IP Library Granted Patent US 7,875,733
Granted Patent B2
US 7,875,733 · App. 10/946,147 · Granted Jan 25, 2011

Oligomeric compounds comprising 4′-thionucleosides for use in gene modulation

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 7,875,733
App. No.
10/946,147
Granted
Jan 25, 2011
Kind
B2
Abstract

The present invention provides modified oligomeric compounds and compositions of oligomeric compounds for use in the RNA interference pathway of gene modulation. The modified oligomeric compounds include siRNA and asRNA having at least one affinity modification.

Claims (33)

1. A compound of formula (I):

wherein:

T 1 is H or a protecting group;

T 2 is a phosphoramidite group;

Bx is hydrogen or a nucleobase;

X is fluoro, substituted or unsubstituted —O—C 1 -C 12 alkyl, substituted or unsubstituted —O—C 2 -C 12 alkenyl, or substituted or unsubstituted —O—C 2 -C 12 alkynyl.

2. The compound of claim 1 , wherein X is a group of formula Ia:

wherein:

R b is O;

R d is a single bond, O, S or C(═O);

R e is C 1 -C 10 alkyl, N(R k )(R m ), N(R k )(R n ), N═C(R p )(R q ), N═C(R p )(R r ) or has formula Ic;

R p and R q are each independently hydrogen or C 1 -C 10 alkyl;

R r is —R x —R y ;

each R s , R t , R u and R v is, independently, hydrogen, C(O)R w , substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 2 -C 10 alkenyl, substituted or unsubstituted C 2 -C 10 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group or a conjugate group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;

or optionally, R u and R v , together form a phthalimido moiety with the nitrogen atom to which they are attached;

each R w is, independently, substituted or unsubstituted C 1 -C 10 alkyl, trifluoromethyl, cyanoethyloxy, methoxy, ethoxy, t-butoxy, allyloxy, 9-fluorenylmethoxy, 2-(trimethylsilyl)-ethoxy, 2,2,2-trichloroethoxy, benzyloxy, butyryl, iso-butyryl, phenyl or aryl;

R k is hydrogen, an amino protecting group or —R x —R y ;

R x is a bond or a linking moiety;

R y is a chemical functional group, a conjugate group or a solid support medium;

each R m and R n is, independently, H, an amino protecting group, substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 2 -C 10 alkenyl, substituted or unsubstituted C 2 -C 10 alkynyl, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl;

or R m and R n , together, are an amino protecting group, are joined in a ring structure that optionally includes an additional heteroatom selected from N and O or are a chemical functional group;

m a is 1 to about 10;

each mb is, independently, 0 or 1;

mc is 0 or an integer from 1 to 10;

m d is an integer from 1 to 10; and

provided that when mc is 0, and is greater than 1.

3. The compound of claim 1 , wherein X is selected from fluoro or substituted or unsubstituted —O—C 1 -C 12 alkyl.

4. The compound of claim 1 , wherein X is selected from fluoro, —O—CH 3 , or —O—CH 2 CH 2 —O—CH 3 .

5. The compound of claim 1 , wherein X is O-allyl, O—(CH 2 ) ma —O—N(R m )(R n ) or O—CH 2 —C(═O)—N(R m )(R n );

wherein:

each R m and R n is, independently, H, an amino protecting group, substituted or unsubstituted C 1 -C 10 alkyl, substituted or unsubstituted C 2 -C 10 alkenyl, substituted or unsubstituted C 2 -C 10 alkynyl; and

ma is from 1 to about 10.

6. The compound of claim 1 , wherein said phosphoramidite group is —P[N[(CH(CH 3 ) 2 ] 2 )O(CH 2 ) 2 CN.

Assignments (1)
CHANGE OF NAME Recorded Jul 26, 2017
From: ISIS PHARMACEUTICALS, INC.
To: IONIS PHARMACEUTICALS, INC.
Reel/Frame 043341/0420 →