Antisense compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-2016138014-A1
Application number	US-201314435069-A
Country	US
Kind code	A1
Filing date	Oct 11, 2013
Priority date	Oct 12, 2012
Publication date	May 19, 2016
Grant date	—

Abstract

The present disclosure provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

First claim

What is claimed is:

1 .- 346 . (canceled)

347 . An oligomeric compound having the formula:
5′-X s —(X o ) n —(X s ) m -(d s ) q -(X o ) r —(X s ) p —(X)-3′
wherein each X independently comprises a modified nucleoside; each d comprises a 2′-deoxynucleoside; each subscript “s” comprises a phosphorothioate internucleoside linkage; each subscript “o” comprises a phosphodiester internucleoside linkage; n is an integer from 0 to 4; m is an integer from 0 to 4; q is an integer from 5 to 10; r is an integer from 0 to 4; and p is an integer from 0 to 5.

348 . The oligomeric compound of claim 347 , wherein m is 1.

349 . The oligomeric compound of claim 348 , wherein n is 1.

350 . The oligomeric compound of claim 348 , wherein n is 2.

351 . The oligomeric compound of claim 348 , wherein n is 3.

352 . The oligomeric compound of claim 348 , wherein r is 1.

353 . The oligomeric compound of claim 348 , wherein q is 5.

354 . The oligomeric compound of claim 348 , wherein q is 6.

355 . The oligomeric compound of claim 348 , wherein q is 7.

356 . The oligomeric compound of claim 348 , wherein q is 8.

357 . The oligomeric compound of claim 348 , wherein at least one modified nucleoside comprises a 2′-substituted sugar moiety comprising a 2′ substituent selected from among: halogen, optionally substituted allyl, optionally substituted amino, azido, optionally substituted SH, CN, OCN, CF 3 , OCF 3 , O, S, or N(R m )-alkyl; O, S, or N(R m )-alkenyl; O, S or N(R m )-alkynyl; optionally substituted O-alkylenyl-O-alkyl, optionally substituted alkynyl, optionally substituted alkaryl, optionally substituted aralkyl, optionally substituted O-alkaryl, optionally substituted O-aralkyl, O(CH 2 ) 2 SCH 3 , O—(CH 2 ) 2 —O—N(R m )(R n ) or O—CH 2 —C(═O)—N(R m )(R n ), where each R m and R n is, independently, H, an amino protecting group or substituted or unsubstituted C 1 -C 10 alkyl;
wherein each optionally substituted group is optionally substituted with a substituent group independently selected from among: hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro (NO 2 ), thiol, thioalkoxy(S-alkyl), halogen, alkyl, aryl, alkenyl and alkynyl.

358 . The oligomeric compound of claim 357 , wherein at least one modified nucleoside comprises a 2′-substituted sugar moiety comprising a 2′-substituent selected from among: a halogen, OCH 3 , OCF 3 , OCH 2 CH 3 , OCH 2 CF 3 , OCH 2 —CH═CH 2 , O(CH 2 ) 2 —OCH 3 , O(CH 2 ) 2 —O(CH 2 ) 2 —N(CH 3 ) 2 , OCH 2 C(═O)—N(H)CH 3 , OCH 2 C(═O)—N(H)—(CH 2 ) 2 —N(CH 3 ) 2 , and OCH 2 —N(H)—C(═NH)NH 2 .

359 . The oligomeric compound of claim 357 , wherein at least one modified nucleoside comprises a 2′-substituted sugar moiety comprising a 2′-substituent selected from among: F, OCH 3 , O(CH 2 ) 2 —OCH 3 .

360 . The oligomeric compound of claim 359 , wherein eight modified nucleosides comprises an O(CH 2 ) 2 —OCH 3 2′-substituent.

361 . The oligomeric compound of claim 359 , wherein nine modified nucleosides comprises an O(CH 2 ) 2 —OCH 3 2′-substituent.

362 . The oligomeric compound of claim 359 , wherein ten modified nucleosides comprises an O(CH 2 ) 2 —OCH 3 2′-substituent.

363 . The oligomeric compound of claim 348 , wherein each modified nucleoside comprises a 2′-substituted sugar moiety comprises an O(CH 2 ) 2 —OCH 3 2′-substituent.

364 . The oligomeric compound of claim 348 , wherein at least one modified nucleoside comprises a bicyclic sugar moiety selected from among: cEt, cMOE, LNA, α-LNA, ENA and 2′-thio LNA.

365 . The oligomeric compound of claim 348 , wherein at least two modified nucleosides comprises a bicyclic sugar moiety selected from among: cEt, cMOE, LNA, α-LNA, ENA and 2′-thio LNA.

366 . The oligomeric compound of claim 348 , wherein at least three modified nucleosides comprises a bicyclic sugar moiety selected from among: cEt, cMOE, LNA, α-LNA, ENA and 2′-thio LNA.

Assignees

• Isis Pharmaceuticals Inc

Inventors

• Kordasiewicz Holly
• Mazur Curt
• Seth Punit P
• Swayze Eric E

Classifications

• C12N2310/341

  Gapmers, i.e. of the type ===---=== · CPC title

• C12N2310/323

  modified ring structure · CPC title

• C12N2310/322

  2'-R Modification · CPC title

• C12N2320/53

  reducing unwanted side-effects · CPC title

• C12N2310/315

  Phosphorothioates · CPC title