Claims for Patent: 6,448,080

Summary for Patent: 6,448,080

Title:	Antisense modulation of WRN expression
Abstract:	Antisense compounds, compositions and methods are provided for modulating the expression of WRN. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding WRN. Methods of using these compounds for modulation of WRN expression and for treatment of diseases associated with expression of WRN are provided.
Inventor(s):	Ward; Donna T. (Murrieta, CA), Watt; Andrew T. (Vista, CA)
Assignee:	ISIS Pharmaceuticals, Inc. (Carlsbad, CA)
Application Number:	09/791,211
Patent Claims:	1. A compound 8 to 50 nucleobases in length targeted to nucleotides 37091 through 37110, nucleotides 38448 through 38467, nucleotides 54755 through 54774, nucleotides 55220 through 55239, nucleotides 81922 through 81941, nucleotides 94616 through 94635 (SEQ ID NO: 10), nucleotides 9993 through 10012, nucleotides 12240 through 12259, nucleotides 17702 through 17721, nucleotides 18784 through 18803, nucleotides 64718 through 64737 or SEQ ID NO: 10, or nucleotides 80767 through 80786 of an intron region (SEQ ID NO: 3), nucleotides 32 through 51 or nucleotides 174 through 193 of a 5'-untranslated region (SEQ ID NO: 11), nucleotides 222 through 241 of a start codon region (SEQ ID NO: 11), nucleotides 318 through 337, nucleotides 390 through 409, nucleotides 431 through 450, nucleotides 460 through 479, nucleotides 822 through 841, nucleotides 844 through 881, nucleotides 1249 through 1301, nucleotides 1427 through 1446, nucleotides 1491 through 1515, nucleotides 1572 through 1599, nucleotides 1653 through 1672, nucleotides 1684 through 1703, nucleotides 1847 through 1866, nucleotides 1874 through 1893, nucleotides 1938 through 1957, nucleotides 2051 through 2070, nucleotides 2153 through 2152, nucleotides 2221 through 2246, nucleotides 2495 through 2530, nucleotides 2665 through 2689, nucleotides 2696 through 2734, nucleotides 2769 through 2788, nucleotides 2852 through 2871, nucleotides 2954 through 2973, nucleotides 3016 through 3049, nucleotides 3181 through 3206, nucleotides 3225 through 3244, nucleotides 3265 through 3284, nucleotides 3455 through 3474, nucleotides 3531 through 3550, nucleotides 3681 through 3700, nucleotides 3830 through 3849, nucleotides 3877 through 3896, nucleotides 3930 through 3949, nucleotides 3999 through 4017, nucleotides 4234 through 4259, nucleotides 4274 through 4293, nucleotides 4519 through 4538, nucleotides 4240 through 4269, or nucleotides 4274 through 4293 of a coding region (SEQ ID NO: 11), nucleotides 4519 through 4538 of a stop codon region SEQ ID NO: 11), or nucleotides 4540 through 4559, nucleotides 4589 through 4624, nucleotides 4642 through 4661, nucleotides 4980 through 4999, nucleotides 5156 through 5175 (SEQ ID NO: 11), nucleotides 261 through 280, or nucleotides 299 through 318 of a 3'-untranslated region (SEQ ID NO: 12) of a nucleic acid molecule encoding human WRN, wherein said compound specifically hybridizes with one of said regions and inhibits the expression of human WRN. 2. The compound of claim 1 which is an antisense oligonucleotide. 3. A compound up to 30 nucleobases in length comprising at least a 8-nucleobase portion of SEQ ID NO: 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 28, 29, 30, 31, 33, 34, 35, 36, 38, 39, 40, 42, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 85, 86, 87, 89 or 90 which inhibits the expression of human WRN. 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'-O-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 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 WRN. 12. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or diluent. 13. The composition of claim 12 further comprising a colloidal dispersion system. 14. The composition of claim 12 wherein the compound is an antisense oligonucleotide. 15. A method of inhibiting the expression of human WRN in cells or tissues comprising contacting said cells or tissues in vitro with the compound of claim 1 so that expression of human WRN is inhibited. 16. The compound of claim 3 which is an antisense oligonucleotide. 17. The compound of claim 16 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage. 18. The compound of claim 17 wherein the modified internucleoside linkage is a phosphorothioate linkage. 19. The compound of claim 16 wherein the antisense oligonucleotide comprises at least one modified sugar moiety. 20. The compound of claim 19 wherein the modified sugar moiety is a 2'-O-methoxyethyl sugar moiety. 21. The compound of claim 16 wherein the antisense oligonucleotide comprises at least one modified nucleobase. 22. The compound of claim 21 wherein the modified nucleobase is a 5-methylcytosine. 23. The compound of claim 16 wherein the antisense oligonucleotide is a chimeric oligonucleotide. 24. A composition comprising the compound of claim 3 and a pharmaceutically acceptable carrier or diluent. 25. The composition of claim 24 further comprising a colloidal dispersion system. 26. The composition of claim 24 wherein the compound is an antisense oligonucleotide. 27. A method of inhibiting the expression of human WRN in human cells or tissues comprising contacting said cells or tissues in vitro with the compound of claim 3 so that expression of human WRN is inhibited.

Details for Patent 6,448,080

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2039-02-26
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2039-02-26
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2039-02-26