US5386023A
Expired / Lapsed
US
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Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
Assignee: Ionis Pharmaceuticals Inc
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Filing: 1993-03-31
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Granted: 1995-01-31
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Expires: 2013-03-31
Abstract
Abstract Methods for preparing oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. In preferred embodiments, the methods involve reductive coupling of 3'- and 4'-substituted or 4'- and 3'-substituted nucleosidic synthons.
Inventors
- 👤 Yogesh S. Sanghvi
- 👤 Phillip D. Cook
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 06:47
CPC Classifications
C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/06; A; A61; A61K; A61K31/00; A61K31/70; A61K47/00; A61K47/50; A61K47/51; A61K47/54; A61K47/549; C07D; C07D405/00; C07D405/02; C07D405/04; C07D405/14; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/18; C07F7/1804; C07H19/10; C07H19/16; C07H21/00
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
171 words
A method for forming between adjacent sugar moieties a covalent linkage having structure CH═N--R A --CH 2 , CH 2 --R A --N═CH, or R A --N═CH--CH 2 where R A is O or NR 1 , comprising the steps of: (a) providing synthons having structure: ##STR4## (b) contacting said synthons for a time and under reaction conditions effective to form said covalent linkage; wherein: Z 1 and Y 2 are selected such that (i) Z 1 is C(O)H and Y 2 is CH 2 R A NH 2 ; or (ii) Z 1 is CH 2 R A NH 2 and Y 2 is C(O)H; or (iii) Z 1 is R A NH 2 and Y 2 is H(O)CCH 2 ; R 1 is H or alkyl having 1 to about 10 carbon atoms; B X1 and B X2 are, independently, nucleosidic bases; Q 1 and Q 2 are O; and X 1 and X 2 are, independently, H; OH; F; or O-alkyl having 1 to about 10 carbon atoms.
Claim 2
Independent Claim
171 words
A method for forming between adjacent sugar moieties a covalent linkage having structure CH═N--R A --CH 2 , CH 2 --R A --N═CH, or R A --N═CH--CH 2 where R A is O or NR 1 , comprising the steps of: (a) providing synthons having structure: ##STR4## (b) contacting said synthons for a time and under reaction conditions effective to form said covalent linkage; wherein: Z 1 and Y 2 are selected such that (i) Z 1 is C(O)H and Y 2 is CH 2 R A NH 2 ; or (ii) Z 1 is CH 2 R A NH 2 and Y 2 is C(O)H; or (iii) Z 1 is R A NH 2 and Y 2 is H(O)CCH 2 ; R 1 is H or alkyl having 1 to about 10 carbon atoms; B X1 and B X2 are, independently, nucleosidic bases; Q 1 and Q 2 are O; and X 1 and X 2 are, independently, H; OH; F; or O-alkyl having 1 to about 10 carbon atoms.
Claim 3
Dependent Claim
10 words
The method of claim 1 wherein R A is O.
Claim 4
Dependent Claim
14 words
The method of claim 1 wherein R A is NH or NCH 3 .
Claim 5
Dependent Claim
21 words
The method of claim 1 wherein Z 1 is C(O)H and Y 2 is CH 2 R A NH 2 .
Claim 6
Dependent Claim
20 words
The method of claim 1 wherein Z 1 is CH 2 R A NH 2 and Y 2 is C(O)H.
Claim 7
Dependent Claim
20 words
The method of claim 1 wherein Z 1 is R A NH 2 and Y 2 is H(O)CCH 2 .
Claim 8
Dependent Claim
17 words
The method of claim 1 wherein at least one of X 1 and X 2 is H.
Claim 9
Dependent Claim
17 words
The method of claim 1 wherein at least one of X 1 and X 2 is OH.
Claim 10
Dependent Claim
17 words
The method of claim 1 wherein at least one of X 1 and X 2 is F.
Claim 11
Dependent Claim
17 words
The method of claim 1 wherein at least one of X 1 and X 2 is O-alkyl.
Claim 12
Independent Claim
197 words
A method for forming between adjacent sugar moieties a covalent linkage having structure CH 2 --NR 1 --R A --CH 2 , CH 2 --R A --NR 1 --CH 2 , R A --NR 1 --CH 2 --CH 2 where R A is O or NR 2 , comprising the steps of: (a) providing synthons having structures: ##STR5## (b) contacting said synthons for a time and under reaction conditions effective to form an intermediate linkage; and (c) reducing said intermediate linkage to form said covalent linkage; wherein: Z 1 and Y 2 are selected such that (i) Z 1 is C(O)H and Y 2 is CH 2 R A NH 2 ; or (ii) Z 1 is CH 2 R A NH 2 and Y 2 is C(O)H; or (iii) Z 1 is R A NH 2 and Y 2 is H(O)CCH 2 ; R 1 and R 2 are, independently, H or alkyl having 1 to about 10 carbon atoms; B X1 and B X2 are, independently, nucleosidic bases; Q 1 and Q 2 are O; and X 1 and X 2 are, independently, H; OH; F; or O-alkyl having 1 to about 10 carbon atoms.
Claim 13
Independent Claim
197 words
A method for forming between adjacent sugar moieties a covalent linkage having structure CH 2 --NR 1 --R A --CH 2 , CH 2 --R A --NR 1 --CH 2 , R A --NR 1 --CH 2 --CH 2 where R A is O or NR 2 , comprising the steps of: (a) providing synthons having structures: ##STR5## (b) contacting said synthons for a time and under reaction conditions effective to form an intermediate linkage; and (c) reducing said intermediate linkage to form said covalent linkage; wherein: Z 1 and Y 2 are selected such that (i) Z 1 is C(O)H and Y 2 is CH 2 R A NH 2 ; or (ii) Z 1 is CH 2 R A NH 2 and Y 2 is C(O)H; or (iii) Z 1 is R A NH 2 and Y 2 is H(O)CCH 2 ; R 1 and R 2 are, independently, H or alkyl having 1 to about 10 carbon atoms; B X1 and B X2 are, independently, nucleosidic bases; Q 1 and Q 2 are O; and X 1 and X 2 are, independently, H; OH; F; or O-alkyl having 1 to about 10 carbon atoms.
Claim 14
Dependent Claim
10 words
The method of claim 11 wherein R A is O.
Claim 15
Dependent Claim
14 words
The method of claim 11 wherein R A is NH or NCH 3 .
Claim 16
Dependent Claim
21 words
The method of claim 11 wherein Z 1 is C(O)H and Y 2 is CH 2 R A NH 2 .
Claim 17
Dependent Claim
20 words
The method of claim 11 wherein Z 1 is CH 2 R A NH 2 and Y 2 is C(O)H.
Claim 18
Dependent Claim
20 words
The method of claim 11 wherein Z 1 is R A NH 2 and Y 2 is H(O)CCH 2 .
Claim 19
Dependent Claim
17 words
The method of claim 11 wherein at least one of X 1 and X 2 is H.
Claim 20
Dependent Claim
17 words
The method of claim 11 wherein at least one of X 1 and X 2 is OH.
Claim 21
Dependent Claim
17 words
The method of claim 11 wherein at least one of X 1 and X 2 is F.
Claim 22
Dependent Claim
17 words
The method of claim 11 wherein at least one of X 1 and X 2 is O-alkyl.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1998-01-30 | 1998-08-01 | 1999-01-31 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2002-01-30 | 2002-08-01 | 2003-01-31 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2006-01-30 | 2006-08-01 | 2007-01-31 | $7700.00 | Window Closed / Lapsed |