Claims for Patent: 6,503,754

Summary for Patent: 6,503,754

Title:	Antisense modulation of BH3 interacting domain death agonist expression
Abstract:	Antisense compounds, compositions and methods are provided for modulating the expression of BH3 Interacting domain Death agonist. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding BH3 Interacting domain Death agonist. Methods of using these compounds for modulation of BH3 Interacting domain Death agonist expression and for treatment of diseases associated with expression of BH3 Interacting domain Death agonist are provided.
Inventor(s):	Zhang; Hong (Carlsbad, CA), Wyatt; Jacqueline (Encinitas, CA)
Assignee:	ISIS Pharmaceuticals, Inc. (Carlsbad, CA)
Application Number:	09/657,346
Patent Claims:	1. A compound 8 to 50 nucleobases in length targeted to nucleobases 354 through 373 or nucleobases 707 through 726 of a coding region of a nucleic acid molecule encoding human BH3 Interacting domain Death agonist of SEQ ID NO: 3, nucleobases 60 through 79 or nucleobases 2083 through 2102 of a 5'-untranslated region, nucleobases 2134 through 2153, nucleobases 8254 through 8273, nucleobases 8282 through 8306, nucleobases 8318 through 8332, nucleobases 8362 through 8381, nucleobases 8418 through 8437, nucleobases 12795 through 12830, nucleobases 12832 through 12851, nucleobases 12894 through 12913, nucleobases 14042 through 14061, nucleobases 14067 through 14091, nucleobases 14151 through 14170, nucleobases 14178 through 14217, or nucleobases 16678 through 16697 of a coding region, nucleobases 3582 through 3601, nucleobases 3845 through 3864, nucleobases 3906 through 3925, nucleobases 4540 through 4559, nucleobases 4580 through 4599, nucleobases 4987 through 5006, nucleobases 5092 through 5111, nucleobases 5373 through 5392, nucleobases 5778 through 5797, nucleobases 6999 through 7018, nucleobases 7125 through 7144, nucleobases 7369 through 7388, nucleobases 8083 through 8102, nucleobases 9135 through 9154, nucleobases 9353 through 9372, nucleobases 9424 through 9441, nucleobases 9797 through 9816, nucleobases 9875 through 9894, nucleobases 9992 through 10011, nucleobases 10172 through 10191, nucleobases 10643 through 10662, nucleobases 11311 through 11330, nucleobases 11394 through 11413, nucleobases 11641 through 11660, nucleobases 12649 through 12668, nucleobases 12734 through 12753, nucleobases 14635 through 14652, nucleobases 14694 through 14713, or nucleobases 16361 through 16380 of an intron region, or nucleobases 16753 through 16772, nucleobases 16798 through 16817, nucleobases 16933 through 16952, nucleobases 17176 through 17204, nucleobases 17236 through 17255, nucleobases 17267 through 17286, nucleobases 17293 through 17319, nucleobases 17391 through 17410, nucleobases 17415 through 17454, nucleobases 17439 through 17475, nucleobases 17588 through 17615, nucleobases 17632 through 17651, nucleobases 17731 through 17750, nucleobases 17757 through 17798, nucleobases 17802 through 17821, nucleobases 17904 through 17923, nucleobases 17942 through 17961, nucleobases 17966 through 17989 of a 3'-untranslated region of a nucleic acid molecule encoding human BH3 Interacting domain Death agonist of SEQ ID NO: 17, nucleobases 21 through 40 of a start codon region or nucleobases 232 through 251 of a coding region of a nucleic acid molecule encoding mouse BH3 Interacting domain Death agonist of SEQ ID NO: 10, nucleobases 4669 through 4688, nucleobases 4699 through 4718, nucleobases 5004 through 5023, nucleobases 5693 through 5712, nucleobases 6758 through 6777, nucleobases 7548 through 7567, nucleobases 7977 through 7996, nucleobases 8859 through 8878, nucleobases 9373 through 9392, nucleobases 9439 through 9458, nucleobases 9698 through 9717, nucleobases 9768 through 9785, nucleobases 10495 through 10514, nucleobases 11230 through 11249 nucleobases 12652 through 12671, nucleobases 14187 through 14206, nucleobases 14566 through 14585, nucleobases 17953 through 17972, nucleobases 18196 through 18215, nucleobases 19488 through 19507, nucleobases 19741 through 19771 of a 5'-untranslated region, nucleobases 19782 through 19801, nucleobases 21182 through 21201, nucleobases 21205 through 21224, nucleobases 21259 through 21278, nucleobases 21282 through 21301, nucleobases 21306 through 21325, nucleobases 24169 through 24187, nucleobases 24201 through 24227, nucleobases 24264 through 24283, nucleobases 25705 through 25724, nucleobases 25776 through 25795, nucleobases 25814 through 25877, or nucleobases 27236 through 27255 of a coding region, nucleobases 20989 through 21008, nucleobases 21013 through 21032, nucleobases 21950 through 21969, nucleobases 22293 through 22325, nucleobases 22835 through 22854, nucleobases 22883 through 22902, nucleobases 23125 through 23144, nucleobases 23239 through 23258, nucleobases 24515 through 24534, nucleobases 24877 through 24896, nucleobases 25363 through 25382, or nucleobases 26838 through 26857 of an intron region, or nucleobases 27315 through 27334, nucleobases 27474 through 27493, nucleobases 27577 through 27596, nucleobases 27608 through 27631, nucleobases 27657 through 27676, nucleobases 27700 through 27730, nucleobases 27788 through 27807, nucleobases 27834 through 27887, nucleobases 27934 through 27953, nucleobases 28042 through 28061, nucleobases 28067 through 28102, nucleobases 28107 through 28126, nucleobases 28245 through 28164, nucleobases 28167 through 28189, nucleobases 28192 through 28211, nucleobases 28332 through 28351, or nucleobases 28378 through 28397 of a 3'-untranslated region of a nucleic acid molecule encoding mouse BH3 Interacting domain Death agonist of SEQ ID NO: 96, wherein said compound specifically hybridizes with one of said regions and inhibits the expression of BH3 Interacting domain Death agonist. 2. The compound of claim 1 which is an antisense oligonucleotide. 3. A compound up to 50 nucleobases in length comprising at least an 8-nucleobase portion of SEQ ID NO: 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 52, 53, 54, 55, 56, 57, 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, 84, 85, 87, 88, 89, 90, 92, 94, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 123, 124, 125, 126, 128, 129, 130, 131, 132, 133, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173 or 174 which inhibits the expression of BH3 Interacting domain Death agonist. 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 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 BH3 Interacting domain Death agonist in cells or tissues comprising contacting said cells or tissues in vitro with the compound of claim 1 so that expression of BH3 Interacting domain Death agonist is inhibited. 15. The compound of claim 3 which is an antisense oligonucleotide. 16. The compound of claim 15 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage. 17. The compound of claim 16 wherein the modified internucleoside linkage is a phosphorothioate linkage. 18. The compound of claim 15 wherein the antisense oligonucleotide comprises at least one modified sugar moiety. 19. The compound of claim 18 wherein the modified sugar moiety is a 2'-O-methoxyethyl sugar moiety. 20. The compound of claim 15 wherein the antisense oligonucleotide comprises at least one modified nucleobase. 21. The compound of claim 20 wherein the modified nucleobase is a 5-methylcytosine. 22. The compound of claim 15 wherein the antisense oligonucleotide is a chimeric oligonucleotide. 23. A composition comprising the compound of claim 3 and a pharmaceutically acceptable carrier or diluent. 24. The composition of claim 23 further comprising a colloidal dispersion system. 25. The composition of claim 23 wherein the compound is an antisense oligonucleotide. 26. A method of inhibiting the expression of BH3 Interacting domain Death agonist in cells or tissues comprising contacting said cells or tissues in vitro with the compound of claim 3 so that expression of BH3 Interacting domain Death agonist is inhibited.

Details for Patent 6,503,754

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