Anti-plasmodium parasite antibodies

Patent metadata

Field	Value
Publication number	US-10577412-B2
Application number	US-201615566176-A
Country	US
Kind code	B2
Filing date	Apr 11, 2016
Priority date	Apr 12, 2015
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

The technology provided herein relates to novel human antibodies against Plasmodium parasites, in particular against the malaria parasite Plasmodium falciparum . The present disclosure pertains to antibodies against apical membrane antigen 1 (AMA-1). These antibodies have high affinity e.g. to Plasmodium falciparum schizonts and merozoites, inhibit the reinvasion of merozoites into erythrocytes and thereby neutralize parasitic multiplication.

First claim

What is claimed is:

1. An expression vector comprising a nucleic acid sequence encoding a human antibody or an antigen-binding portion thereof operably linked to a viral regulatory sequence, characterized in that the antibody or antigen-binding portion thereof binds to apical membrane antigen 1 (AMA-1) of a Plasmodium parasite, wherein the antibody or antigen-binding portion thereof inhibits invasion of a Plasmodium parasite into an erythrocyte and/or growth of the Plasmodium parasite within the erythrocyte, wherein the antigen-binding portion of the antibody has a light chain variable region (LCVR) comprising a CDR1 comprising SEQ ID NO:1, a CDR2 comprising SEQ ID NO:2, and a CDR3 comprising SEQ ID NO:3, and a heavy chain variable region (HCVR) comprising a CDR1 comprising SEQ ID NO:4, a CDR2 comprising SEQ ID NO:5, and a CDR3 comprising SEQ ID NO:6.

2. The expression vector according to claim 1 , wherein the nucleic acid sequence comprises SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, and/or SEQ ID NO:12.

3. A host cell comprising the expression vector according to claim 1 .

4. A method of producing a human antibody or antigen-binding portion thereof that binds to apical membrane antigen 1 (AMA-1) of a Plasmodium parasite, wherein the antibody or antigen-binding portion thereof inhibits invasion of a Plasmodium parasite into an erythrocyte and/or growth of the Plasmodium parasite within the erythrocyte, wherein the antigen-binding portion of the antibody has a light chain variable region (LCVR) comprising a CDR1 comprising SEQ ID NO:1, a CDR2 comprising SEQ ID NO:2, and a CDR3 comprising SEQ ID NO:3, and a heavy chain variable region (HCVR) comprising a CDR1 comprising SEQ ID NO:4, a CDR2 comprising SEQ ID NO:5, and a CDR3 comprising SEQ ID NO:6, characterized in that the method comprises:
(a) providing a nucleic acid construct comprising a nucleic acid encoding the antibody or antigen-binding portion thereof,
(b) introducing the nucleic acid construct into a host cell or adding the nucleic acid construct to a cell-free lysate obtained from eukaryotic or prokaryotic cells, and
(c) maintaining the host cell or the cell-free lysate under conditions permitting expression of the antibody or the antigen-binding portion thereof, and optionally
(d) isolating and/or purifying and/or processing of the antibody or antigen-binding portion thereof.

5. The method according to claim 4 , wherein the host cell is a plant cell, a eukaryotic cell line, or a microorganism.

6. The expression vector of claim 1 , wherein the LCVR/HCVR is at least 80% identical to the amino acid sequence of SEQ ID NO: 13 or SEQ ID NO: 14.

7. The expression vector of claim 1 , wherein the LCVR comprises SEQ ID NO: 13 and the HCVR comprises SEQ ID NO: 14.

8. The expression vector of claim 1 , wherein the antibody or antigen-binding portion thereof binds to AMA-1 of a plurality of different Plasmodium parasites, optionally to AMA-1 of a plurality of different Plasmodium falciparum parasites including the P. falciparum parasite strains 3D7, HB3, FCR3, and K1.

9. The expression vector of claim 1 , wherein the antibody or antigen-binding portion thereof is selected from the group consisting of a Fab fragment, a F(ab′) 2 fragment, a single chain Fv fragment, and a multimer thereof.

10. The method according to claim 5 , wherein the plant cell is Nicotiana benthamiana or Nicotiana tabacum.

11. The method according to claim 5 , wherein the eukaryotic cell line is a CHO cell line or a HEK 293 cell line.

12. The method according to claim 5 , wherein the microorganism is Pichia pastoris.

Assignees

• Fraunhofer Ges Forschung

Inventors

• Fendel Rolf
• Barth Stefan
• Fischer Rainer
• Reimann Andreas
• Maskus Dominika
• Klockenbring Torsten

Classifications

• A61P33/06

  Antimalarials · CPC title

• A61P33/00

  Antiparasitic agents · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title

• C07K16/205 Primary

  Plasmodium · CPC title