Antisense modulation of PTP1B expression

Abstract

Compounds, compositions and methods are provided for modulating the expression of PTP1B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PTP1B. Methods of using these compounds for modulation of PTP1B expression and for treatment of diseases associated with expression of PTP1B are provided.

What is claimed is:  
     
         1 . A compound 8 to 50 nucleobases in length targeted to a nucleic acid molecule encoding PTP1B, wherein said compound specifically hybridizes with and inhibits the expression of PTP1B.  
     
     
         2 . The compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The compound of  claim 2  wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO: 18, 19, 20, 21, 22, 23, 24, 26, 27, 29, 30, 32, 33, 35, 36, 38, 39, 40, 42, 45, 46, 47, 48, 49, 50, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 69, 70, 72, 73, 75, 78, 79, 80, 81, 83, 84, 86, 87, 89, 90, 92, 93, 94, 95, 96, 97, 99, 100, 101, 102, 103, 104, 106, 107, 108, 109, 110, 112, 113, 114, 115, 117, 120, 121, 122, 123, 124, 126, 127, 128, 130, 131, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 144, 145, 146, 147, 148, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 168, 169, 170, 171, 172, 173, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 191, 193, 195, 196, 198, 201, 202, 204, 205, 206, 211, 215, 217, 219, 223, 225, 226, 228, 229, 230, 232, 233, 235, 236, 237, 239, 240, 244, 245, 247, 248, 249, 250, 251, 252, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 267, 268, 269, 271, 275, 276, 277, 278, 279, 281, 282, 283, 288, 290, 291, 292, 294, 296, 297, 298, 299, 300, 302, 303, 307, 310, 311, 313, 315, 317, 318, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 337, 340, 341, 342, 343, 344, 345, 347, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 360, 361, 362, 363, 364, 365, 366, 368, 369, 371, 372, 373, 374, 375, 377, 378, 380, 381, 384, 385, 386, 387, 388, or 389.  
     
     
         4 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         5 . The compound of  claim 4  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         6 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified sugar moiety.  
     
     
         7 . The compound of  claim 6  wherein the modified sugar moiety is a 2′-Q-methoxyethyl sugar moiety.  
     
     
         8 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified nucleobase.  
     
     
         9 . The compound of  claim 8  wherein the modified nucleobase is a 5-methylcytosine.  
     
     
         10 . The compound of  claim 2  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         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 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 PTP1B.  
     
     
         15 . A method of inhibiting the expression of PTP1B in cells or tissues comprising contacting said cells or tissues with the compound of  claim 1  so that expression of PTP1B is inhibited.  
     
     
         16 . The method of  claim 15  wherein the cells or tissues are human cells or tissues.  
     
     
         17 . The method of  claim 15  wherein the cells or tissues are rodent cells or tissues.  
     
     
         18 . The method of  claim 17  wherein the rodent cells or tissues are mouse cells or tissues.  
     
     
         19 . The method of  claim 17  wherein the rodent cells or tissues are rat cells or tissues.  
     
     
         20 . The method of  claim 15  wherein the cells or tissues are liver, kidney or adipose cells or tissues.  
     
     
         21 . A method of treating an animal having or suspected of having a disease or condition associated with PTP1B comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1  so that expression of PTP1B is inhibited.  
     
     
         22 . The method of  claim 21  wherein the animal is a human.  
     
     
         23 . The method of  claim 21  wherein the disease or condition is a metabolic disease or condition.  
     
     
         24 . The method of  claim 21  wherein the disease or condition is diabetes.  
     
     
         25 . The method of  claim 21  wherein the disease or condition is Type 2 diabetes.  
     
     
         26 . The method of  claim 21  wherein the disease or condition is obesity.  
     
     
         27 . The method of  claim 21  wherein the disease or condition is a hyperproliferative condition.  
     
     
         28 . The method of  claim 27  wherein the hyperproliferative condition is cancer.  
     
     
         29 . A method of decreasing blood glucose levels in an animal comprising administering to said animal the compound of  claim 1 .  
     
     
         30 . The method of  claim 29  wherein the animal is a human or a rodent.  
     
     
         31 . The method of  claim 29  wherein the blood glucose levels are plasma glucose levels or serum glucose levels.  
     
     
         32 . The method of  claim 29  wherein the animal is a diabetic animal.  
     
     
         33 . A method of preventing or delaying the onset of a disease or condition associated with PTP1B in an animal comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1 .  
     
     
         34 . The method of  claim 33  wherein the animal is a human.  
     
     
         35 . The method of  claim 33  wherein the disease or condition is a metabolic disease or condition.  
     
     
         36 . The method of  claim 33  wherein the disease or condition is diabetes.  
     
     
         37 . The method of  claim 33  wherein the disease or condition is Type 2 diabetes.  
     
     
         38 . The method of  claim 33  wherein the disease or condition is obesity.  
     
     
         39 . The method of  claim 33  wherein the disease or condition is a hyperproliferative condition.  
     
     
         40 . The method of  claim 39  wherein the hyperproliferative condition is cancer.  
     
     
         41 . A method of preventing or delaying the onset of an increase in blood glucose levels in an animal comprising administering to said animal the compound of  claim 1 .  
     
     
         42 . The method of  claim 41  wherein the animal is a human or a rodent.  
     
     
         43 . The method of  claim 41  wherein the blood glucose levels are plasma glucose levels or serum glucose levels.  
     
     
         44 . The method of  claim 41  wherein the animal is a diabetic animal.