Anti-plasmodium parasite antibodies

Patent metadata

Field	Value
Publication number	US-9611318-B2
Application number	US-201314418677-A
Country	US
Kind code	B2
Filing date	Jul 31, 2013
Priority date	Aug 3, 2012
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

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 merozoite surface protein 10 (MSP10). 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

The invention claimed is:

1. An isolated monoclonal human antibody, or antigen-binding portion thereof, that binds specific to the first epidermal growth factor-like domain of MSP-10 (SEQ ID NO: 13) of Plasmodium falciparum , wherein said antibody or antigen-binding portion thereof inhibits the invasion of a Plasmodium falciparum parasite into the erythrocyte and/or the growth of the Plasmodium falciparum parasite within the erythrocyte by at least 50%, wherein the antibody or the antigen-binding portion thereof has a light chain variable region (LCVR) and a heavy chain variable region (HCVR), and wherein the LCVR comprises the CDR sequences of SEQ ID NOs 1, 2 and 3 and the HCVR comprises the CDR sequences of SEQ ID NOs 4, 5 and 6.

2. An isolated monoclonal human antibody, or antigen-binding portion thereof, that binds specific to the first epidermal growth factor-like domain of MSP-10 (SEQ ID NO: 13) of Plasmodium falciparum , wherein said antibody or antigen-binding portion thereof inhibits the invasion of a Plasmodium falciparum parasite into the erythrocyte and/or the growth of the Plasmodium falciparum parasite within the erythrocyte by at least 50%, wherein the antibody or the antigen-binding portion thereof has a light chain variable region (LCVR) and a heavy chain variable region (HCVR), and wherein the LCVR comprises the CDR sequences of SEQ ID NOs 16, 17 and 18 and the HCVR comprises the CDR sequences of SEQ ID NOs 4, 5 and 6.

3. The isolated monoclonal human antibody according to claim 1 , wherein the LCVR further comprises the polypeptide of SEQ ID NO: 15 and the HCVR further comprises the polypeptide of SEQ ID NO: 14.

4. The isolated monoclonal human antibody according claim 1 , wherein the LCVR further comprises the polypeptide of SEQ ID NO: 19 and the HCVR further comprises the polypeptide of SEQ ID NO: 14.

5. The isolated monoclonal human antibody according to claim 1 , wherein the antigen-binding portion is a Fab fragment, a F(ab')2 fragment, a single chain Fv fragment, or multimers thereof.

6. The isolated monoclonal human antibody according to claim 1 , comprising a heavy chain constant region selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE constant regions.

7. The isolated antibody or antigen-binding portion thereof according to claim 1 for use in the treatment of malaria, in particular of malaria tropica.

8. The isolated monoclonal human antibody according to claim 2 , wherein the LCVR further comprises the polypeptide of SEQ ID NO: 15 and the further comprises the polypeptide of SEQ ID NO: 14.

9. The isolated monoclonal human antibody according claim 2 , wherein the LCVR further comprises the polypeptide of SEQ ID NO: 19 and the HCVR further comprises the polypeptide of SEQ ID NO: 14.

10. The isolated monoclonal human antibody according to claim 2 , wherein the antigen-binding portion is a Fab fragment, a F(ab')2 fragment, a single chain Fv fragment, or multimers thereof.

11. The isolated monoclonal human antibody according to claim 2 , comprising a heavy chain constant region selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE constant regions.

12. The isolated antibody or antigen-binding portion thereof according to claim 2 for use in the treatment of malaria, in particular of malaria tropica.

Assignees

• Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E V
• Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E V

Inventors

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

Classifications

• C07K16/205 Primary

  Plasmodium · CPC title

• C07K2317/92

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

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title