Bispecific antisense olignucleotides that inhibit IGFBP-2 and IGFBP-5 and methods of using same

Abstract

Bispecific antisense oligonucleotides which consist essentially of a sequence of bases that is complementary to portions of both the gene encoding human IGFBP-2 and the gene encoding human IGFBP-5 are useful in as antisense therapeutics in the treatment of endocrine-regulated cancers.

1 . A bispecific antisense oligonucleotide which consist essentially of a sequence of bases that is complementary to portions of both the gene encoding IGFBP-2 and the gene encoding IGFBP-5, and which is sufficient length to act as an inhibitor of the effective amount of IGFBP-2 and IGFBP-5.  
     
     
         2 . The antisense oligonucleotide according to  claim 1 , wherein the oligonucleotide consists essentially of a series of bases as set forth in Seq. ID. No. 1.  
     
     
         3 . The antisense oligonucleotide according to  claim 1 , wherein the oligonucleotide consists essentially of a series of bases as set forth in Seq. ID. No. 2.  
     
     
         4 . The antisense oligonucleotide according to  claim 1 , wherein the oligonucleotide consists essentially of a series of bases as set forth in any of Seq. ID. Nos. 3 through 7.  
     
     
         5 . A method for making a pharmaceutical composition for treatment of endocrine-regulated cancers, comprising the steps of combining a bispecific antisense oligonucleotide with a pharmaceutically acceptable carrier for intravenous, intraperitoneal, subcutaneous or oral administration, wherein the bispecific antisense oligonucleotide consists essentially of a sequence of bases that is complementary to portions of both the gene encoding IGFBP-2 and the gene encoding IGFBP-5, and which is sufficient length to act as an inhibitor of the effective amount of IGFBP-2 and IGFBP-5.  
     
     
         6 . The method of  claim 5 , wherein the oligonucleotide consists essentially of a series of bases as set forth in Seq. ID. No. 1.  
     
     
         7 . The method of  claim 5 , wherein the oligonucleotide consists essentially of a series of bases as set forth in Seq. ID. No. 2.  
     
     
         8 . The method of  claim 5 , wherein the oligonucleotide consists essentially of a series of bases as set forth in any of Seq. ID. Nos. 3 through 7.  
     
     
         9 . A method for treating an endocrine-regulated cancer in a subject suffering from the endocrine-regulated cancer, comprising the step of administering to the subject a bispecific antisense oligonucleotide in an amount effective to reduce the effective levels of IGFBP-2 and/or IGFBP-5 in cells of the endocrine-regulated cancer, wherein the bispecific antisense oligonucleotide consists essentially of a sequence of bases that is complementary to portions of both the gene encoding IGFBP-2 and the gene encoding IGFBP-5, and which is sufficient length to act as an inhibitor of the effective amount of IGFBP-2 and IGFBP-5.  
     
     
         10 . The method of  claim 9 , wherein the oligonucleotide consists essentially of a series of bases as set forth in Seq. ID. No. 1.  
     
     
         11 . The method of  claim 9 , wherein the oligonucleotide consists essentially of a series of bases as set forth in Seq. ID. No. 2.  
     
     
         12 . The method of  claim 9 , wherein the oligonucleotide consists essentially of a series of bases as set forth in any of Seq. ID. Nos. 3 through 7.  
     
     
         13 . The method of  claim 9 , wherein the cancer is prostate cancer.  
     
     
         14 . The method of  claim 9 , wherein the cancer is breast cancer.  
     
     
         15 . A pharmaceutical composition comprising an antisense oligonucleotide and a pharmaceutically acceptable carrier, wherein the bispecific antisense oligonucleotide consists essentially of a sequence of bases that is complementary to portions of both the gene encoding IGFBP-2 and the gene encoding IGFBP-5, and which is sufficient length to act as an inhibitor of the effective amount of IGFBP-2 and IGFBP-5.  
     
     
         16 . The compositions of  claim 15 , wherein the oligonucleotide consists essentially of a series of bases as set forth in Seq. ID. No. 1.  
     
     
         17 . The compositions of  claim 15 , wherein the oligonucleotide consists essentially of a series of bases as set forth in Seq. ID. No. 2.  
     
     
         18 . The compositions of  claim 15 , wherein the oligonucleotide consists essentially of a series of bases as set forth in any of Seq. ID. Nos. 3 through 7.