nM or less.
  18. 18. The antibody or fragment thereof of any one of claims 1 to 16, wherein the antibody or fragment thereof binds to CoV S glycoprotein or variant thereof with an equilibrium dissociation constant (Kd) of less than 1.0 x 10 -9 moles/liter (M), less than 1.0 x 10 -10 M, less than 1.0 x 10 -11 M, or less than 1.0 x 10 -12 M.
  19. 19. The antibody or fragment thereof of any one of claims 1 to 18, wherein the antibody or fragment thereof binds to one or more CoV S polypeptides having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a polypeptide according to any one of SEQ ID nos. 65-72.
  20. 20. The antibody or fragment thereof of any one of claims 1 to 19, wherein the antibody or fragment thereof binds to about 2 to about 20 CoV S glycoproteins.

Description

Anti-SARS-CoV-2 spike (S) antibodies and their use in treatment COVID-19 Cross Reference to Related Applications The present application claims priority from U.S. provisional application No. 63/586,184, filed on 28, 9, 2023. The above application is incorporated by reference in its entirety. Reference electronic sequence Listing This application contains a sequence table that has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The XML copy was created at 2024, 9/27, named 1450_106WO1_sequence_listing_09_27_2024 and is 105,759 bytes in size. Technical Field The present disclosure relates generally to anti-sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) antibodies and fragments thereof that are useful in the treatment of viral infections. In particular, anti-SARS-CoV-2 spike (S) antibodies and fragments thereof are useful in the treatment of coronavirus 19 disease (COVID-19). Background Infectious diseases remain a problem worldwide. Outbreaks of sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made more than 6.4 million people worldwide infected. Global deaths have exceeded 660 tens of thousands. The SARS-CoV-2 coronavirus belongs to the same viral family as the Severe acute respiratory syndrome coronavirus (SARS-CoV) and the middle east respiratory syndrome coronavirus (MERS-CoV), both of which have led to the death of hundreds of people in the past 17 years. SARS-CoV-2 causes disease COVID-19. Mutations in the SARS-CoV-2S spike protein enable the SARS-CoV-2 variant to escape neutralizing monoclonal antibodies produced by prior SARS-CoV-2 infection or by vaccination. Thus, it is desirable to develop broad-spectrum neutralizing antibodies for treatment COVID-19. Disclosure of Invention Provided herein are antibodies or fragments thereof that bind to SARS-CoV-2S glycoprotein of SARS-CoV-2 virus or variants thereof. The antibodies of the present disclosure are interchangeably referred to as anti-SARS-CoV-2S glycoprotein antibody and anti-CoV S glycoprotein antibody. in embodiments, provided herein are antibodies or fragments thereof that bind to the spike (S) glycoprotein of acute respiratory syndrome, sudden acute respiratory syndrome, coronavirus 2 (CoV), wherein the antibodies or fragments thereof comprise (i) a variable light chain complementarity determining region 1 (VL CDR 1) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 9, 12, 15 and 18, (ii) at least 80%, at least 85%, at least, At least 90%, at least 95% or 100% identical variable light chain complementarity determining region 2 (VL CDR 2), (iii) a variable light chain complementarity determining region 3 (VL CDR 3) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 11, 14, 17 and 20, (iv) a variable heavy chain complementarity determining region 1 (VH CDR 1) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOS: 21, 24, 27 and 30, (v) a variable heavy chain complementarity determining region selected from the group consisting of SEQ ID NOS: 22, 25. 28 and 31, and (vi) a variable heavy chain complementarity determining region 2 (VH CDR 2) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 23, 26, 29 and 32, and a variable heavy chain complementarity determining region 3 (VH CDR 3) having at least 80%, at least 85%, at least 90%, at least 95% or 100% identity to a sequence selected from the group consisting of SEQ ID NOs 23, 26, 29 and 32. In embodiments, provided herein are antibodies or fragments thereof that bind to the spike (S) protein of the sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2), wherein the antibodies or fragments thereof comprise (i) a polypeptide comprising at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least one polypeptide having a sequence as compared to SEQ ID NO 5-8 a variable heavy chain (VH) domain comprising an amino acid sequence having at least 98%, at least 99% or 100% identity to a polypeptide of any of SEQ ID NOs 1-4, and (ii) a variable light chain (VL) domain comprising an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a polypeptide of any of SEQ ID NOs 1-4. Drawing