Neutralizing antibodies to plasmodium falciparum circumsporozoite protein and their use

Patent metadata

Field	Value
Publication number	US-11760794-B2
Application number	US-202117243455-A
Country	US
Kind code	B2
Filing date	Apr 28, 2021
Priority date	Feb 10, 2017
Publication date	Sep 19, 2023
Grant date	Sep 19, 2023

Abstract

Antibodies and antigen binding fragments that specifically bind to P. falciparum circumsporozoite protein and neutralize P. falciparum are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. The disclosed antibodies, antigen binding fragments, nucleic acids and vectors can be used, for example, to inhibit a P. falciparum infection.

First claim

It is claimed:

1. An isolated nucleic acid molecule encoding a monoclonal antibody or antigen binding fragment thereof, wherein the monoclonal antibody comprises:
a) a heavy chain variable region (V H ) comprising a heavy chain complementarity determining region (HCDR)1, a HCDR2, and a HCDR3 comprising the amino acid sequences set forth as SEQ ID NOs: 15, 45, 17, respectively, and
b) a light chain variable region (V L ) comprising a light chain complementarity determining region (LCDR)1, a LCDR2, and a LCDR3 comprising the amino acid sequences set forth as SEQ ID NOs: 18, 46, and 20, respectively.

2. The isolated nucleic acid molecule of claim 1 , wherein
a) the V H comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth as SEQ ID NO: 11 and b) the V L comprises an amino acid sequence at least 90% identical to the amino acid sequence set forth as SEQ ID NO: 12.

3. The isolated nucleic acid molecule of claim 1 , wherein the V H and/or the V L comprise human framework regions.

4. The isolated nucleic acid molecule of claim 1 , wherein the V H and the V L comprise the amino acid sequences set forth as SEQ ID NOs: 11 and 12, respectively.

5. The isolated nucleic acid molecule of claim 1 , wherein the monoclonal antibody comprises a human constant domain.

6. The isolated nucleic acid molecule of claim 1 , wherein the monoclonal antibody is a human antibody.

7. The isolated nucleic acid molecule of claim 1 , wherein the monoclonal antibody is an IgG.

8. The isolated nucleic acid molecule of claim 7 , wherein the V H and the V L comprise the amino acid sequences set forth as SEQ ID NOs: 13 and 14, respectively.

9. The isolated nucleic acid molecule of claim 1 , wherein the monoclonal antibody comprises a recombinant constant domain comprising a modification that increases the half-life of the antibody.

10. The isolated nucleic acid molecule of claim 9 , wherein the modification increases binding to the neonatal Fc receptor.

11. The isolated nucleic acid molecule of claim 10 , wherein the recombinant constant domain is an IgG 1 constant domain comprising M428L and N434S mutations.

12. The isolated nucleic acid molecule of claim 1 , encoding the antigen binding fragment, wherein the antigen binding fragment comprises the V H and the V L of the monoclonal antibody.

13. The isolated nucleic acid molecule of claim 12 , wherein the antigen binding fragment is a Fv, Fab, F(ab′) 2 , scFV or a scFV 2 fragment.

14. The isolated nucleic acid molecule of claim 13 , comprising the V H sequence set forth as SEQ ID NO: 57 and the V L nucleotide sequence set forth as SEQ ID NO: 58.

15. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises a cDNA encoding the antibody or antigen binding fragment.

16. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule is an RNA molecule encoding the antibody or antigen binding fragment.

17. The isolated nucleic acid molecule of claim 1 , further comprising a promoter.

18. An expression vector comprising the nucleic acid molecule of claim 1 .

19. A method of producing an antibody comprising
expressing the expression vector of claim 18 in a host cell; and
purifying the antibody.

20. A composition comprising an effective amount of the nucleic acid molecule of claim 1 , and a pharmaceutically acceptable carrier.

Assignees

• Us Health
• Sanaria Inc

Inventors

• Seder Robert
• Kisalu Neville
• Idris Azza
• Flynn Barbara
• Hoffman Stephen

Classifications

• C07K16/205 Primary

  Plasmodium · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/92

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