Arena virus monoclonal antibodies and uses

Patent metadata

Field	Value
Publication number	US-12358971-B2
Application number	US-202318392147-A
Country	US
Kind code	B2
Filing date	Dec 21, 2023
Priority date	Dec 5, 2016
Publication date	Jul 15, 2025
Grant date	Jul 15, 2025

Abstract

Disclosed herein are compositions comprising recombinant arenavirus monoclonal antibodies and antigen-binding fragments thereof, as well as therapeutic methods using the antibodies. In some embodiments, the antibodies provide pan-arenavirus protection against a number of arenavirus types and strains.

First claim

What is claimed is:

1. An antigen-binding composition comprising a combination of three recombinant monoclonal neutralizing antibodies or neutralizing antigen-binding antibody fragments thereof, which are specific to Lassa virus glycoprotein, wherein the composition comprises:
a recombinant human monoclonal antibody or an antigen-binding antibody fragment thereof comprising a V H CDR1 of SEQ ID NO: 83, a V H CDR2 of SEQ ID NO: 84, a V H CDR3 of SEQ ID NO: 85, a V L CDR1 of SEQ ID NO: 125, a V L CDR2 of sequence Gly Ala Ser, and a V L CDR3 of SEQ ID NO: 126;
a recombinant human monoclonal antibody or an antigen-binding antibody fragment thereof comprising a V H CDR1 of SEQ ID NO: 92, a V H CDR2 of SEQ ID NO: 93, a V H CDR3 of SEQ ID NO: 94, a V L CDR1 of SEQ ID NO: 131, a V L CDR2 of sequence Glu Val Ser, and a V L CDR3 of SEQ ID NO: 132; and
a recombinant human monoclonal antibody or an antigen-binding antibody fragment thereof comprising a V H CDR1 of SEQ ID NO: 98, a V H CDR2 of SEQ ID NO: 99, a V H CDR3 of SEQ ID NO: 100, a V L CDR1 of SEQ ID NO: 135, a V L CDR2 of sequence Gly Ala Ser, and a V L CDR3 of SEQ ID NO: 136.

2. The composition of claim 1 , wherein each antigen-binding antibody fragment is selected from the group consisting of a Fab, a Fab′, and a F(ab′) 2 fragment.

3. A pharmaceutical composition for treating a Lassa virus or a lymphocytic choriomeningitis virus infection comprising the composition of claim 1 and a pharmaceutically acceptable carrier.

4. The composition of claim 1 wherein the composition comprises:
a recombinant human monoclonal antibody or an antigen-binding antibody fragment thereof comprising a V H of SEQ ID NO: 39 and a V L of SEQ ID NO: 55;
a recombinant human monoclonal antibody or an antigen-binding antibody fragment thereof comprising a V H of SEQ ID NO: 42 and a V L of SEQ ID NO: 58; and
a recombinant human monoclonal antibody or an antigen-binding antibody fragment thereof comprising a V H of SEQ ID NO: 44 and a V L of SEQ ID NO: 60.

5. The composition of claim 4 , wherein each antigen-binding antibody fragment is selected from the group consisting of a Fab, a Fab′, and a F(ab′) 2 fragment.

6. A pharmaceutical composition for treating infection by a Lassa virus or a lymphocytic choriomeningitis virus comprising the composition of claim 4 and a pharmaceutically acceptable carrier.

7. An antigen-binding composition comprising a recombinant human monoclonal neutralizing antibody or a neutralizing antigen-binding antibody fragment thereof, which is specific for Lassa virus glycoprotein; the antibody or antibody fragment thereof comprising a V H CDR1 of SEQ ID NO: 83, a V H CDR2 of SEQ ID NO: 84, a V H CDR3 of SEQ ID NO: 85, a V L CDR1 of SEQ ID NO: 125, a V L CDR2 of sequence Gly Ala Ser, and a V L CDR3 of SEQ ID NO: 126.

8. The composition of claim 7 , wherein the antigen-binding antibody fragment is selected from the group consisting of a Fab, a Fab′, and a F(ab′) 2 fragment.

9. The composition of claim 7 wherein the composition comprises a recombinant human monoclonal antibody or an antigen-binding antibody fragment thereof comprising a V H of SEQ ID NO: 39 and a V L of SEQ ID NO: 55.

10. A pharmaceutical composition for treating infection by a Lassa virus or a lymphocytic choriomeningitis virus comprising the composition of claim 7 and a pharmaceutically acceptable carrier.

11. An antigen-binding composition comprising a recombinant human monoclonal neutralizing antibody or a neutralizing antigen-binding antibody fragment thereof, which is specific for Lassa virus glycoprotein; the antibody or antibody fragment thereof comprising a V H CDR1 of SEQ ID NO: 92, a V H CDR2 of SEQ ID NO: 93, a V H CDR3 of SEQ ID NO: 94, a V L CDR1 of SEQ ID NO: 131, a V L CDR2 of sequence Glu Val Ser, and a V L CDR3 of SEQ ID NO: 132.

12. The composition of claim 11 , wherein the antigen-binding antibody fragment is selected from the group consisting of a Fab, a Fab′, and a F(ab′) 2 fragment.

13. The composition of claim 11 , wherein the composition comprises a recombinant human monoclonal antibody or an antigen-binding antibody fragment thereof comprising a V H of SEQ ID NO: 42 and a V L of SEQ ID NO: 58.

14. A pharmaceutical composition for treating infection by a Lassa virus or a lymphocytic choriomeningitis virus comprising the composition of claim 11 and a pharmaceutically acceptable carrier.

15. A method of treating or preventing a Lassa virus infection or a lymphocytic choriomeningitis virus infection in a subject comprising administering the composition of claim 1 to the subject.

16. A method of treating or preventing a Lassa virus infection or a lymphocytic choriomeningitis virus infection in a subject comprising administering the composition of claim 4 to the subject.

17. A method of treating or preventing a Lassa virus infection or a lymphocytic choriomeningitis virus infection in a subject comprising administering the composition of claim 7 to the subject.

18. A method of treating or preventing a Lassa virus infection or a lymphocytic choriomeningitis virus infection in a subject comprising administering the composition of claim 9 to the subject.

19. A method of treating or preventing a Lassa virus infection in a subject comprising administering the composition of claim 11 to the subject.

20. A method of treating or preventing a Lassa virus infection in a subject comprising administering the composition of claim 13 to the subject.

Assignees

• The Administrators Of The Tulane Educational Fund
• Scripps Research Inst
• Univ Texas
• Zalgen Labs Llc
• The Boad Of Regents Of The Univ Of Texas System
• The Scripps Resesrch Inst

Inventors

• Branco Luis M
• Garry Robert F
• Robinson James E
• Saphire Erica O
• Hastie Kathryn M
• Geisbert Thomas W

Classifications

• C12N2760/10011

  Arenaviridae · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title