US2005181987A1PendingUtilityA1

Compositions and methods for treatment of cancer

Assignee: WISTAR INSTPriority: Nov 6, 1998Filed: Mar 16, 2005Published: Aug 18, 2005
Est. expiryNov 6, 2018(expired)· nominal 20-yr term from priority
A61K 38/12A61K 38/177A61K 38/10
49
PatentIndex Score
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Claims

Abstract

Compositions containing one or more peptido-mimetics or modified peptido-mimetics of a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier are useful for methods of reducing metastasis in a mammal and for inhibiting inflammatory response in a mammal. Particularly useful are embodiments in which the ligand is a Lewis antigen and/or the adhesion molecule is a selectin, e.g., E-selectin. Methods are disclosed for identifying peptido-mimetics of carbohydrate ligands, which may be involved in binding of tumor cells to other cells, such as endothelial cells.

Claims

exact text as granted — not AI-modified
1 . A composition comprising a peptido-mimetic of a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier.  
     
     
         2 . The composition according to  claim 1 , wherein said adhesion molecule is a selectin.  
     
     
         3 . The composition according to  claim 1 , wherein said ligand is a Lewis antigen.  
     
     
         4 . The composition according to  claim 3 , wherein the Lewis antigen is selected from the group consisting of SA-Le a , SA-LeX, and LeY.  
     
     
         5 . The composition according to  claim 2 , wherein said adhesion molecule is E-selectin and said ligand is SA-Le a  or SA-LeX.  
     
     
         6 . The composition according to  claim 5 , wherein said peptido-mimetic is selected form the group consisting of:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   DLWDFVVGKPAG, 
                   SEQ ID NO:63 
                     
                 
                     
                     
                 
                     
                   DLWDWVIGKPAG, 
                   SEQ ID NO:64 
                 
                     
                     
                 
                     
                   DLWDWVVAKPAG, 
                   SEQ ID NO:65 
                 
                     
                     
                 
                     
                   DLWDWVVSKPAG, 
                   SEQ ID NO:66 
                 
                     
                     
                 
                     
                   DLWDWVVEKPAG, 
                   SEQ ID NO:67 
                 
                     
                     
                 
                     
                   DLWDWVVDKPAG, 
                   SEQ ID NO:68 
                 
                     
                     
                 
                     
                   DLWDWVVGEPAG, 
                   SEQ ID NO:69 
                 
                     
                     
                 
                     
                   DLWDWVVGDPAG, 
                   SEQ ID NO:70 
                 
                     
                     
                 
                     
                   DLWDWVVGKEAG, 
                   SEQ ID NO:71 
                 
                     
                     
                 
                     
                   DLWDWVVGKDAG, 
                   SEQ ID NO:72 
                 
                     
                     
                 
                     
                   DLWDWVVGKPDG, 
                   SEQ ID NO:73 
                 
                     
                     
                 
                     
                   DLWDWVVGKPAD, 
                   SEQ ID NO:74 
                 
                     
                     
                 
                     
                   DLWDWVKEKPAG, 
                   SEQ ID NO:75 
                 
                     
                     
                 
                     
                   DLWDWVLAKPAG, 
                   SEQ ID NO:76 
                 
                     
                     
                 
                     
                   DLWDWVVGEDAG, 
                   SEQ ID NO:77 
                 
                     
                     
                 
                     
                   DLWDWVVGKPEK 
                   SEQ ID NO:78 
                 
                     
                     
                 
                     
                   DLWDWVKEEPAG, 
                   SEQ ID NO:79 
                 
                     
                     
                 
                     
                   DLWDWVVGKDEK, 
                   SEQ ID NO:80 
                 
                     
                     
                 
                     
                   DLWDWVVGEDEK, 
                   SEQ ID NO:81 
                 
                     
                     
                 
                     
                   DLWDWVKEEDEK, 
                   SEQ ID NO:82 
                 
                     
                     
                 
                     
                   TKRPDLIVDPIP, 
                   SEQ ID NO:98 
                 
                     
                     
                 
                     
                   DEVRPDLISTEE, 
                   SEQ ID NO:99 
                 
                     
                     
                 
                     
                   NLRPKYIXLDAD, 
                   SEQ ID NO:100 and 
                 
                     
                     
                 
                     
                   TLIAFADLVDVI. 
                   SEQ ID NO:101 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         7 . The peptide or polypeptide according to  claim 6 , which is modified to enhance stability or enhance adhesion molecule binding.  
     
     
         8 . The peptide or polypeptide according to  claim 6 , which is a multivalent peptide or polypeptide.  
     
     
         9 . A peptide or polypeptide consisting of from 7 to 15 amino acids, said peptide or polypeptide mimicking a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier, wherein said ligand is a Lewis SA-Le a  or SA-LeX antigen.  
     
     
         10 . The peptide or polypeptide according to  claim 9 , which is modified to enhance stability or enhance adhesion molecule binding.  
     
     
         11 . The peptide or polypeptide according to  claim 9 , which is a multivalent peptide or polypeptide.  
     
     
         12 . The peptide or polypeptide according to  claim 9 , which is selected form the group consisting of:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   DLWDFVVGKPAG, 
                   SEQ ID NO:63 
                     
                 
                     
                     
                 
                     
                   DLWDWVIGKPAG, 
                   SEQ ID NO:64 
                 
                     
                     
                 
                     
                   DLWDWVVAKPAG, 
                   SEQ ID NO:65 
                 
                     
                     
                 
                     
                   DLWDWVVSKPAG, 
                   SEQ ID NO:66 
                 
                     
                     
                 
                     
                   DLWDWVVEKPAG, 
                   SEQ ID NO:67 
                 
                     
                     
                 
                     
                   DLWDWVVDKPAG, 
                   SEQ ID NO:68 
                 
                     
                     
                 
                     
                   DLWDWVVGEPAG, 
                   SEQ ID NO:69 
                 
                     
                     
                 
                     
                   DLWDWVVGDPAG, 
                   SEQ ID NO:70 
                 
                     
                     
                 
                     
                   DLWDWVVGKEAG, 
                   SEQ ID NO:71 
                 
                     
                     
                 
                     
                   DLWDWVVGKDAG, 
                   SEQ ID NO:72 
                 
                     
                     
                 
                     
                   DLWDWVVGKPDG, 
                   SEQ ID NO:73 
                 
                     
                     
                 
                     
                   DLWDWVVGKPAD, 
                   SEQ ID NO:74 
                 
                     
                     
                 
                     
                   DLWDWVKEKPAG, 
                   SEQ ID NO:75 
                 
                     
                     
                 
                     
                   DLWDWVLAKPAG, 
                   SEQ ID NO:76 
                 
                     
                     
                 
                     
                   DLWDWVVGEDAG, 
                   SEQ ID NO:77 
                 
                     
                     
                 
                     
                   DLWDWVVGKPEK 
                   SEQ ID NO:78 
                 
                     
                     
                 
                     
                   DLWDWVKEEPAG, 
                   SEQ ID NO:79 
                 
                     
                     
                 
                     
                   DLWDWVVGKDEK, 
                   SEQ ID NO:80 
                 
                     
                     
                 
                     
                   DLWDWVVGEDEK, 
                   SEQ ID NO:81 
                 
                     
                     
                 
                     
                   DLWDWVKEEDEK, 
                   SEQ ID NO:82 
                 
                     
                     
                 
                     
                   TKRPDLIVDPIP, 
                   SEQ ID NO:98 
                 
                     
                     
                 
                     
                   DEVRPDLISTEE, 
                   SEQ ID NO:99 
                 
                     
                     
                 
                     
                   NLRPKYIXLDAD, 
                   SEQ ID NO:100 and 
                 
                     
                     
                 
                     
                   TLIAFADLVDVI. 
                   SEQ ID NO:101 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . A modified peptide or polypeptide mimicking a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier, wherein said ligand is a Lewis antigen and wherein said modification is selected from the group consisting of (i) use of one or more D amino acids, (ii) insertion of a moiety which can provide a net positive charge at the N-terminus of said peptide or polypeptide, (iii) insertion of a spacer of greater than 3 amino acids interposed between the N- and C-termini to cyclize the peptide, (iv) insertion of a free hydroxyl on the C-terminus, (v) insertion of an amide or imide on the C-terminus, and (vi) insertion of a sequence of one or up to about 15 additional amino acids on the C-terminus.  
     
     
         14 . The peptide or polypeptide according to  claim 13  which is modified by cyclizing the N- and C-termini.  
     
     
         15 . The peptide or polypeptide according to  claim 13 , wherein said modification enhances stability or enhance adhesion molecule binding.  
     
     
         16 . The peptide or polypeptide according to  claim 13 , which is a multivalent peptide or polypeptide.

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