COMPOSITIONS AND METHODS FOR THE REMOVAL OF BIOFILMS

• US 20160095316A1
• Filed: 10/16/2015
• Published: 04/07/2016
• Est. Priority Date: 09/09/2010
• Status: Active Grant

• Current Assignee: Nationwide Children's Hospital Incorporated, University of Southern California
• Original Assignee: Nationwide Children's Hospital Incorporated
• Inventors: Goodman, Steven D., Bakaletz, Lauren O.
• Granted Patent: US 10,595,530 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A01N 37/46 N-acyl derivatives
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods of breaking down a biofilm or inhibiting, preventing or treating a microbial infection that produces a biofilm are disclosed, which involves administration of a polypeptide that has one or more HMG-box domains to a subject suffering from the infection or having the biofilm. By competing with microbial proteins that bind to DNA scaffold in the biofilm, these polypeptides destabilize the biofilm leading to destruction and removal of the biofilm by the immune system.

Claims

1. A method for inhibiting, competing or titrating the binding of a deoxyribonucleic acid B II (DNABII) polypeptide to a microbial DNA in a biofilm, comprising contacting the microbial DNA in the biofilm with an effective amount of an isolated or recombinant polypeptide comprising a high mobility group-box domain (HMG-box domain) thereby inhibiting, competing or titrating the binding of the DNABII polypeptide to the microbial DNA.

2. The method of claim 1, wherein the contacting is in vitro or in vivo.

3. The method of claim 1, wherein the isolated or recombinant polypeptide comprising the HMG-box domain comprises one or more of:

(a) an isolated or recombinant polypeptide high mobility group box 1 (HMGB1) comprising from about amino acid 6 to about amino acid 76 or from about amino acid 90 to about amino acid 138 of SEQ ID NO;

1 or a polypeptide having at least 90% sequence identity to each thereof;

(b) an isolated or recombinant polypeptide high mobility group box 2 (HMGB2) comprising from about amino acid 9 to about amino acid 76 or from about amino acid 95 to about amino acid 160 of SEQ ID NO;

2 or a polypeptide having at least 90% sequence identity to each thereof;

(c) an isolated or recombinant polypeptide high mobility group box 3 (HMGB3) comprising from about amino acid 9 to about amino acid 75 or from about amino acid 98 to about amino acid 158 of SEQ ID NO;

3 or a polypeptide having at least 90% sequence identity to each thereof;

or

(d) an isolated or recombinant polypeptide high mobility group box 4 (HMGB

     4) comprising from about amino acid 9 to about amino acid 75 or from about amino acid 93 to about amino acid 158 of SEQ ID NO;

4 or a polypeptide having at least 90% sequence identity to each thereof.

4. The method of claim 3, wherein the isolated or recombinant polypeptide comprising an HMG-box (high mobility group-box) domain comprises one or more of:

(a) a polypeptide having at least 95% sequence identity to a polypeptide from about amino acid 6 to about amino acid 76 or from about amino acid 90 to about amino acid 138 of SEQ ID NO;

1;

(b) a polypeptide having at least 95% sequence identity to comprising a polypeptide from about amino acid 9 to about amino acid 76 or from about amino acid 95 to about amino acid 160 SEQ ID NO;

2;

(c) a polypeptide having at least 95% sequence identity to comprising a polypeptide from about amino acid 9 to about amino acid 75 or from about amino acid 98 to about amino acid 158 SEQ ID NO;

3;

or

(d) a polypeptide having at least 95% sequence identity to comprising a polypeptide from about amino acid 9 to about amino acid 75 or from about amino acid 93 to about amino acid 158 of SEQ ID NO;

4.

5. The method of claim 3, wherein the isolated or recombinant polypeptide is a mammalian polypeptide that is or is not post-translationally modified, a mammalian polypeptide that is or is not post-translationally alkylated, and a polypeptide expressed in a non-mammalian system.

6. The method of claim 5, wherein the mammalian polypeptide is a human polypeptide.

7. The method of claim 1, wherein the isolated or recombinant polypeptide comprising an HMG-box (high mobility group-box) domain comprises one or more of:

(a) a polypeptide comprising from about amino acid 6 to about amino acid 76 or from about amino acid 90 to about amino acid 138 of SEQ ID NO;

1;

(b) a polypeptide comprising from about amino acid 9 to about amino acid 76 or from about amino acid 95 to about amino acid 160 SEQ ID NO;

2;

(c) a polypeptide comprising nucleotides from about amino acid 9 to about amino acid 75 or from about amino acid 98 to about amino acid 158 SEQ ID NO;

3;

or

(d) a polypeptide comprising nucleotides from about amino acid 9 to about amino acid 75 or from about amino acid 93 to about amino acid 158 of SEQ ID NO;

4.

8. The method of claim 1, wherein the isolated or recombinant polypeptide comprising the HMG-box domain comprises one or more of:

(a) an isolated or recombinant polypeptide high mobility group box 1 (HMGB1) consisting of from about amino acid 6 to about amino acid 76 of SEQ ID NO;

1 or a polypeptide having at least 90% sequence identity thereto;

(b) an isolated or recombinant polypeptide high mobility group box 2 (HMGB2) consisting of from about amino acid 9 to about amino acid 76 of SEQ ID NO;

2 or a polypeptide having at least 90% sequence identity thereto;

(c) an isolated or recombinant polypeptide high mobility group box 3 (HMGB3) consisting of from about amino acid 9 to about amino acid 75 of SEQ ID NO;

3 or a polypeptide having at least 90% sequence identity thereto;

or

(d) an isolated or recombinant polypeptide high mobility group box 4 (HMGB

     4) consisting of from about amino acid 9 to about amino acid 75 of SEQ ID NO;

4 or a polypeptide having at least 90% sequence identity thereto.

9. The method of claim 8, wherein the isolated or recombinant polypeptide is a mammalian polypeptide that is or is not post-translationally modified, a mammalian polypeptide that is or is not post-translationally alkylated, and a polypeptide expressed in a non-mammalian system.

10. The method of claim 9, wherein the mammalian polypeptide is a human polypeptide.

11. The method of claim 1 or 3, wherein the contacting is in vitro or in vivo.

12. The method of claim 8, wherein the contacting is in vitro or in vivo.