Minocycline compounds for biodefense

Abstract

Methods of treating or preventing a bacterial infection in a subject are disclosed herein, wherein the bacterial infection is caused by a bacterium which can be used as a biological weapon. Also disclosed is a pharmaceutical composition comprising the compound of the present invention for treating or preventing a bacterial infection in a subject, wherein the bacterial infection is caused by a bacterium which can be used as a biological weapon.

1 . A method of treating a bacterial infection in a subject in need thereof, said method comprising administering to said subject an effective amount of a compound, or a salt thereof, at a dose of about 10 mg to about 1000 mg, wherein the compound is Compound A′ of the following structural formula: 
       
         
           
           
               
               
           
         
         wherein said bacterial infection is caused by a bacterium which can be used as a biological weapon, such that said infection in said subject is treated. 
       
     
     
         2 . The method of  claim 1 , wherein the compound is Compound A of the following structural formula: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 1 , wherein the bacterium is resistant to antibiotics that are typically used to treat infections caused by the bacterium. 
     
     
         4 . The method of  claim 1 , wherein the bacterium is in the form of a powder or an aerosol. 
     
     
         5 . The method of  claim 1 , wherein the bacterium is able to form spores. 
     
     
         6 . The method of  claim 1 , wherein the bacterium is selected from the group comprising:
 a bacterium belonging to the species  Franciscella tularensis, Clostridium botulinum, Yersinia pestis, Burkholderia mallei, Burkholderia pseudomallei, Coxiella burnetii, Chlamydia psittaci, Clostridium perfringens, Rickettsia prowazekii, Campylobacter jejuni, Yersinia enterocolitica, Listeria monocytogenes;      a bacterium belonging to the genus  Bacillus  (e.g.,  B. anthracis , including Multi-Drug Resistant (MDR) anthrax strains),  Brucella  (e.g.,  B. abortus, B. canis, B. ceti, B. inopinata, B. melitensis, B. microti, B. neotomae, B. ovis, B. pinnipedialis, B. suis ),  Shigella  (e.g.,  S. boydii, S. dysenteriae, S. flexneri  and  S. sonnei ),  Vibrio  (e.g.,  V. cholerae ),  Salmonella  (e.g.,  S. bongori  and  S. enterica ); and
 a bacterium belonging to a diarrheagenic strain of  E. coli.    
   
     
     
         7 . The method of  claim 6 , wherein the bacterium is selected from the group comprising:
 a bacterium belonging to the species  Franciscella tularensis, Yersinia pestis, Burkholderia mallei, Burkholderia pseudomallei, Rickettsia prowazekii ; and   a bacterium belonging to the genus  Bacillus  (e.g.,  B. anthracis , including Multi-Drug Resistant (MDR) anthrax strains).   
     
     
         8 . The method of  claim 1 , wherein the bacterium is selected from the group consisting of:
 a bacterium belonging to the species  Franciscella tularensis, Clostridium botulinum, Yersinia pestis, Burkholderia mallei, Burkholderia pseudomallei, Coxiella burnetii, Chlamydia psittaci, Clostridium perfringens, Rickettsia prowazekii, Campylobacter jejuni, Yersinia enterocolitica, Listeria monocytogenes;      a bacterium belonging to the genus  Bacillus  (e.g.,  B. anthracis , including Multi-Drug Resistant (MDR) anthrax strains),  Brucella  (e.g.,  B. abortus, B. canis, B. ceti, B. inopinata, B. melitensis, B. microti, B. neotomae, B. ovis, B. pinnipedialis, B. suis ),  Shigella  (e.g.,  S. boydii, S. dysenteriae, S. flexneri  and  S. sonnei ),  Vibrio  (e.g.,  V. cholerae ),  Salmonella  (e.g.,  S. bongori  and  S. enterica ); and
 a bacterium belonging to a diarrheagenic strain of  E. coli.    
   
     
     
         9 . The method of  claim 8 , wherein the bacterium is selected from the group consisting of:
 a bacterium belonging to the species  Franciscella tularensis, Yersinia pestis, Burkholderia mallei, Burkholderia pseudomallei, Rickettsia prowazekii ; and   a bacterium belonging to the genus  Bacillus  (e.g.,  B. anthracis , including Multi-Drug Resistant (MDR) anthrax strains).   
     
     
         10 . The method of  claim 1 , wherein the bacterium is selected from the group consisting of:  Yersinia pestis, Burkholderia mallei  and  Bacillus anthracis.    
     
     
         11 . The method of  claim 1 , wherein the compound is administered once per day or twice per day. 
     
     
         12 . The method of  claim 1 , wherein the compound is administered intravenously or orally. 
     
     
         13 . The method of  claim 1 , wherein the compound is administered intravenously at the dose of about 50 mg to about 200 mg. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 1 , wherein the compound is administered orally at the dose of about 100 to about 300 mg. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the method comprises administering the compound for at least 3 days, at least 7 days, at least 14 days, at least 21 days, at least 30 days or at least 60 days. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the method comprises administering to the subject one or more loading doses of the compound, followed by one or more maintenance doses of the compound. 
     
     
         20 . The method of  claim 19 , wherein the one or more loading dose is greater than the one or more maintenance dose. 
     
     
         21 . The method of  claim 19 , wherein the loading dose is intravenous and the maintenance dose is oral. 
     
     
         22 . The method of  claim 1 , wherein the subject is a human. 
     
     
         23 . A method of preventing a bacterial infection in a subject in need thereof, said method comprising administering to said subject an effective amount of a compound, or a salt thereof, at a dose of about 10 mg to about 1000 mg, wherein the compound is Compound A′ of the following structural formula: 
       
         
           
           
               
               
           
         
         wherein said bacterial infection is caused by a bacterium which can be used as a biological weapon, such that said infection in said subject is prevented. 
       
     
     
         24 - 44 . (canceled)