Eradication of bacterial biofilm using anti-amyloid monoclonal antibodies

Patent metadata

Field	Value
Publication number	US-11897942-B2
Application number	US-201917058575-A
Country	US
Kind code	B2
Filing date	May 24, 2019
Priority date	May 25, 2018
Publication date	Feb 13, 2024
Grant date	Feb 13, 2024

Abstract

The present invention features compositions comprising an anti-amyloid antibody and methods of treating microbial infection and treating or preventing microbial biofilms using the composition.

First claim

What is claimed is:

1. A composition comprising a therapeutic antibody, wherein the antibody is specific for binding to an epitope of curli and further wherein the epitope of curli comprises a sequence having homology to an antibody binding site of one or more heterologous amyloid proteins;
wherein the antibody is a monoclonal antibody selected from the group consisting of:
a) ALZ.3H3, comprising at least one heavy chain amino acid sequence as set forth in SEQ ID NO:2 and at least one light chain amino acid sequence as set forth in SEQ ID NO:35;
b) ALZ.4G1, comprising at least one heavy chain amino acid sequence as set forth in SEQ ID NO:61 and at least one light chain amino acid sequence as set forth in SEQ ID NO:63; and
c) ALZ.4A6, comprising at least one of a heavy chain amino acid sequence as set forth in SEQ ID NO:57 and at least one light chain amino acid sequence as set forth in SEQ ID NO:59.

2. The composition of claim 1 , wherein the antibody inhibits fibrillization of one or more heterologous amyloid proteins.

3. The composition of claim 1 , wherein the antibody prevents biofilm formation or alters biofilm architecture.

4. The composition of claim 1 , wherein the antibody is effective in reducing biofilm mass.

5. The composition of claim 3 , wherein the biofilm mass is associated with a bacteria selected from the group consisting of gram-positive, gram-negative, and a combination thereof.

6. The composition of claim 1 , wherein the antibody inhibits amyloid-β fibrillization and prevents biofilm formation or alters biofilm architecture.

7. The composition of claim 1 , wherein the antibody is a monoclonal antibody selected from the group consisting of:
a) ALZ.3H3, comprising at least one heavy chain amino acid sequence as set forth in SEQ ID NO:2 and at least one light chain amino acid sequence as set forth in SEQ ID NO:35; and
b) ALZ.4G1, comprising at least one heavy chain amino acid sequence as set forth in SEQ ID NO:61 and at least one light chain amino acid sequence as set forth in SEQ ID NO:63.

8. The composition of claim 1 , wherein the composition is for application to a surface of a medical device.

9. The composition of claim 1 , further comprising an antibiotic.

10. The composition of claim 1 , further comprising one or more pharmaceutically acceptable carriers or excipients.

11. The composition of claim 1 , wherein the formulation is a topical formulation in the form of a cream, a lotion, an ointment, a hydrogel, a colloid, a gel, a foam, an oil, a milk, a suspension, a wipe, a sponge, a solution, an emulsion, a paste, a patch, a pledget, a swab, a dressing, a spray or a pad.

12. A method of decolonizing a microbial organism comprising contacting the microbial organism with a composition according to claim 1 .

13. A method of destroying or disrupting or inhibiting or reducing biofilm formation of a microbial organism comprising contacting the microbial organism with a composition according to claim 1 .

14. The method of claim 11 , wherein the microbial organism is a bacterium.

15. A method of treating a microbial infection in a subject comprising administering to the subject a therapeutically effective amount of the composition of claim 1 .

16. The method of claim 15 , wherein the microbial infection is a bacterial infection.

17. The method of claim 16 , wherein the bacterial infection is characterized by colonization of a bacterium.

18. The method of claim 17 , wherein the bacterial infection is characterized by biofilm formation.

19. The method of claim 15 , wherein the microbial infection is a topical infection.

20. The method of claim 19 , wherein the topical infection is selected from wound, ulcer and lesion.

Assignees

• Temple University—Of the Commonwealth System of Higher Education
• Lankenau Institute Of Medical Res

Inventors

• Wilson Cagla Tukel
• Dessain Scott

Classifications

• C07K16/1235 Primary

  Salmonella (G) · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• C07K16/1228 Primary

  Enterobacterales (O), e.g. Citrobacter (G), Serratia (G), Proteus (G), Providencia (G), Morganella (G) or Yersinia (G) · CPC title

• C07K16/1232

  Escherichia (G) · CPC title

• C07K14/195 Primary

  from bacteria · CPC title