Recombinant antibodies that recognize the C-terminal domains of Ebola virus nucleoprotein

• US 10,640,549 B2
• Filed: 10/16/2015
• Issued: 05/05/2020
• Est. Priority Date: 10/17/2014
• Status: Active Grant

• Current Assignee: University of Virginia Patent Foundation (University of Virginia)
• Original Assignee: University of Virginia Patent Foundation (University of Virginia)
• Inventors: Derewenda, Zygmunt S., Engel, Daniel A., Kossiakoff, Anthony, Davydova, Elena K., Jaskolowski, Mateusz
• Primary Examiner(s): Parkin, Jeffrey S
• Application Number:
  US15/518,417
• Publication Number:
  US 20180334494A1
• Time in Patent Office: 1,663 Days
• CPC Class Codes: A61K 39/42 viral
• CPC Class Codes: C07K 16/10 from RNA viruses
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C12N 2760/14111 Ebolavirus, e.g. Zaire ebolavirus
• CPC Class Codes: C12N 2760/14122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12Q 1/701 Specific hybridization probes
• CPC Class Codes: G01N 2333/08 RNA viruses
• CPC Class Codes: G01N 33/56983 Viruses

Abstract

This disclosure is directed to compositions and methods for utilizing the boundaries of the C-terminal domains of Nucleoprotein from Zaire Ebola virus as highly stable recombinant protein antigens to generate antibodies for diagnosis and treatment of Ebola virus infection.

Claims

1. An antibody that specifically binds to the C-terminal domain of the Nucleoprotein of Ebola virus, wherein the heavy chain of said antibody comprises the following complementarity determining region (CDR) sequences:

SEQ ID NO;

43, SEQ ID NO;

96, and SEQ ID NO;

145; and

the light chain of said antibody comprises the amino acid sequence of SEQ ID NO;

213.

2. The antibody of claim 1, wherein the antibody is a monoclonal antibody.

3. The antibody of claim 1, wherein the antibody is a chimeric antibody.

4. The antibody of claim 1, wherein the antibody is a fragment binding protein (Fab).

5. The antibody of claim 1, wherein the antibody is expressed as a recombinant antibody having a variant Fc domain.

7. The antibody of claim 1, wherein said antibody binds an amino acid sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4, and SEQ ID NO;

5.

8. The antibody of claim 1, wherein the antibody comprises a heavy chain of SEQ ID NO:

212 and a light chain of SEQ ID NO;

213.

11. A pharmaceutical composition comprising the antibody of claim 1, and a pharmaceutically acceptable carrier, excipient, or diluent.

12. The antibody of claim 1, wherein the antibody is labeled with a detectable moiety.

6. An antibody that specifically binds to the C-terminal domain of the Nucleoprotein of an Ebola virus strain selected from the group consisting of Tai Forest, Sudan, Bundibugyo, Reston, and Zaire, said antibody comprising

a heavy chain amino acid sequence that comprises the complementarity determining region (CDR) sequences of SEQ ID NO:

145, SEQ ID NO;

43, and SEQ ID NO;

96 and

a light chain amino acid sequence of SEQ ID NO;

213.

9. An antibody that specifically binds to the C-terminal domain of the Nucleoprotein of an Ebola virus strain, wherein the antibody is a Fab fragment consisting of a heavy chain sequence of SEQ ID NO:

212 and a light chain of SEQ ID NO;

213.

10. The antibody of claim 9, wherein the antibody is labeled with a detectable moiety.