Patent US5677437A successfully refreshed from Google Patents.
US5677437A
Expired / Lapsed
US
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Heteroatomic oligonucleoside linkages
Assignee: Ionis Pharmaceuticals Inc
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Filing: 1995-02-23
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Granted: 1997-10-14
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Expires: 2015-02-23
Abstract
Abstract Oligonucleotide-mimicking macromolecules that have improved nuclease resistance are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligonucleotides with four atom linking groups provide unique compounds that are useful in regulating RNA expression and in therapeutics. Methods of synthesis and use also are disclosed.
Inventors
- 👤 Kelly Teng
- 👤 Yogesh S. Sanghvi
- 👤 Phillip Dan Cook
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 01:28
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; C; C07; C07D; C07D405/00; C07D405/02; C07D405/04; C07D405/14; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/18; C07F7/1804; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/06; C07H19/10; C07H19/16; C07H21/00
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
463 words
A compound having structure: ##STR7## wherein: L 1 --L 2 --L 3 --L 4 is CR 1a R 1b --CR 2a R 2b --CR 3a R 3b --Z 4 , CR 1a R 1a --CR 2a R 2b --Z 3 --Z 4 , CR 1a R 1b --Z 2 --CR 3a R 3b --Z 4 , Z 1 --CR 2a R 2b --CR 3a R 3b --Z 4 , CR 1a R 1b --Z 2 --Z 3 --Z 4 , Z 1 --CR 2a R 2b --Z 3 --Z 4 or Z 1 --Z 2 --CR 3a R 3b --Z 4 ; Z 1 , Z 2 , Z 3 and Z 4 are, independently, O, NR 4 , S, SO, SO 2 , Se, P(═Y 1 )Y 2 or Si(R 6 ) 2 ; R 1a , R 1b , R 2a , R 2b , R 3a and R 3b are, independently, H, R 5 , O--R 5 , S--R 5 , NR 4 R 5 ; or, independently, together R 1a and R 1b , or R 2a and R 2b , or R 3a and R 3b are ═O; X is H, OH, O--R 5 , S--R 5 , NR 4 --R 5 , R 5 , F, Cl, Br, CN, CF 3 , OCF 3 , OCN, SOCH 3 , SO 2 CH 3 , ONO 2 , NO 2 , N 3 , aminoalkylamino, polyalkylamino or substituted silyl; Y 1 is O, S, Se, or NR 4 ; Y 2 is OH, OR 5 , SH, SR 5 , SeH, R 5 , BH 3 or NR 4 R 5 ; R 4 , R 5 and R 6 are, independently, one of: an electron pair of a multiple bond; H; straight or branched chain alkyl or substituted alkyl; straight or branched chain alkenyl or substituted alkenyl; straight or branched chain alkynyl or substituted alkynyl; 14 C-containing lower alkyl, lower alkenyl or lower alkynyl; substituted or unsubstituted alkaryl or aralkyl; 14 C-containing alkaryl or aralkyl; aryl; alicyclic; a reporter molecule; and where said substituents are OH, ═O, CO 2 H, O-alkyl, SH, S-alkyl, NH-alkyl, N-(alkyl) 2 , alkyl, F, Cl, Br, CN, CF 3 , OCF 3 , OCN, SOCH 3 , SO 2 CH 3 , ONO 2 , NO 2 , N 3 , NH 2 , aryl, aralkyl, sulfide, or silyl; Q is O or CH 2 ; n is an integer greater than 0; Bx is a variable heterocyclic base moiety; and said alkyl groups have 1 to 12 carbon atoms, said alkenyl and alkynyl groups have 2 to 12 carbon atoms, said alkaryl and aralkyl groups have 7 to 14 carbon atoms, and said aryl groups have 6 to 14 carbon atoms.
Claim 2
Dependent Claim
463 words
A compound having structure: ##STR7## wherein: L 1 --L 2 --L 3 --L 4 is CR 1a R 1b --CR 2a R 2b --CR 3a R 3b --Z 4 , CR 1a R 1a --CR 2a R 2b --Z 3 --Z 4 , CR 1a R 1b --Z 2 --CR 3a R 3b --Z 4 , Z 1 --CR 2a R 2b --CR 3a R 3b --Z 4 , CR 1a R 1b --Z 2 --Z 3 --Z 4 , Z 1 --CR 2a R 2b --Z 3 --Z 4 or Z 1 --Z 2 --CR 3a R 3b --Z 4 ; Z 1 , Z 2 , Z 3 and Z 4 are, independently, O, NR 4 , S, SO, SO 2 , Se, P(═Y 1 )Y 2 or Si(R 6 ) 2 ; R 1a , R 1b , R 2a , R 2b , R 3a and R 3b are, independently, H, R 5 , O--R 5 , S--R 5 , NR 4 R 5 ; or, independently, together R 1a and R 1b , or R 2a and R 2b , or R 3a and R 3b are ═O; X is H, OH, O--R 5 , S--R 5 , NR 4 --R 5 , R 5 , F, Cl, Br, CN, CF 3 , OCF 3 , OCN, SOCH 3 , SO 2 CH 3 , ONO 2 , NO 2 , N 3 , aminoalkylamino, polyalkylamino or substituted silyl; Y 1 is O, S, Se, or NR 4 ; Y 2 is OH, OR 5 , SH, SR 5 , SeH, R 5 , BH 3 or NR 4 R 5 ; R 4 , R 5 and R 6 are, independently, one of: an electron pair of a multiple bond; H; straight or branched chain alkyl or substituted alkyl; straight or branched chain alkenyl or substituted alkenyl; straight or branched chain alkynyl or substituted alkynyl; 14 C-containing lower alkyl, lower alkenyl or lower alkynyl; substituted or unsubstituted alkaryl or aralkyl; 14 C-containing alkaryl or aralkyl; aryl; alicyclic; a reporter molecule; and where said substituents are OH, ═O, CO 2 H, O-alkyl, SH, S-alkyl, NH-alkyl, N-(alkyl) 2 , alkyl, F, Cl, Br, CN, CF 3 , OCF 3 , OCN, SOCH 3 , SO 2 CH 3 , ONO 2 , NO 2 , N 3 , NH 2 , aryl, aralkyl, sulfide, or silyl; Q is O or CH 2 ; n is an integer greater than 0; Bx is a variable heterocyclic base moiety; and said alkyl groups have 1 to 12 carbon atoms, said alkenyl and alkynyl groups have 2 to 12 carbon atoms, said alkaryl and aralkyl groups have 7 to 14 carbon atoms, and said aryl groups have 6 to 14 carbon atoms.
Claim 3
Dependent Claim
30 words
The compound of claim 1 wherein L 1 --L 2 --L 3 --L 4 is CR 1a R 1b --CR 2a R 2b --CR 3a R 3b --Z 4 .
Claim 4
Dependent Claim
28 words
The compound of claim 1 wherein L 1 --L 2 --L 3 --L 4 is CR 1a R 1a --CR 2a R 2b --Z 3 --Z 4 .
Claim 5
Dependent Claim
28 words
The compound of claim 1 wherein L 1 --L 2 --L 3 --L 4 is CR 1a R 1b --Z 2 --CR 3a R 3b --Z 4 .
Claim 6
Dependent Claim
28 words
The compound of claim 1 wherein L 1 --L 2 --L 3 --L 4 is Z 1 --CR 2a R 2b --CR 3a R 3b --Z 4 .
Claim 7
Dependent Claim
26 words
The compound of claim 1 wherein L 1 --L 2 --L 3 --L 4 is CR 1a R 1b --Z 2 --Z 3 --Z 4 .
Claim 8
Dependent Claim
26 words
The compound of claim 1 wherein L 1 --L 2 --L 3 --L 4 is Z 1 --Z 2 --CR 3a R 3b --Z 4 .
Claim 9
Dependent Claim
26 words
The compound of claim 1 wherein L 1 --L 2 --L 3 --L 4 is Z 1 --CR 2a R 2b --Z 3 --Z 4 .
Claim 10
Dependent Claim
9 words
The compound of claim 1 wherein Q is O.
Claim 11
Dependent Claim
11 words
The compound of claim 1 wherein X is H or OH.
Claim 12
Dependent Claim
18 words
The compound of claim 1 R 4 is H or straight or branched chain alkyl or substituted alkyl.
Claim 13
Dependent Claim
15 words
The compound of claim 2 wherein Z 4 is O, S or NR 4 .
Claim 14
Dependent Claim
19 words
The compound of claim 3 wherein Z 3 and Z 4 are, independently, O, S or NR 4 .
Claim 15
Dependent Claim
19 words
The compound of claim 5 wherein Z 1 and Z 4 are, independently, O, S or NR 4 .
Claim 16
Dependent Claim
27 words
The compound of claim 14 wherein Z 1 and Z 4 are O; and R 2a , R 2b , R 3a and R 3b are H.
Claim 17
Dependent Claim
19 words
The compound of claim 4 wherein Z 2 and Z 4 are, independently, O, S or NR 4 .
Claim 18
Dependent Claim
22 words
The compound of claim 6 wherein Z 2 , Z 3 and Z 4 are, independently, O, S or NR 4 .
Claim 19
Dependent Claim
22 words
The compound of claim 7 wherein Z 1 , Z 2 and Z 4 are, independently, O, S or NR 4 .
Claim 20
Dependent Claim
22 words
The compound of claim 8 wherein Z 1 , Z 3 and Z 4 are, independently, O, S or NR 4 .
Claim 21
Dependent Claim
25 words
The compound of claim 1 wherein Z 1 , Z 2 , Z 3 and Z 4 are, independently, O, S or NR 4 .
Claim 22
Dependent Claim
51 words
The compound of claim 1 wherein Z 4 is O, S or NR 4 ; one of Z 1 , Z 2 or Z 3 is P(═Y 1 )Y 2 and the others of Z 1 , Z 2 or Z 3 are O, S, NR 4 or CH 2 .
Claim 23
Dependent Claim
22 words
The compound of claim 21 wherein Z 1 is O, S, NR 4 or CH 2 ; and Z 4 is O.
Claim 24
Dependent Claim
13 words
The compound of claim 22 wherein Z, is O or CH 2 .
Claim 25
Dependent Claim
43 words
The compound of claim 1 wherein R 5 is straight or branched chain lower alkyl or substituted lower alkyl; straight or branched chain lower alkenyl or substituted lower alkenyl; straight or branched chain lower alkynyl or substituted lower alkynyl; or alkaryl or aralkyl.
Claim 26
Dependent Claim
25 words
The compound of claim 1 wherein R 4 and R 5 are, independently, H or straight or branched chain lower alkyl or substituted lower alkyl.
Claim 27
Dependent Claim
33 words
The compound of claim 1 wherein R 4 and R 5 are an electron pair such that one of L 1 --L 2 or L 2 --L 3 together is an alkene moiety.
Claim 28
Dependent Claim
10 words
The compound of claim 1 wherein Z 4 is O.
Claim 29
Dependent Claim
23 words
The compound of claim 27 wherein one of Z 2 or Z 3 is SO, SO 2 or Si(R 6 ) 2 .
Claim 30
Dependent Claim
18 words
The compound of claim 1 wherein R 6 is straight or branched chain lower alkyl, aralkyl or aryl.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-10-13 | 2001-04-14 | 2001-10-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-10-13 | 2005-04-14 | 2005-10-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-10-13 | 2009-04-14 | 2009-10-14 | $7700.00 | Window Closed / Lapsed |