Details for Patent: 7,148,204

Title:	Antisense modulation of bcl-x expression
Abstract:	Compositions and methods are provided for modulating the expression of bcl-x. Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding bcl-x are preferred. Methods of using these compounds for modulation of bcl-x expression and for treatment of diseases associated with expression of bcl-x are also provided. Methods of sensitizing cells to apoptotic stimuli are also provided.
Inventor(s):	Bennett; C. Frank (Carlsbad, CA), Dean; Nicholas M. (Olivenhain, CA), Monia; Brett P. (Encinitas, CA), Nickoloff; Brian J. (Burr Ridge, IL), Zhang; Vivian Q. (San Diego, CA)
Assignee:	Isis Pharmaceuticala, Inc. (Carlsbad, CA)
Filing Date:	Nov 21, 2002
Application Number:	10/302,262
Claims:	1. An antisense compound 20 to 30 nucleobases in length targeted to nucleobases 876 through 895 or 907 through 926 of a 3' untranslated region of a nucleic acid molecule encoding a human bcl-x of SEQ ID NO: 1. 2. The antisense compound of claim 1 which is an antisense oligonucleotide. 3. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified intemucleoside linkage. 4. The antisense compound of claim 3 wherein the modified intemucleoside linkage of the antisense oligonucleotide is a phosphorothioate linkage, a morpholino linkage or a peptide-nucleic acid linkage. 5. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar moiety. 6. The antisense compound of claim 5 wherein the modified sugar moiety of the antisense oligonucleotide is a 2'-O-methoxyethyl sugar moiety or a 2'-dimethylaminooxyethoxy sugar moiety. 7. The antisense compound of claim 5 wherein more than one of the sugar moieties of the antisense oligonucleotide are modified sugar moieties. 8. The antisense compound of claim 3 wherein the antisense oligonucleotide comprises at least one modified nucleobase. 9. The antisense compound of claim 8 wherein the modified nucleobase of to antisense oligonucleotide is a 5-methylcytosine. 10. The antisense compound of claim 8 wherein each modified nucleobase of the antisense oligonucleotide is a 5-methylcytosine. 11. The antisense compound of claim 1 which is a chimeric oligonucleotide. 12. A pharmaceutical composition comprising the antisense compound of claim 1 and a pharmaceutically acceptable carrier or diluent. 13. The pharmaceutical composition of claim 12 further comprising a colloidal dispersion system. 14. The pharmaceutical composition of claim 12 wherein the antisense compound is an antisense oligonucleotide. 15. The antisense compound of claim 1 which is targeted to bcl-xl. 16. The pharmaceutical composition of claim 12 further comprising a chemotherapeutic agent for the treatment of cancer.