# US 11,897,942 B2 · Eradication of bacterial biofilm using anti-amyloid monoclonal antibodies

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- Number: US 11,897,942 B2
- Document ID: US11897942B2
- Status: Granted
- Kind: B2
- Application number: 17/058,575
- Filed: 2019-05-24
- Published: 2021-04-29
- Granted: 2024-02-13
- Earliest claimed: 2018-05-25
- Assignees: Temple University of the Commonwealth System of Higher Education; Lankenau Institute of Medical Research
- Applicants: Temple University—Of The Commonwealth System of Higher Education; Lankenau Institute of Medical Research
- Inventors: Cagla Tukel Wilson; Scott Dessain
- Web page: https://patentgrep.com/patent/US11897942B2

## CPC

- C07K 16/1235: Salmonella (G)
- A23K 20/147: Polymeric derivatives, e.g. peptides or proteins
- A61K 39/39575: {against materials from other living beings excluding bacteria and viruses, e.g. protozoa, fungi, plants}
- A61P 31/04: Antibacterial agents
- C07K 14/245: Escherichia (G)
- C07K 14/255: Salmonella (G)
- C07K 16/1228: Enterobacterales (O), e.g. Citrobacter (G), Serratia (G), Proteus (G), Providencia (G), Morganella (G) or Yersinia (G)
- C07K 16/1232: Escherichia (G)
- C07K 16/18: against material from animals or humans
- A61K 2039/505: {comprising antibodies}
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A23K: FODDER
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 3)

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.

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

The composition of claim 1, further comprising an antibiotic.

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 1)

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.

### Claim 12 (depends on 1)

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

### Claim 13 (depends on 1)

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.

### Claim 14 (depends on 11)

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

### Claim 15 (depends on 1)

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.

### Claim 16 (depends on 15)

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

### Claim 17 (depends on 16)

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

### Claim 18 (depends on 17)

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

### Claim 19 (depends on 15)

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

### Claim 20 (depends on 19)

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