US2003017494A1PendingUtilityA1

Genes encoding mycobacterial proteins associated with cell binding and cell entry and uses thereof

Priority: Jul 10, 1996Filed: Jun 24, 2002Published: Jan 23, 2003
Est. expiryJul 10, 2016(expired)· nominal 20-yr term from priority
A61K 39/00A61K 48/00C07K 14/35
57
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Claims

Abstract

A gene from a strain of Mycobacterium encoding a protein of molecular weight between about 45 to about 60 kDa and associated with cell binding and cell entry was cloned. The genes and encoded protein have utility in immunogenic preparations or diagnostic applications.

Claims

exact text as granted — not AI-modified
What we claim is:  
     
         1 . An isolated nucleic acid molecule encoding a mycobacterial protein associated with cell binding and cell entry of a Mycobacterium strain and having a molecular weight of about 45 to about 60 kDa.  
     
     
         2 . The nucleic acid molecule of  claim 1  wherein said Mycobacterium species is a species of the tuberculosis complex.  
     
     
         3 . The nucleic acid molecule of  claim 2  wherein said Mycobacterium strain is a strain of  Mycobacterium tuberculosis.    
     
     
         4 . The nucleic acid molecule of  claim 2  wherein said Mycobacterium strain is a strain of  Mycobacterium bovis.    
     
     
         5 . The nucleic acid molecule of  claim 1  wherein said mycobacterial protein has substantially the following amino acid composition:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                     
                   Number of 
                     
                 
                     
                   Amino Acids 
                   Residues 
                 
                     
                     
                 
                     
                 
                 
                 
                 
                 
               
                     
                   Leucine 
                     
                   53 
                 
                     
                   Arginine 
                     
                   32 
                 
                     
                   Threonine 
                     
                   45 
                 
                     
                   Alanine 
                     
                   60 
                 
                     
                   Valine 
                     
                   40 
                 
                     
                   Serine 
                     
                   43 
                 
                     
                   Proline 
                     
                   38 
                 
                     
                   Aspartic Acid 
                   29 
                 
                     
                   Isoleucine 
                     
                   24 
                 
                     
                   Asparagine 
                     
                   23 
                 
                     
                   Tyrosine 
                     
                   16 
                 
                     
                   Glycine 
                     
                   45 
                 
                     
                   Phenylalanine 
                   14 
                 
                     
                   Glutamic Acid 
                   15 
                 
                     
                   Lysine 
                     
                   15 
                 
                     
                   Glutamine 
                     
                   12 
                 
                     
                   Tryptophan 
                     
                    7 
                 
                     
                   Methionine 
                     
                    7 
                 
                     
                   Cysteine 
                     
                    6 
                 
                     
                   Histidine 
                     
                    3 
                 
                     
                     
                 
                     
                     
                 
             
                
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         6 . The nucleic acid molecule of  claim 1  having a restriction map substantially as shown in FIG. 5 for  M. bovis  strain BCG or the corresponding restriction map from other mycobacteria from the tuberculosis complex.  
     
     
         7 . The nucleic acid molecule of  claim 1  having a DNA sequence as shown in FIG. 6 (SEQ ID No: 2) for  M. bovis  strain BCG or the sequence of the corresponding gene of other mycobacteria from the tuberculosis complex.  
     
     
         8 . The nucleic acid molecule of  claim 1  encoding an amino acid sequence as shown in FIG. 7 (SEQ ID No: 3) for  M. bovis  strain BCG or the corresponding sequence in other mycobacteria from the tuberculosis complex.  
     
     
         9 . An isolated DNA molecule amplifiable by polymerase chain reaction (PCR) by a pair of primers having the sequences of primers 4879 (SEQ ID No: 12) and 4882 (SEQ ID No: 15); or 4879 (SEQ ID No: 12) and 4865 (SEQ ID No: 11); or 4879 (SEQ ID No: 12) and 4812 (SEQ ID No: 10).  
     
     
         10 . The DNA molecule of  claim 9  from a Mycobacterium strain of the tuberculosis complex.  
     
     
         11 . The DNA molecule of  claim 9  from a Mycobacterium strain of  Mycobacterium tuberculosis.    
     
     
         12 . The DNA molecule of  claim 9  from a Mycobacterium strain of  Mycobacterium bovis.    
     
     
         13 . A vector for transformation of a host comprising the nucleic acid molecule of  claim 1  or the DNA molecule of  claim 9 .  
     
     
         14 . The vector of  claim 13  further comprising DNA sequences for expression of said protein in said host.  
     
     
         15 . A transformed host containing an expression vector as claimed in  claim 14 .  
     
     
         16 . A recombinant mycobacterial protein associated with cell binding and cell entry producible by the transformed host of  claim 15 .  
     
     
         17 . A plasmid containing the gene encoding a mycobacterial protein associated with cell binding and cell entry of a strain of Mycobacterium having the identifying characteristics of plasmid pBCGcepX having ATCC Deposit No. 97511.  
     
     
         18 . A method of determining the presence, in a sample, of nucleic acid encoding a mycobacterial protein associated with cell binding and cell entry and having a molecular weight between about 45 and about 60 kDa of a strain of Mycobacterium, which comprises the steps of: 
 (a) contacting the sample with the nucleic acid molecule of  claim 1  or the DNA molecule of  claim 9  to produce duplexes comprising the nucleic acid molecule or DNA molecule and any nucleic acid molecule encoding the protein present in the sample and specifically hybridizable therewith; and    (b) determining production of the duplexes.    
     
     
         19 . A diagnostic kit for determining the presence, in a sample, of nucleic acid encoding a mycobacterial protein associated with cell binding and cell entry and having a molecular weight of between about 45 and about 60 kDa of a strain of Mycobacterium, comprising: 
 (a) the nucleic acid molecule of  claim 1  or the DNA molecule of claim  9 ;    (b) contacting means to contact the nucleic acid molecule or DNA molecule with the sample to produce duplexes comprising the nucleic acid molecule or DNA molecule and any nucleic acid molecule encoding the protein present in the sample and hybridizable with the nucleic acid or DNA molecule; and    (c) identifying means to determine production of the duplexes.    
     
     
         20 . A method for detection of a strain of Mycobacterium in a sample of tissue or body fluids, which comprises: 
 providing a pair of primers which are primers 4879 (SEQ ID No: 12) and 4882 (SEQ ID No: 15); or 4879 (SEQ ID No. 12) and 4865 (SEQ ID No: 11); or 4879 (SEQ ID No: 12) and 4812 (SEQ ID No: 10);    contacting the sample with the probes;    performing a polymerase chain reaction to amplify an amplifiable nucleic acid sequence encoding a mycobacterial protein associated with cell binding or cell entry; and    detecting the amplified DNA sequence which indicates the presence of a strain of Mycobacterium in the sample.    
     
     
         21 . An oligonucleotide primer selected from the group consisting of primers 4879 (SEQ ID No: 12), 4882 (SEQ ID No: 15), 4865 (SEQ ID No: 11) and 4812 (SEQ ID No: 10).  
     
     
         22 . A method of producing a substantially pure recombinant mycobacterial protein associated with cell binding and cell entry and having a molecular weight between about 45 kDa and 60 kDa, which comprises: 
 transforming a host with a vector as claimed in claim  14 ; growing the transformed host to express the protein, and isolating and purifying the protein free from other proteinaceous and cellular material.    
     
     
         23 . An isolated and purified mycobacterial protein associated with cell binding and cell entry of a Mycobacterium strain and having a molecular weight of between about 45 and about 60 kDa.  
     
     
         24 . The protein of  claim 23  which is that of a Mycobacterium strain of the tuberculosis complex.  
     
     
         25 . The protein of  claim 23  which is that of a Mycobacterium strain of  Mycobacterium tuberculosis.    
     
     
         26 . The protein of  claim 23  which is that of a strain of  Mycobacterium bovis.    
     
     
         27 . The protein of  claim 23  produced by the procedure of  claim 22 .  
     
     
         28 . The protein of  claim 23  having substantively the following amino acid composition:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                     
                 
                     
                     
                   Number of 
                     
                 
                     
                   Amino Acids 
                   Residues 
                 
                     
                     
                 
                     
                 
                 
                 
                 
                 
               
                     
                   Leucine 
                     
                   53 
                 
                     
                   Arginine 
                     
                   32 
                 
                     
                   Threonine 
                     
                   45 
                 
                     
                   Alanine 
                     
                   60 
                 
                     
                   Valine 
                     
                   40 
                 
                     
                   Serine 
                     
                   43 
                 
                     
                   Proline 
                     
                   38 
                 
                     
                   Aspartic Acid 
                   29 
                 
                     
                   Isoleucine 
                     
                   24 
                 
                     
                   Asparagine 
                     
                   23 
                 
                     
                   Tyrosine 
                     
                   16 
                 
                     
                   Glycine 
                     
                   45 
                 
                     
                   Phenylalanine 
                   14 
                 
                     
                   Glutamic Acid 
                   15 
                 
                     
                   Lysine 
                     
                   15 
                 
                     
                   Glutamine 
                     
                   12 
                 
                     
                   Tryptophan 
                     
                    7 
                 
                     
                   Methionine 
                     
                    7 
                 
                     
                   Cysteine 
                     
                    6 
                 
                     
                   Histidine 
                     
                    3 
                 
                     
                     
                 
                     
                     
                 
             
                
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         29 . An immunogenic composition, comprising at least one component selected from the group consisting of at least one isolated nucleic acid molecule as claimed in  claim 1 , at least one isolated DNA molecule as claimed in  claim 9 , at least one recombinant mycobacterial protein as claimed in  claim 16  and at least one protein as claimed in  claim 23  as an active component thereof, and a pharmaceutically acceptable carrier therefor.  
     
     
         30 . A method of generating an immune response in a host, which comprises administering to the host an immunoeffective amount of the immunogenic composition of claim  29 .

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