David P Donovan

US Patent:

7572602, Aug 11, 2009

Filed:

Dec 5, 2005

Appl. No.:

11/294156

Inventors:

David M. Donovan - Baltimore MD, US

Assignee:

The United States of America as represented by the Secretary of Agriculture - Washington DC

International Classification:

C07H 21/02
C07H 21/04
C12N 15/63
C12N 15/85
C12N 15/86
C12N 1/21
C12N 1/15
C12N 5/14
C12N 1/19
C12N 15/00
C12P 21/00

US Classification:

435 697, 536 232, 536 234, 536 237, 536 231, 4352523, 43525411, 4352542, 435325, 435419, 435 691, 435440, 435 701, 435 711, 4353201

Abstract:

The invention concerns a recombinant nucleic acid molecule encoding an antimicrobial fusion peptidoglycan endopeptidase. The recombinant nucleic acid molecule according to the invention is formed from a nucleic acid encoding a bacterial endopeptidase (lysostaphin) from and a nucleic acid encoding a second endopeptidase (endolysin) module from Group B streptococcal bacteriophage B30. The encoded fusion endopeptidase has antimicrobial activity and kills both bacteria and bacteria.

US Patent:

7982003, Jul 19, 2011

Filed:

Jul 6, 2009

Appl. No.:

12/498171

Inventors:

David M. Donovan - Baltimore MD, US

Assignee:

The United States of America as represented by the Secretary of Agriculture - Washington DC

International Classification:

C07K 1/00
C12N 9/00
C12N 9/14
C12N 9/48
C12N 9/52
A61K 38/43

US Classification:

530350, 435183, 435195, 435212, 435220, 424 941

Abstract:

The invention concerns a nucleic acid encoding a recombinant bifunctional fusion peptidoglycan hydrolase protein formed from a nucleic acid encoding a peptidoglycan hydrolase module and a nucleic acid encoding a second peptidoglycan hydrolase module. The fusion, dual (or multiples thereof) peptidoglycan hydrolase modules can be used to treat disease caused by the bacteria for which the individual modules of the fusion protein are specific.

US Patent:

8012730, Sep 6, 2011

Filed:

Aug 29, 2006

Appl. No.:

11/511848

Inventors:

David M. Donovan - Baltimore MD, US

Assignee:

The United States of America as represented by the Secretary of Agriculture - Washington DC

International Classification:

C12N 9/14
C07H 21/04

US Classification:

435195, 435183, 435325, 4352523, 536 231, 536 232

Abstract:

The bacteriophage phi11 endolysin has two peptidoglycan hydrolase domains (endopeptidase and amidase) and a SH3b cell wall-binding domain. In turbidity reduction assays, the purified protein can lyse untreated staphylococcal mastitis-causing pathogens, and coagulase negative staphylococci (, and ), making it a strong antimicrobial protein and an effective candidate for treating multidrug-resistant staphylococci. Lytic activity is maintained at the pH (6. 7) and the ‘free’ calcium concentration (3 mM) of milk. Truncated endolysin-derived proteins, containing just the endopeptidase domain, also lyse staphylococci, in the absence of the SH3b-binding domain.

US Patent:

8361772, Jan 29, 2013

Filed:

Jul 27, 2011

Appl. No.:

13/192150

Inventors:

David M. Donovan - Baltimore MD, US

Assignee:

The United States of America as Represented by the Secretary of Agriculture - Washington DC

International Classification:

C12N 9/14
A61K 38/46

US Classification:

435195, 435183, 530350, 424 946

Abstract:

The bacteriophage phi11 endolysin has two peptidoglycan hydrolase domains (endopeptidase and amidase) and a SH3b cell wall-binding domain. In turbidity reduction assays, the purified protein can lyse untreated staphylococcal mastitis-causing pathogens, and coagulase negative staphylococci (, and ), making it a strong antimicrobial protein and an effective candidate for treating multidrug-resistant staphylococci. Lytic activity is maintained at the pH (6. 7) and the ‘free’ calcium concentration (3 mM) of milk. Truncated endolysin-derived proteins, containing just the endopeptidase domain, also lyse staphylococci, in the absence of the SH3b-binding domain.

US Patent:

8383102, Feb 26, 2013

Filed:

May 21, 2010

Appl. No.:

12/784675

Inventors:

David Donovan - Baltimore MD, US

Assignee:

The United States of America as represented by the Secretary of Agriculture - Washington DC

International Classification:

A61K 38/54
C07H 21/04
C12N 15/63
C12N 5/10

US Classification:

424 943, 435188, 435455, 435325, 4353201, 536 232

Abstract:

Lysostaphin is a bacteriocin secreted by to kill , and has been shown to also be a potent antimicrobial for many antibiotic-resistant strains of. By adding a 13 amino acid protein transduction domain (PTD) from the HIV-TAT protein to lysostaphin to form lysostaphin-PTD, both extracellular and intracellular forms of and MRSA are killed in all (multiple) cell types examined.

US Patent:

8481289, Jul 9, 2013

Filed:

Jul 24, 2009

Appl. No.:

12/460812

Inventors:

David M. Donovan - Baltimore MD, US
Stephen C. Becker - Baltimore MD, US

Assignee:

The United States of America, as Represented by the Secretary of Agriculture - Washington DC

International Classification:

C12P 21/04

US Classification:

435 697

Abstract:

Multi-drug resistant superbugs are a persistent problem in modern health care. This invention provides an antimicrobial endolysin-Lysostaphin triple fusion protein, comprising (1) an endolysin CHAP endopeptidase domain, (2) an endolysin amidase domain, and (3) a Lysostaphin glycyl-glycine endopeptidase domain. The domains are derived from two proteins that show antimicrobial synergy when used in combination. The protein has specificity and exolytic activity for the peptidoglycan cell wall of untreated, live from many growth phases i. e. stationary, logarithmic and biofilm growth. The recombinant triple fusion protein comprising the three functional antimicrobial domains is designed to be refractory to resistance development.

US Patent:

8568714, Oct 29, 2013

Filed:

May 21, 2009

Appl. No.:

12/470466

Inventors:

David M. Donovan - Baltimore MD, US
Stephen C. Becker - Baltimore MD, US

Assignee:

The United States of America, as represented by the Secretary of Agriculture - Washington DC

International Classification:

A61K 38/46

US Classification:

424 946

Abstract:

Multi-drug resistant superbugs are a persistent problem in modern health care. LysK is a staphylococcal bacteriophage endolysin from the phage K. It is a peptidoglycan hydrolase enzyme that can lyse many staphylococcal strains and thus is a potent antimicrobial against , including MRSA. Lysostaphin is a bacteriocin secreted by to kill , and has been shown to also be a potent antimicrobial for many antibiotic resistant strains of. This study describes optimal reaction conditions for the recombinant His-tagged LysK protein, compares its MIC and antimicrobial activity to lysostaphin and demonstrates synergy when the two are used in combination against the MRSA USA300.

US Patent:

20120052546, Mar 1, 2012

Filed:

Sep 1, 2010

Appl. No.:

12/874138

Inventors:

Bruce S. Seal - Athens GA, US
Gregory R. Siragusa - Waukesha WI, US
Ibn Mustafa A. Simmons - Athens GA, US
Johnna K. Garrish - Hull GA, US
David M. Donovan - Baltimore MD, US

Assignee:

The United State of America, as represented by the Secretary of Agriculture - Washington DC

International Classification:

C12N 9/00
C07H 21/00

US Classification:

435183, 536 232

Abstract:

The present invention relates to isolated bacteriophage lytic enzymes from baccteriophages CP26F and CP39O, and uses in controlling