Antimicrobial compositions comprising single domain antibodies and pseudomonas exotoxin

Patent metadata

Field	Value
Publication number	US-10010625-B2
Application number	US-201515108380-A
Country	US
Kind code	B2
Filing date	Jan 2, 2015
Priority date	Jan 2, 2014
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

Abstract

The present invention provides heavy chain immunoglobulins of the VHH type or fragment thereof having affinity for a target antigen of interest, including glycoprotein D2 (gD2) of HSV-2 or antigen thereof, and for envelope proteins of HIV-1 or an antigen thereof linked to Pseudomonas exotoxin A or functional fragments thereof. Also included are multimeric forms of the immunoglobulins and their use in the prevention and/or treatment of HSV2 and/or HIV-1.

First claim

The invention claimed is:

1. A heavy chain immunoglobulin of the VHH type or fragment thereof comprising an amino acid sequence of at least 85% identity to SEQ ID NO: 7, and having affinity for envelope proteins of HIV-1.

2. A heavy chain immunoglobulin of the VHH type or fragment thereof comprising an amino acid sequence of at least 85% identity to SEQ ID NO: 8, and having affinity for envelope proteins of HIV-1, which is covalently linked to the P. aeruginosa Exotoxin A subunit.

3. The heavy chain immunoglobulin of the VHH type or fragment thereof of claim 2 , having an amino acid sequence of at least 90% identity to SEQ ID NO: 8.

4. A multimeric molecule comprising a heavy chain immunoglobulin fragment of the VHH type according to claim 2 , in which VHH sequences are fused to yield multimeric units of 2 or more VHH units optionally linked via a spacer molecule.

5. A multimeric molecule comprising two or more VHH sequences according to claim 2 , which are fused to yield 2, 3, 4 or 5 or more VHH units optionally linked via a spacer molecule.

6. A nucleic acid encoding a heavy chain immunoglobulin fragment of the VHH type according to claim 1 .

7. An expression vector comprising the nucleic acid encoding a heavy chain immunoglobulin fragment of the VHH type according to claim 1 .

8. The expression vector of claim 6 comprising the nucleic acid sequence of SEQ ID NO: 6.

9. A micro-organism transformed with the expression vector of claim 8 .

10. A micro-organism according to claim 9 , wherein the micro-organism is Lactobacillus.

11. The micro-organism according to claim 10 , selected from the group consisting of L. jensenii, L. reuteri, L. gasseri, L. crispatus , and L. iners.

12. A method for treatment of an HIV-1 infection in a subject, comprising administering to the subject a heavy chain immunoglobulin or fragment thereof of claim 1 .

13. A method for treatment of an HIV-1 infection in a subject, comprising administering to subject a micro-organism of claim 9 expressing the heavy chain immunoglobulin or fragment of claim 1 .

14. A heavy chain immunoglobulin of the VHH type or fragment thereof comprising an amino acid sequence of at least 85% identity to SEQ ID NO: 11, and having affinity for envelope proteins of HIV-1.

15. A heavy chain immunoglobulin of the VHH type or fragment thereof comprising an amino acid sequence of at least 85% identity to SEQ ID NO: 12, and having affinity for envelope proteins of HIV-1, which is covalently linked to the P. aeruginosa Exotoxin A subunit.

16. The heavy chain immunoglobulin of the VHH type or fragment thereof of claim 15 , having an amino acid sequence of at least 90% identity to SEQ ID NO: 12.

17. A method for treatment of an HIV-1 infection in a subject, comprising administering to the subject the multimeric molecule of claim 4 .

18. A method for treatment of an HIV-1 infection in a subject, comprising administering to subject a micro-organism of claim 11 expressing the multimeric molecule of claim 5 .

Assignees

• Univ Johns Hopkins

Inventors

• Markham Richard
• Geoghegan Eileen

Classifications

• C07K16/087

  Herpes simplex virus · CPC title

• C07K2317/569

  Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® · CPC title

• C07K14/21 Primary

  from Pseudomonadaceae (F) · CPC title

• A61K47/48523 Primary

  Human Necessities · mapped topic

• A61K47/48484

  Human Necessities · mapped topic