US2008026947A1PendingUtilityA1

Cytotoxic nucleotides for targeted therapeutics

55
Individually held — no corporate assignee on recordPriority: Feb 8, 2006Filed: Feb 8, 2007Published: Jan 31, 2008
Est. expiryFeb 8, 2026(expired)· nominal 20-yr term from priority
Inventors:William H. Gmeiner
C40B 20/04C40B 20/06
55
PatentIndex Score
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Claims

Abstract

The present invention provides a method of generating a nucleic acid, which specifically binds to an extracellular surface protein expressed by a cell of interest, and which nucleic acid comprises a compound of interest to be delivered to the cell of interest.

Claims

exact text as granted — not AI-modified
1 . A method of generating a nucleic acid of interest, which nucleic acid specifically binds to an extracellular surface protein expressed by a cell of interest, and which nucleic acid is capable of being internalized by said cell of interest, said method comprising the steps of: 
 combining a first pool comprising different nucleic acids with said extracellular surface protein;    selecting a first subpopulation of nucleic acids from said first pool, said first subpopulation comprising at least one nucleic acid that specifically binds to said extracellular surface protein;    amplifying said at least one nucleic acid of said first subpopulation; and    selecting a second subpopulation comprising at least one nucleic acid species from said first subpopulation which is internalized by said cell of interest.    
     
     
         2 . The method of  claim 1 , wherein said cell of interest is a cancer cell.  
     
     
         3 . The method of  claim 1 , wherein said cell of interest is a microbial cell.  
     
     
         4 . The method of  claim 1 , wherein said cell of interest is a parasitic cell.  
     
     
         5 . The method of  claim 1 , wherein said nucleic acid comprises a compound of interest.  
     
     
         6 . The method of  claim 5 , wherein said compound of interest is an active compound.  
     
     
         7 . The method of  claim 5 , wherein said compound of interest is a detectable group.  
     
     
         8 . The method of  claim 5 , where said nucleic acid comprises more than one compound of interest.  
     
     
         9 . The method of  claim 6 , wherein said active compound comprises cytotoxic nucleotides.  
     
     
         10 . The method of  claim 9 , wherein said cytotoxic nucleotides comprise poly-FdUMP.  
     
     
         11 . The method of  claim 10 , wherein said poly-FdUMP comprises FdUMP[9] or FdUMP[10].  
     
     
         12 . The method of  claim 1 , wherein said amplifying step further comprises sequencing at least one selected nucleic acid from said first subpopulation.  
     
     
         13 . The method of  claim 1 , further comprising the step of synthesizing a synthetic nucleic acid having a sequence corresponding to said selected nucleic acid, and further comprising a compound of interest.  
     
     
         14 . The method of  claim 1 , wherein said extracellular surface protein is an extracellular surface protein differentially expressed by cancer cells.  
     
     
         15 . The method of  claim 14 , wherein said extracellular surface protein comprises an extracellular surface portion of prostate specific membrane antigen (PSMA).  
     
     
         16 . The method of  claim 1 , wherein said first pool comprises nucleic acids having a predetermined bias.  
     
     
         17 . A method of generating a nucleic acid of interest, which nucleic acid specifically binds to an extracellular surface protein expressed by a cell of interest, which nucleic acid is capable of being internalized by said cell of interest, and which nucleic acid comprises one or more compounds of interest to be delivered to said cell of interest, said method comprising the steps of: 
 combining a first pool comprising different nucleic acids with said extracellular surface protein;    selecting a first subpopulation of nucleic acids from said first pool, said first subpopulation comprising at least one nucleic acid that specifically binds to said extracellular surface protein;    amplifying said at least one nucleic acid of said first subpopulation;    selecting a second subpopulation comprising at least one nucleic acid species from said first subpopulation which is internalized by said cell of interest;    determining a first chemical structure of a nucleic acid from said second population;    determining a second chemical structure of a nucleic acid which is an analog of said nucleic acid from said second population, said analog comprising one or more of said compounds of interest;    analyzing the folding properties of said first chemical structure;    analyzing the folding properties of said second chemical structure;    comparing the folding properties of said first chemical structure with that of said second chemical structure; and    generating a nucleic acid of interest based upon said comparing.    
     
     
         18 . The method of  claim 17 , wherein said cell of interest is a cancer cell.  
     
     
         19 . The method of  claim 17 , wherein said cell of interest is a microbial cell.  
     
     
         20 . The method of  claim 17 , wherein said cell of interest is a parasitic cell.  
     
     
         21 . The method of  claim 17 , wherein said compound of interest is an active compound.  
     
     
         22 . The method of  claim 17 , wherein said compound of interest is a detectable group.  
     
     
         23 . The method of  claim 17 , where said nucleic acid of interest comprises more than one compound of interest.  
     
     
         24 . The method of  claim 21 , wherein said active compound comprises cytotoxic nucleotides.  
     
     
         25 . The method of  claim 24 , wherein said cytotoxic nucleotides comprise poly-FdUMP.  
     
     
         26 . The method of  claim 25 , wherein said poly-FdUMP comprises FdUMP[9] or FdUMP[10].  
     
     
         27 . The method of  claim 17 , wherein said amplifying step further comprises sequencing at least one selected nucleic acid from said first subpopulation.  
     
     
         28 . The method of  claim 17 , wherein said determining a first chemical structure comprises sequencing said at least one selected nucleic acid from said second subpopulation.  
     
     
         29 . The method of  claim 17 , wherein said generating step comprises synthesizing a synthetic nucleic acid having a sequence corresponding to said selected nucleic acid of interest.  
     
     
         30 . The method of  claim 17 , wherein said extracellular surface protein is an extracellular surface protein differentially expressed by cancer cells.  
     
     
         31 . The method of  claim 30 , wherein said extracellular surface protein comprises an extracellular surface portion of prostate specific membrane antigen (PSMA).  
     
     
         32 . The method of  claim 17 , wherein said first pool comprises nucleic acids having a predetermined bias.

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