Anti-parasitic complexes

Patent metadata

Field	Value
Publication number	US-10344082-B2
Application number	US-201515507173-A
Country	US
Kind code	B2
Filing date	Aug 21, 2015
Priority date	Aug 26, 2014
Publication date	Jul 9, 2019
Grant date	Jul 9, 2019

Abstract

The technology provided herein relates to novel anti-parasitic complexes, in particular recombinant fusion proteins suitable as human and/or animal drugs against a parasite of the phylum Apicomplexa, in particular against Plasmodium falciparum ( P. falciparum ) comprising at least one component A and at least one component B, characterized in that component A has a binding activity for cellular surface structures presented on the surface of a parasite of the phylum Apicomplexa or for parasitic antigens presented on a parasitized host cell, and component B is a compound having anti-parasitic activity.

First claim

What is claimed is:

1. A complex comprising at least one component A and at least one component B, characterized in that component A is an antibody or antibody fragment that has a binding activity for cellular surface structures presented on the surface of a parasite of the genus Plasmodium and component B is a variant of human granzyme B having direct anti-parasitic activity, wherein the cellular surface structure is selected from the group consisting of cell traversal protein for ookinetes and sporozoites (CelTos), circumsporozoite protein (CSP), Exported Protein 1 (EXPO, Merozoite surface protein 1 (MSP1), Merozoite surface protein 2 (MSP2), Merozoite surface protein 3 (MSP3), Merozoite surface protein 4 (MSP4), Merozoite surface protein 5 (MSPS), Merozoite surface protein 7 (MSP7), Merozoite surface protein 8 (MSPS), Merozoite surface protein 9 (MSPS), Merozoite surface protein 10 (MSP10), Merozoite-specific thrombospondin-related anonymous protein (mTRAP), Plasmodium falciparum 6-cys protein (Pf38), Reticulocyte binding protein homologue 1 (Rh1), Reticulocyte binding protein 2 homolog a (Rh2a), Reticulocyte binding protein 2 homologue b (Rh2b), Reticulocyte binding protein homologue 4 (Rh4), Reticulocyte binding protein homologue 5 (Rh5), Rh5 interacting protein (Ripr), rhoptry neck protein 2 (RON2), rhoptry neck protein 4 (RON4), rhoptry neck protein 5 (RON5), Plasmodium falciparum rhoptry neck protein 6 (PfRON6), Thrombospondin-related apical membrane protein (TRAMP), Apical membrane antigen 1 (AMA1), Glutamine rich protein (GLURP), High Molecular Weight Rhoptry Protein-2 (RhopH2) and High Molecular Weight Rhoptry Protein-3 (RhopH3), and wherein the variant of human granzyme B comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO:9, and SEQ ID NO: 10.

2. The complex according to claim 1 , wherein the parasite of the genus Plasmodium is selected from the group consisting of P. falciparum, P. vivax, P. ovate, P. knowlesi , and P. malariae.

3. The complex according to claim 1 , wherein the parasitic cellular surface structures are presented in the pre-erythrocytic stage and/or the blood stage.

4. The complex according to claim 1 , wherein the antibody or antibody fragment is selected from the group consisting of an Fab, a scFv, a single domain, a bis scFv, an Fab 2 , an Fab 3 , a minibody, a diabody, a triabody, a tetrabody and a tandab.

5. The complex according to claim 4 , wherein the scFv is specific for an epidermal growth-factor-like domain of merozoite surface protein 4 (MSP4).

6. The complex according to claim 1 , wherein the complex is a fusion protein.

7. The complex according to claim 1 containing one or more supplementary components S in addition to said components A and B, wherein component S is selected from the group consisting of an inducible promoter capable of regulating expression, a leader sequence capable of controlling protein biosynthesis, a Histadine (HIS) tag, an affinity tag, and a translocation domain amphipathic sequence capable of translocating a fusion protein into a target cell.

8. A complex comprising the amino acid sequence of SEQ ID NO: 1.

9. The complex according to claim 4 , wherein component A is the single chain variable fragment (scFv).

10. A pharmaceutical composition comprising a complex according to claim 1 in combination with a pharmacologically acceptable carrier, diluent, stabilizer or formulation.

11. A nucleic acid molecule coding for the fusion protein according to claim 6 .

12. A vector carrying the nucleic acid molecule according to claim 11 .

13. A cell transfected with the vector according to claim 12 .

14. A method for preparing a complex, wherein the method comprises culturing the cell according to claim 13 and isolating the complex from the cell culture.

Assignees

• Fraunhofer Ges Forschung

Inventors

• Fendel Rolf
• Kapelski Stephanie
• Barth Stefan
• Fischer Rainer
• Reimann Andreas

Classifications

• A61K47/6835

  the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site · CPC title

• C12N9/6467

  Granzymes, e.g. granzyme A (3.4.21.78); granzyme B (3.4.21.79) · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C12Y304/21079

  Granzyme B (3.4.21.79) · CPC title

• A61K47/6815

  Enzymes · CPC title