Antimicrobial compositions comprising single domain antibodies and pseudomonas exotoxin

Patent metadata

Field	Value
Publication number	US-10376596-B2
Application number	US-201816007052-A
Country	US
Kind code	B2
Filing date	Jun 13, 2018
Priority date	Jan 2, 2014
Publication date	Aug 13, 2019
Grant date	Aug 13, 2019

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, wherein the heavy chain immunoglobulin of the VHH type or fragment thereof comprises an amino acid sequence of at least 90% identity to SEQ ID NO: 3.

2. The heavy chain immunoglobulin of the VHH type or fragment thereof of claim 1 , wherein the immunoglobulin or fragment thereof 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 , comprising an amino acid sequence of at least 90% identity to SEQ ID NO: 4.

4. A multimeric molecule comprising a heavy chain immunoglobulin fragment of the VHH type according to claim 3 , 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 4 , 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 gene encoding the heavy chain immunoglobulin fragment according to claim 6 .

8. The expression vector of claim 7 comprising the nucleic acid sequence of SEQ ID NO: 6.

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

10. The micro-organism according to claim 9 , wherein the micro-organism is of the genus 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 HSV2 infection in as subject, comprising administering to the subject, an effective amount of the immunoglobulin of claim 1 .

Assignees

• Univ Johns Hopkins

Inventors

• Markham Richard
• Geoghegan Eileen

Classifications

• C07K2317/569

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

• C07K2319/55

  containing a fusion with a toxin, e.g. diphteria toxin · CPC title

• A61K47/6813

  the drug being a peptidic cytokine, e.g. an interleukin or interferon · CPC title

• A61K47/6839 Primary

  the antibody targeting material from viruses · CPC title

• C07K14/21 Primary

  from Pseudomonadaceae (F) · CPC title