Anti-malarial compositions

Patent metadata

Field	Value
Publication number	US-10501534-B2
Application number	US-201816133143-A
Country	US
Kind code	B2
Filing date	Sep 17, 2018
Priority date	Dec 5, 2013
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

Abstract

This disclosure provides antibodies that are useful for preventing and/or treating malaria. The epitope to which the antibodies bind is in close proximity to the conserved proteolytic cleavage site of P. falciparum circumsporozoite protein (CSP), and the antibodies provided in this disclosure can prevent cleavage and inhibit P. falciparum sporozoites from invading the liver.

First claim

The invention claimed is:

1. A method of producing a heavy chain of an antibody, comprising growing a host cell comprising a gene expression construct encoding the heavy chain under conditions which permit expression of the gene expression construct, wherein the gene expression construct comprises a coding sequence for the heavy chain, wherein the variable region of the heavy chain comprises:
(i) a first heavy chain complementarity determining region (CDR H ) comprising the amino acid sequence SEQ ID NO:1; a second CDR H comprising the amino acid sequence SEQ ID NO:2; and a third CDR H comprising the amino acid sequence SEQ ID NO:3; or
(ii) the complementarity determining regions of the heavy chain variable region of the antibody deposited under Accession No. MRA-1242.

2. The method of claim 1 , wherein the variable region of the heavy chain comprises the first CDR H comprising the amino acid sequence SEQ ID NO:1; the second CDR H comprising the amino acid sequence SEQ ID NO:2; and the third CDR H comprising the amino acid sequence SEQ ID NO:3.

3. The method of claim 1 , wherein the variable region of the heavy chain comprises the CDRs of the heavy chain of the antibody deposited under Accession No. MRA-1242.

4. A method of producing a light chain of an antibody, comprising growing a host cell comprising a gene expression construct encoding the light chain under conditions which permit expression of the gene expression construct, wherein the gene expression construct comprises a coding sequence for the light chain, wherein the variable region of the light chain comprises:
(i) a first CDR L comprising the amino acid sequence SEQ ID NO:4; a second CDR L comprising the amino acid sequence SEQ ID NO:5; and a third CDR L comprising the amino acid sequence SEQ ID NO:6; or
(ii) the CDRs of the light chain variable region of the antibody deposited under Accession No. MRA-1242.

5. The method of claim 4 , wherein the light chain variable region comprises the first CDR L comprising the amino acid sequence SEQ ID NO:4; the second CDR L comprising the amino acid sequence SEQ ID NO:5; and the third CDR L comprising the amino acid sequence SEQ ID NO:6.

6. The method of claim 4 , wherein the light chain variable region comprises the CDRs of the light chain of the antibody deposited under Accession No. MRA-1242.

7. The method of claim 1 , wherein the host cell further comprises a second gene expression construct comprising a coding sequence for a light chain of the antibody, wherein the light chain variable region comprises:
(i) a first CDR L comprising the amino acid sequence SEQ ID NO:4; a second CDR L comprising the amino acid sequence SEQ ID NO:5; and a third CDR L comprising the amino acid sequence SEQ ID NO:6; or
(ii) the CDRs of the light chain variable region of the antibody deposited under Accession No. MRA-1242,

wherein the conditions under which the host cell is grown permit expression of the second gene expression construct.

8. The method of claim 7 , wherein the variable region of the heavy chain comprises the CDRs of the heavy chain of the antibody deposited under Accession No. MRA-1242 and wherein the variable region of the light chain comprises the CDRs of the light chain of the antibody deposited under Accession No. MRA-1242.

9. The method of claim 1 , wherein the method further comprises producing a light chain of the antibody, wherein the gene expression construct further comprises a coding sequence for the light chain of the antibody, wherein the light chain variable region comprises:
(i) a first CDR L comprising the amino acid sequence SEQ ID NO:4; a second CDR L comprising the amino acid sequence SEQ ID NO:5; and a third CDR L comprising the amino acid sequence SEQ ID NO:6; or
(ii) the CDRs of the light chain variable region of the antibody deposited under Accession No. MRA-1242.

10. The method of claim 9 , wherein the variable region of the heavy chain comprises the CDRs of the heavy chain of the antibody deposited under Accession No. MRA-1242 and wherein the variable region of the light chain comprises the CDRs of the light chain of the antibody deposited under Accession No. MRA-1242.

11. The method of claim 1 , wherein framework regions of the heavy chain are humanized.

12. The method of claim 1 , wherein framework regions of the heavy chain are human framework regions.

13. The method of claim 4 , wherein framework regions of the light chain are humanized.

14. The method of claim 4 , wherein framework regions of the light chain are human framework regions.

Assignees

• Leidos Inc
• Us Health
• The U S Of America As Represented By The Secretary Dept Of Health And Human Services

Inventors

• Gutierrez Gabriel M
• Pannucci James
• Noe Amy
• Huang Steve Chienwen
• Winram Scott
• Mo Annie Xiaoyan

Classifications

• A61P33/06

  Antimalarials · CPC title

• C07K16/205 Primary

  Plasmodium · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K39/015

  Hemosporidia antigens, e.g. Plasmodium antigens · 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