US2012093913A1PendingUtilityA1

Inhibition of SYK kinase expression

Individually held — no corporate assignee on recordPriority: Jul 3, 2003Filed: May 3, 2011Published: Apr 19, 2012
Est. expiryJul 3, 2023(expired)· nominal 20-yr term from priority
A61P 37/02A61P 43/00A61P 7/04A61P 7/06A61P 29/00A61P 27/02A61P 13/10C12N 2310/14C12N 15/1137A61P 11/00C12Y 207/10001A61P 17/00
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Claims

Abstract

The present invention relates, in general, to Syk kinase and, in particular, to a method of inhibiting Syk kinase expression using small interfering RNA (siRNA).

Claims

exact text as granted — not AI-modified
1 . A method of inhibiting expression of Syk kinase in a cell comprising introducing into said cell small interfering RNA (siRNA) molecules that direct cleavage of a target Syk kinase mRNA sequence present in said cell thereby effecting said inhibition. 
     
     
         2 . The method according to  claim 1  wherein said siRNA molecules are about 20-23 nucleotides in length. 
     
     
         3 . The method according to  claim 1  wherein said siRNA molecules are introduced directly into said cell. 
     
     
         4 . The method according to  claim 1  wherein said siRNA molecules are produced intracellularly following introduction into said cell a nucleotide sequence encoding said siRNA molecule. 
     
     
         5 . The method according to  claim 1  wherein said siRNA molecules comprise two strands, and at least 1 strand of said siRNA molecules has a 3′ overhang of about 1 to about 6 nucleotides in length. 
     
     
         6 . The method according to  claim 5  wherein both strands of said siRNA molecules have 3′ overhangs of about 2 to 3 nucleotides in length. 
     
     
         7 . The method according to  claim 6  wherein said 3′ overhangs comprise uridines or thymidines. 
     
     
         8 . The method according to  claim 1  wherein said siRNA molecules have a stem loop structure. 
     
     
         9 . The method according to  claim 8  wherein the 3′ end of said stem loop structure has a 3′ overhang of about 1 to about 6 nucleotides in length. 
     
     
         10 . The method according to  claim 9  wherein said 3′ overhang is about 2 to about 3 nucleotides in length. 
     
     
         11 . The method according to  claim 1  wherein said target sequence is a sequence unique to Syk kinase mRNA. 
     
     
         12 . The method according to  claim 11  wherein said target sequence (expressed as the cDNA) comprises a nucleotide sequence selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   AATATGTGAAGCAGACATGGA, 
                 
                     
                 
                     
                   AATCAAATCATACTCCTTCCC, 
                 
                     
                 
                     
                   AAGAGAGTACTGTGTCATTCA, 
                 
                     
                 
                     
                   AAGGAAAACCTCATCAGGGAA, 
                 
                     
                 
                     
                   AATCATACTCCTTCCCAAAGC, 
                 
                     
                 
                     
                   AATTTTGGAGGCCGTCCACAA, 
                 
                     
                 
                     
                   AAGACTGGGCCCTTTGAGGAT, 
                 
                     
                 
                     
                   AAGCAGACATGGAACCTGCAG, 
                 
                     
                 
                     
                   AACTTCCAGGTTCCCATCCTG, 
                 
                     
                 
                     
                   AAGCCTGGCCACAGAAAGTCC, 
                 
                     
                 
                     
                   AAGCCCTACCCATGGACACAG, 
                 
                     
                 
                     
                   AACCTGCAGGGTCAGGCTCTG, 
                 
                     
                 
                     
                   AAGGGGTGCAGCCCAAGACTG, 
                 
                     
                 
                     
                   AACTTGCACCCTGGGCTGCAG, 
                 
                     
                 
                     
                   AAGTCCTCCCCTGCCCAAGGG, 
                 
                     
                 
                     
                   AAGGCCCCCAGAGAGAAGCCC, 
                 
                     
                 
                     
                   AATCTCAAGAATCAAATCATA, 
                 
                     
                 
                     
                   AATGTTAATTTTGGAGGCCGT, 
                 
                     
                 
                     
                   AATCCGTATGAGCCAGAACTT, 
                 
                     
                 
                     
                   AATCGGCACACAGGGAAATGT, 
                 
                     
                 
                     
                   AACCGGCAAGAGAGTACTGTG, 
                 
                     
                 
                     
                   AAGGAGGTTTACCTGGACCGA, 
                 
                     
                   and 
                 
                     
                 
                     
                   AACCTCATCAGGGAATATCTG. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . The method according to  claim 1  wherein said cell is a mammalian cell. 
     
     
         14 . The method according to  claim 13  wherein said cell is a human cell. 
     
     
         15 . The method according to  claim 14  wherein said cell is present in a human. 
     
     
         16 . The method according to  claim 15  wherein said human is a patient suffering from an inflammatory condition and said siRNA molecules are administered in an amount sufficient to effect treatment of said condition. 
     
     
         17 . The method according to  claim 16  wherein said inflammatory condition is a condition of the bronchi, lungs, eyes; bladder or skin of said patient. 
     
     
         18 . The method according to  claim 17  wherein said inflammatory condition is a condition of the bronchi or lungs and said siRNA molecules are introduced into bronchi or lung cells by inhalation. 
     
     
         19 . An siRNA molecule comprising a sequence complementary to a sequence selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   AATATGTGAAGCAGACATGGA, 
                 
                     
                 
                     
                   AATCAAATCATACTCCTTCCC, 
                 
                     
                 
                     
                   AAGAGAGTACTGTGTCATTCA, 
                 
                     
                 
                     
                   AAGGAAAACCTCATCAGGGAA, 
                 
                     
                 
                     
                   AATCATACTCCTTCCCAAAGC, 
                 
                     
                 
                     
                   AATTTTGGAGGCCGTCCACAA, 
                 
                     
                 
                     
                   AAGACTGGGCCCTTTGAGGAT, 
                 
                     
                 
                     
                   AAGCAGACATGGAACCTGCAG, 
                 
                     
                 
                     
                   AACTTCCAGGTTCCCATCCTG, 
                 
                     
                 
                     
                   AAGCCTGGCCACAGAAAGTCC, 
                 
                     
                 
                     
                   AAGCCCTACCCATGGACACAG, 
                 
                     
                 
                     
                   AACCTGCAGGGTCAGGCTCTG, 
                 
                     
                 
                     
                   AAGGGGTGCAGCCCAAGACTG, 
                 
                     
                 
                     
                   AACTTGCACCCTGGGCTGCAG, 
                 
                     
                 
                     
                   AAGTCCTCCCCTGCCCAAGGG, 
                 
                     
                 
                     
                   AAGGCCCCCAGAGAGAAGCCC, 
                 
                     
                 
                     
                   AATCTCAAGAATCAAATCATA, 
                 
                     
                 
                     
                   AATGTTAATTTTGGAGGCCGT, 
                 
                     
                 
                     
                   AATCCGTATGAGCCAGAACTT, 
                 
                     
                 
                     
                   AATCGGCACACAGGGAAATGT, 
                 
                     
                 
                     
                   AACCGGCAAGAGAGTACTGTG, 
                 
                     
                 
                     
                   AAGGAGGTTTACCTGGACCGA, 
                 
                     
                   and 
                 
                     
                 
                     
                   AACCTCATCAGGGAATATCTG. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         20 . A composition comprising the siRNA molecule according to  claim 19  and a carrier. 
     
     
         21 . A composition comprising the siRNA molecule according to  claim 19  and a liposome or polymer.

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