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(12) United States Patent (10) Patent No.: US 8,003,323 B2 Morris Et Al

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(12) United States Patent (10) Patent No.: US 8,003,323 B2 Morris Et Al US008003323B2 (12) United States Patent (10) Patent No.: US 8,003,323 B2 Morris et al. (45) Date of Patent: *Aug. 23, 2011 (54) REDUCTION IN BACTERIAL FOREIGN PATENT DOCUMENTS COLONIZATION BY ADMINISTERING DE 3714699 1, 1988 BACTERIOPHAGE COMPOSITIONS DE 19828,596 2, 1999 EP O 29O 295 11, 1988 EP O 414 304 2, 1991 (75) Inventors: J. Glenn Morris, Baltimore, MD (US); EP O 510907 10, 1992 Alexander Sulakvelidze, Towson, MD GB 2 253859 9, 1992 (US); Zemphira Alavidze, Tbilisi (GE): JP 62-123104 6, 1987 WO WO90, 13631 11, 1990 Gary R. Pasternack, Baltimore, MD WO WO95/27043 10, 1995 (US); Torrey C. Brown, Severna Park, WO WO 97.39.111 10, 1997 MD (US) WO WOOOf 69269 11, 2000 (73) Assignee: Intralytix, Inc., Baltimore, MD (US) OTHER PUBLICATIONS Bolder et al. The effect of flavophospholipol (Flavomycin) and (*) Notice: Subject to any disclaimer, the term of this Salinomycin Sodium (Sacox) on the excretion of Clostridium patent is extended or adjusted under 35 perfiringens, Salmonella enteritidis, and Campylobacter jejuni in U.S.C. 154(b) by 0 days. broilers after experimental infection. Poult Sci. Dec. This patent is Subject to a terminal dis 1999;78(12): 1681-9.* claimer. Smith et al. Factors Influencing the Survival and Multiplication of Bacteriophages in Calves and in Their Environment. Journal of Gen Appl. No.: 12/264,582 eral Microbiology 133 (1987), 1127-1135.* (21) Adamia, Revaz S., et al., “The Virulent Bacteriophage IRA of Sal monella typhimurium: Cloning of Phage Genes which are Potentially (22) Filed: Nov. 4, 2008 Lethal for the Host Cell”, J Basic Microbiol., vol. 30, p. 707-716, 1990. (65) Prior Publication Data Alavidze, A., et al., “Isolationof Specific Lytic Phages Multidrug US 2009/0053144A1 Feb. 26, 2009 Resistant Pseudomonas aeruginosa'. The American Society for Microbiology, vol. 99, p. 447, 1999. Alavidze, Z. et al., “Isolation of Specific Lytic Phases against Related U.S. Application Data Multidrug Resistant Pseudomonas aeraiginosa, American Society for Microbiology, Final Program, 1999. (63) Continuation of application No. 107724.900, filed on Barrow, et al., “Salmonellosis—Prospects for Microbiological Con Dec. 2, 2003, now Pat. No. 7,459.272, which is a trol in Poultry”, Avian Pathology, vol. 18, p. 557-561, 1989. continuation of application No. 09/757,685, filed on Barrow, et. al., Use of Lytic Bacteriophage for Control of Experimen Jan. 11, 2001, now abandoned. tal Escherichia coli Septicemia and Meningitis in Chickens and Calves. Clinical and Diagnostic Laboratory Immunology 5(3): 294 (60) Provisional application No. 60/175.377, filed on Jan. 298. 1998. Barrow, P. A., “Bacteriophages Mediating Somatic 11, 2000, provisional application No. 60/175,415, Antigenic Conversion in Salmonella cholerae-suis: their Isolation filed on Jan. 11, 2000, provisional application No. from Sewage and Other Salmonella Serotypes Processing the 60/175,416, filed on Jan. 11, 2000, provisional Somatic 6 Antigen”, Journal of General Microbiology, vol. 132, p. application No. 60/205.240, filed on May 19, 2000. 835-837, 1986. (51) Int. C. (Continued) CI2O I/68 (2006.01) Primary Examiner — Michele Joike A6 IK35/00 (2006.01) (74) Attorney, Agent, or Firm — Hunton & Williams LLP (52) U.S. Cl. ........................................... 435/6; 424/93.1 (58) Field of Classification Search ........................ None (57) ABSTRACT See application file for complete search history. The present invention provides a method for reducing the risk of bacterial infection or sepsis in a susceptible patient by (56) References Cited treating the Susceptible patient with a pharmaceutical com U.S. PATENT DOCUMENTS position containing bacteriophage of one or more strains 4,375,734 A 3, 1983 Kozloff et al. which produce lytic infections in pathogenic bacteria. Pref 4,891,210 A 1, 1990 Norris erably, treatment of the patient reduces the level of coloniza 4,957,686 A 9, 1990 Norris tion with pathogenic bacteria Susceptible to the bacteriophage 5,132,221 A 7, 1992 Ward et al. by at least one log. In a typical embodiment, the Susceptible 5,612, 182 A 3, 1997 Pearson et al. patient is an immunocompromised patient selected from the 5,641,464 A 6/1997 Briggs, III et al. group consisting of leukemia patients, lymphoma patients, 5,660,812 A 8, 1997 Merrill et al. 5,688,501 A 11/1997 Merrilet al. carcinoma patients, sarcoma patients, allogeneic transplant 5,766,892 A 6, 1998 Merrill et al. patients, congenital or acquired immunodeficiency patients, 5,811,093 A 9, 1998 Merrill et al. cystic fibrosis patients, and AIDS patients. In a preferred 6,015,816 A 1/2000 Kostyniak et al. mode, the patients treated by this method are colonized with 6,056,954 A 5, 2000 Fischetti et al. 6,121,036 A 9, 2000 Ghanbari et al. the pathogenic bacteria Subject to infection by said bacte 6,322,783 B1 1 1/2001 Takahashi riophage. 6,942,858 B1* 9/2005 Ghanbari et al. ............ 424,936 2005/0260171 A1 11/2005 Ghanbari et al. 35 Claims, No Drawings US 8,003,323 B2 Page 2 OTHER PUBLICATIONS Slopek, et al., “Results of Bacteriophage Treatment of Suppurative Barrow, Paul A., et al., “Bacteriophage Therpay and Prophylaxis: Bacterial Infections; IV. Evaluation of the Results Obtained in 370 Rediscovery and Renewed Assessment of Potential”. Trends in cases”. Arch. Immunol. Therapiae Exper, vol. 33, p. 219-240, 1985. Microbiology, vol. 5, p. 268-271, 1997. Slopek, et al., “Results of Bacteriophage Treatment of Suppurative Berchieri, A., Jr., et al., The Activity in the Chicken Alimentary Tract Bacterial Infections; V. Evaluation of the Results Obtained I Chil of Bacteriophages Lytic for Salmonella typhimurium, Res. dren'. Arch. Immunol. Therapiae Exper, vol. 33, p. 241-260, 1985. Microbiol., vol. 142, p. 541-549, 1991. Slopek, et al., “Results of Bacteriophage Treatment of Suppurative Bogovazova, G. G. et al., “Immunobiological Properties & Thera Bacterial Infections: VI. Analysis of Treatment of Suppurative peutic Effectiveness of Preparations from Klebsiella Bacterioph Staphylococcal Infections'. Arch. Immunol. Therapiae Exper... vol. ages”, Zh. Mikrobiol. Epidemiol. Immunobiol., vol. 3, p. 30-33, 33, p. 261-275, 1985. 1992. Slopek, et al., “Results of Bacteriophage Treatment of Suppurative Carlton, R., Phage Therapy: Past History and Future Prospects Bacterial Infections in the Years 1981-1986', Arch. Immunol. Archivum Immunologiae et Therapiae Experimentalis 47: 267-274, Therapiae Exper, vol. 35, p. 569-584, 1987. 1999. Slopek, et al., Results of Bacteriophage Treatment of Suppurative Gachechiladze, K. K., et al., “Host-Controlled Modification and Bacterial Infections; II. Detailed Evaluation of the Results, Arch. Restriction as a Criterion of Evaluating the Therapeutical Potential of Immunol. Therapiae Exper, vol. 31, p. 293-327, 1981. Pseudomonas Phage'. J. Basic Microbiol., vol. 31, p. 101-106, 1991. Slopek, S., et al., “Results of Bacteriophage Treatment of Suppura Karin E. Byers et al., “Disinfection of Hospital Rooms Contaminated tive Bacterial Infections VI. Analysis of Treatment of Supparative with Vancomyci-Resistant Enterococcus faecum”, col. 4, p.261-264. Staphylococcal Infections'. Database Biosis 'Online, Biosciences Apr. 1988. Information Service, 1985. Kudva, Indira T., et al., "Biocontrol of Escherichia coli O157 with Soothill, J. S., “Bacteriophage Prevents Destruction of Skin Graft by O157-Specific Bacteriophages'. Applied and Environmental Pseudomonas aeruginosa'. Bums, vol. 20, p. 209-211, 1994. Microbiology, vol. 65, p. 3767-3773, 1999. Soothill, J. S., et al., “The Efficacy of Phages in the Prevention of the Lenski, Richard E., “Dynamics of Interactions Between Bacteria and Destruction of PigSkin invitro by Pseudomonas aerarginosa”. Med. Virulent Bacteriphage'. Adv. Microb. Ecol., vol. 10, p. 1-44, 1988. Sci. Res., vol. 16, p. 1287-1288, 1988. Levin, Bruce R. et al., “Phage Therapy Revisited: The Population Soothill, J.S., "Treatment of Experimental Infections of Mice with Biology of a Bacterial Infection and its Treatment with Bacterioph Bacteriophages”. J. Med. Microbiol., vol. 37, p. 258-261, 1992. age and Antibiotics”. The American Naturalist, vol. 147, p. 881-898, Williams Smith, H., et al., “Effectiveness of Phages in Treating 1996. Experimental Escherichia coil Diarrhoea in Calves, Piglets and Ochs, Hans D., “Immunologic Responses to Bacteriophage (bX 174 Lambs”, Journal of General Microbiology, vol. 129, p. 2659-2675, in Immunodeficiency Diseases”. The Journal of Clinical Investiga 1983. tion, vol. 50, p. 2559-2567, 1971. Williams Smith, H., et al., “Effectiveness of Phages in Treating Risi, et al. Prevention of Infection in the Immunocompromised host, Experimental Escherichia coli Diarrhoea in Calves by Means of American Jouranl Infect. Control 26: 594-604, 1998. Bacteriophages”. Journal of General Microbiology, vol. 133, p. Slopek, et al., “Results of Bacteriophage Treatment of Suppurative 1111-1126, 1987. Bacterial Infections; I. General Evaluation of the Results’. Arch. Williams Smith, H., et al., “Successful Treatment of Experimental Immunol. Therapiae Exper, vol. 31, p. 267-291, 1983. Escherichia coli Infections in Mice Using Phage: Its General Supe Slopek, et al., “Results of Bacteriophage Treatment of Suppurative riority Over Antibiotics”,Journal of General Microbiology, vol. 128, Bacterial Infections; III. Detailed Evaluation of the Results Obtained p. 307-318, 1982. in Further 150 cases”. Ach. Immunol. Therapiae Exper, vol. 32, p. 317-335, 1984. * cited by examiner US 8,003,323 B2 1. 2 REDUCTION IN BACTERIAL trations.” Arch. Intern: Med., 126: 255-9). However, during COLONIZATION BY ADMINISTERING the 1980's enterococcal strains with high levels of aminogly BACTERIOPHAGE COMPOSITIONS coside resistance and resistance to penicillin, mediated both by a plasmid-encoded B-lactamase and by changes in peni RELATED APPLICATIONS cillin binding proteins, appeared (Mederski-Samoraj, et al. (1983), “High level resistance to gentamicin in clinical iso This application is a Continuation of U.S. patent applica lates of enterococci.” J. Infect. Dis., 147:751-7: Uttley, et al. tion Ser. No. 107724,900, filed on Dec. 2, 2003, now U.S. Pat. (1988), “Vancomycin resistant enterococci.” Lancet i:57-8).
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