Oligonucleotide modulation of her-1 expression

Abstract

Compounds, compositions and methods are provided for inhibiting the expressionof human Her-1. The compositions comprise oligonucleotides complementary to mRNA targeted to nucleic acids encoding Her-1. Methods of using these oligonucleotides for inhibition of Her-1 expression and for treatment of diseases such as cancers associated with overexpression of Her-1 are provided.

What is claimed is:  
     
         1 . A compound 8 to 50 nucleobases in length targeted to a nucleic acid molecule encoding epidermal growth factor receptor and comprising at least an 8 nucleobase portion of SEQ ID NO 27, 28, 29, 30, 31, 32, 33, 36, 37, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 57, 59, 60, 61, 62, 63, 64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 99, 100, 101, 102, 103, 105, 106, 107, 108, 109, 110, 111, 112, 114, 116, 117, 118, 119, 120, 121, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 147, 148, 149, 150, 152, 154, 155, 156, 158, 159, 161, 162, 163, 164, 165, 166, 167, 168, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181 or 182, wherein said oligonucleotide inhibits the expression of said human epidermal growth factor receptor.  
     
     
         2 . The compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         4 . The compound of  claim 3  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         5 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified sugar moiety.  
     
     
         6 . The compound of  claim 5  wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.  
     
     
         7 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified nucleobase.  
     
     
         8 . The compound of  claim 7  wherein the modified nucleobase is a 5-methylcytosine.  
     
     
         9 . The compound of  claim 2  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         10 . A compound 8 to 50 nucleobases in length which specifically hybridizes with at least an 8-nucleobase portion of an active site on a nucleic acid molecule encoding epidermal growth factor receptor.  
     
     
         11 . A composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         12 . The composition of  claim 11  further comprising a colloidal dispersion system.  
     
     
         13 . The composition of  claim 11  wherein the compound is an antisense oligonucleotide.  
     
     
         14 . A method of inhibiting the expression of epidermal growth factor receptor in cells or tissues comprising contacting said cells or tissues with the compound of  claim 1  so that expression of epidermal growth factor receptor is inhibited.  
     
     
         15 . A method of treating an animal having a disease or condition associated with epidermal growth factor receptor comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1  so that expression of epidermal growth factor receptor is inhibited.  
     
     
         16 . The method of  claim 15  wherein the disease or condition is a hyperproliferative disease or condition.  
     
     
         17 . The method of  claim 16  wherein the hyperproliferative disease or condition is cancer.  
     
     
         18 . The method of  claim 17  wherein the cancer is lung cancer, ovarian cancer, colon cancer or prostate cancer.  
     
     
         19 . The method of  claim 16  wherein the hyperproliferative disease or condition is psoriasis.