US2006263376A1PendingUtilityA1

Pharmaceutical composition comprising PIM-activated NKT cells, and use thereof in therapy

Assignee: INST NAT SANTE RECH MEDPriority: Apr 19, 1999Filed: Apr 11, 2006Published: Nov 23, 2006
Est. expiryApr 19, 2019(expired)· nominal 20-yr term from priority
A61P 35/00A61P 31/04A61K 31/685A61K 35/17
44
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Claims

Abstract

The invention concerns a pharmaceutical composition comprising at least a PIM-activated NKT cell and the use of at least one PIM and/or a PIM-activated NKT cell for treating a disease for which a granulomatous type of immune response is desired.

Claims

exact text as granted — not AI-modified
1 - 12 . (canceled)  
     
     
         13 . An isolated NKT cell, wherein said cell has been activated by at least one phosphatidylinositol mannoside (PIM).  
     
     
         14 . An isolated NKT cell as claimed in  claim 13 , further comprising a pharmaceutically acceptable vehicle.  
     
     
         15 . An isolated NKT cell as claimed in  claim 13 , wherein said PIM is of mycobacterial origin.  
     
     
         16 . An isolated NKT cell as claimed in  claim 13 , wherein said PIM is obtained from  Mycobacterium tuberculosis.    
     
     
         17 . An isolated NKT cell as claimed in  claim 13 , wherein said PIM comprises 4, 5, or 6 mannose units.  
     
     
         18 . An isolated NKT cell as claimed in  claim 13 , wherein said PIM comprises the formula:  
       
         
           
           
               
               
           
         
       
       wherein: 
 R 1  is a hydroxyl group or a (Man) x  group,  
 R 2  is a hydroxyl group or a (Man) x  group,  
 R 3  is a hydroxyl group or a (Man) x  group,  
 R 4  is a hydroxyl group or a (Man) x  group,  
 R 5  is a hydroxyl group or a (Man) x  group,  
 R 6  is optionally a fatty acid residue, and  
 R 7  is optionally a fatty acid residue;  
 and wherein said (Man) x  group is at least one mannoside group linked to inositol and x is the number of mannose units attached to one another in linear fashion.  
 
     
     
         19 . An isolated NKT cell as claimed in  claim 18 , wherein the number of mannose units is 1, 2, 3, 4, 5, or 6.  
     
     
         20 . An isolated NKT cell as claimed in  claim 18 , wherein the fatty acid residue comprises 18 to 24 carbon atoms.  
     
     
         21 . An isolated NKT cell as claimed in  claim 18 , wherein the fatty acid residue lacks a double bond.  
     
     
         22 . An isolated NKT cell as claimed in  claim 18 , wherein the fatty acid residue lacks a polar substituent.  
     
     
         23 . An isolated NKT cell as claimed in  claim 18 , wherein any two of R 1 , R 2 , R 3 , R 4 , and R 5  are each said (Man) x  group and the remaining three groups are each said hydroxyl group.  
     
     
         24 . An isolated NKT cell as claimed in  claim 23 , wherein the two (Man) x  groups are adjacent to one another.  
     
     
         25 . An isolated NKT cell as claimed in  claim 18 , wherein: 
 R 1  is a hydroxyl group,    R 2  is a (Man) x  group,    R 3  is a (Man) x  group,    R 4  is a hydroxyl group, and    R 5  is a hydroxyl group.    
     
     
         26 . An isolated NKT cell as claimed in  claim 18 , wherein: 
 R 1  is a hydroxyl group,    R 2  is a (Man) x  group, wherein x is 1,    R 3  is a (Man) x  group, wherein x is 1, 2, 3, 4, 5, or 6,    R 4  is a hydroxyl group, and    R 5  is a hydroxyl group.    
     
     
         27 . A pharmaceutical composition comprising at least one phosphatidylinositol mannoside (PIM)-activated NKT cell and a pharmaceutically acceptable vehicle.  
     
     
         28 . A pharmaceutical composition as claimed in  claim 27 , wherein said PIM is of mycobacterial origin.  
     
     
         29 . A pharmaceutical composition as claimed in  claim 27 , wherein said PIM is obtained from  Mycobacterium tuberculosis.    
     
     
         30 . A pharmaceutical composition as claimed in  claim 27 , wherein said PIM comprises 4, 5, or 6 mannose units.  
     
     
         31 . A pharmaceutical composition as claimed in  claim 27 , wherein said PIM comprises the formula:  
       
         
           
           
               
               
           
         
       
       wherein: 
 R 1  is a hydroxyl group or a (Man) x  group,  
 R 2  is a hydroxyl group or a (Man) x  group,  
 R 3  is a hydroxyl group or a (Man) x  group,  
 R 4  is a hydroxyl group or a (Man) x  group,  
 R 5  is a hydroxyl group or a (Man) x  group,  
 R 6  is optionally a fatty acid residue, and  
 R 7  is optionally a fatty acid residue;  
 and wherein said (Man) x  group is at least one mannoside group linked to inositol and x is the number of mannose units attached to one another in linear fashion.  
 
     
     
         32 . A pharmaceutical composition as claimed in  claim 31 , wherein the number of mannose units is 1, 2, 3, 4, 5, or 6.  
     
     
         33 . A pharmaceutical composition as claimed in  claim 31 , wherein the fatty acid residue comprises 18 to 24 carbon atoms.  
     
     
         34 . A pharmaceutical composition as claimed in  claim 31 , wherein the fatty acid residue lacks a double bond.  
     
     
         35 . A pharmaceutical composition as claimed in  claim 31 , wherein the fatty acid residue lacks a polar substituent.  
     
     
         36 . A pharmaceutical composition as claimed in  claim 31 , wherein any two of R 1 , R 2 , R 3 , R 4 , and R 5  are each said (Man) x  group and the remaining three groups are each said hydroxyl group.  
     
     
         37 . A pharmaceutical composition as claimed in  claim 36 , wherein the two (Man) x  groups are adjacent to one another.  
     
     
         38 . A pharmaceutical composition as claimed in  claim 31 , wherein: 
 R 1  is a hydroxyl group,    R 2  is a (Man) x  group,    R 3  is a (Man) x  group,    R 4  is a hydroxyl group, and    R 5  is a hydroxyl group.    
     
     
         39 . A pharmaceutical composition as claimed in  claim 31 , wherein: 
 R 1  is a hydroxyl group,    R 2  is a (Man) x  group, wherein x is 1,    R 3  is a (Man) x  group, wherein x is 1, 2, 3, 4, 5, or 6,    R 4  is a hydroxyl group, and    R 5  is a hydroxyl group.    
     
     
         40 . A method of treating a disease in a human in which an immune reaction of the granulomatous type is desired, comprising administering to the human at least one phosphatidylinositol mannoside (PIM), at least one PIM-activated NKT cell, or at least one PIM and at least one PIM-activated NKT cell.  
     
     
         41 . A method of treating a disease in a human as claimed in  claim 40 , wherein said PIM is of mycobacterial origin.  
     
     
         42 . A method of treating a disease in a human as claimed in  claim 40 , wherein said PIM is obtained from  Mycobacterium tuberculosis.    
     
     
         43 . A method of treating a disease in a human as claimed in  claim 40 , wherein said PIM comprises 4, 5, or 6 mannose units.  
     
     
         44 . A method of treating a disease in a human as claimed in  claim 40 , wherein said PIM comprises the formula:  
       
         
           
           
               
               
           
         
       
       wherein: 
 R 1  is a hydroxyl group or a (Man) x  group,  
 R 2  is a hydroxyl group or a (Man) x  group,  
 R 3  is a hydroxyl group or a (Man) x  group,  
 R 4  is a hydroxyl group or a (Man) x  group,  
 R 5  is a hydroxyl group or a (Man) x  group,  
 R 6  is optionally a fatty acid residue, and  
 R 7  is optionally a fatty acid residue;  
 and wherein said (Man) x  group is at least one mannoside group linked to inositol and x is the number of mannose units attached to one another in linear fashion.  
 
     
     
         45 . A method of treating a disease in a human as claimed in  claim 44 , wherein the number of mannose units is 1, 2, 3, 4, 5, or 6.  
     
     
         46 . A method of treating a disease in a human as claimed in  claim 44 , wherein the fatty acid residue comprises 18 to 24 carbon atoms.  
     
     
         47 . A method of treating a disease in a human as claimed in  claim 44 , wherein the fatty acid residue lacks a double bond.  
     
     
         48 . A method of treating a disease in a human as claimed in  claim 44 , wherein the fatty acid residue lacks a polar substituent.  
     
     
         49 . A method of treating a disease in a human as claimed in  claim 44 , wherein any two of R 1 , R 2 , R 3 , R 4 , and R 5  are each said (Man) x  group and the remaining three groups are each said hydroxyl group.  
     
     
         50 . A method of treating a disease in a human as claimed in  claim 49 , wherein the two (Man) x  groups are adjacent to one another.  
     
     
         51 . A method of treating a disease in a human as claimed in  claim 44 , wherein: 
 R 1  is a hydroxyl group,    R 2  is a (Man) x  group,    R 3  is a (Man) x  group,    R 4  is a hydroxyl group, and    R 5  is a hydroxyl group.    
     
     
         52 . A method of treating a disease in a human as claimed in  claim 44 , wherein: 
 R 1  is a hydroxyl group,    R 2  is a (Man) x  group, wherein x is 1,    R 3  is a (Man) x  group, wherein x is 1, 2, 3, 4, 5, or 6,    R 4  is a hydroxyl group, and    R 5  is a hydroxyl group.    
     
     
         53 . A method of treating a disease in a human as claimed in  claim 40 , wherein said disease is caused by an infection with a bacterial agent.  
     
     
         54 . A method of treating a disease in a human as claimed in  claim 53 , wherein said bacterial agent is a mycobacteria.  
     
     
         55 . A method of treating a disease in a human as claimed in  claim 40 , wherein said disease is a cancer.  
     
     
         56 . A method of treating a disease in a human as claimed in  claim 40 , wherein said disease is a melanoma.

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