US6172216B1
Expired / Lapsed
US
⏱️ 0.0 years remaining
Antisense modulation of BCL-X expression
Assignee: Ionis Pharmaceuticals Inc
•
Filing: 1998-10-07
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Granted: 2001-01-09
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Expires: 2018-10-07
Abstract
Abstract Compositions and methods are provided for modulating the expression of bcl-x. Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding bcl-x are preferred. Methods of using these compounds for modulation of bcl-x expression and for treatment of diseases associated with expression of bcl-x are also provided.
Inventors
- 👤 C. Frank Bennett
- 👤 Nicholas M. Dean
- 👤 Brett P. Monia
- 👤 Brian J. Nickoloff
- 👤 QingQing Zhang
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 14:23
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/11; C12N15/113; C12N15/1135; A; A61; A61K; A61K38/00; C12N2310/00; C12N2310/10; C12N2310/11; C12N2310/30; C12N2310/31; C12N2310/315; C12N2310/318; C12N2310/3181; C12N2310/32; C12N2310/321; C12N2310/323; C12N2310/3233; C12N2310/33; C12N2310/334; C12N2310/3341; C12N2310/34; C12N2310/341; C12N2310/345; C12N2310/346
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
80 words
An antisense compound 8 to 30 nucleotides in length targeted to a nucleic acid molecule encoding a human bcl-x, wherein said antisense compound modulates the expression of human bcl-x, and wherein said antisense compound is an antisense oligonucleotide which comprises at least an 8 nucleobase portion of SEQ ID NO: 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 32, 33, 34, 36, 37, 38, 39, or 40.
Claim 2
Dependent Claim
80 words
An antisense compound 8 to 30 nucleotides in length targeted to a nucleic acid molecule encoding a human bcl-x, wherein said antisense compound modulates the expression of human bcl-x, and wherein said antisense compound is an antisense oligonucleotide which comprises at least an 8 nucleobase portion of SEQ ID NO: 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 32, 33, 34, 36, 37, 38, 39, or 40.
Claim 3
Dependent Claim
18 words
The antisense compound of claim 1 which is an antisense oligonucleotide comprises at least one modified internucleoside linkage.
Claim 4
Dependent Claim
19 words
The antisense compound of claim 2 wherein the modified internucleoside linkage of the antisense oligonucleotide is a phosphorothioate linkage.
Claim 5
Dependent Claim
17 words
The antisense compound of claim 1 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.
Claim 6
Dependent Claim
20 words
The antisense compound of claim 4 wherein the modified sugar moiety of the antisense oligonucleotide is a 2′-O-methoxyethyl sugar moiety.
Claim 7
Dependent Claim
19 words
The antisense compound of claim 5 wherein substantially all sugar moieties of the antisense oligonucleotide are 2′-O-methoxyethyl sugar moieties.
Claim 8
Dependent Claim
16 words
The antisense compound of claim 1 wherein the antisense oligonucleotide comprises at least one modified nucleobase.
Claim 9
Dependent Claim
17 words
The antisense compound of claim 7 wherein the modified nucleobase of the antisense oligonucleotide is a 5-methylcytosine.
Claim 10
Dependent Claim
19 words
The antisense compound of claim 5 wherein each 2′-O-methoxyethyl modified cytosine nucleobase of the antisense oligonucleotide is a 5-methylcytosine.
Claim 11
Dependent Claim
11 words
The antisense compound of claim 1 which is a chimeric oligonucleotide.
Claim 12
Dependent Claim
17 words
A pharmaceutical composition comprising the antisense compound of claim 1 and a pharmaceutically acceptable carrier or diluent.
Claim 13
Dependent Claim
12 words
The pharmaceutical composition of claim 11 further comprising a colloidal dispersion system.
Claim 14
Dependent Claim
12 words
The antisense compound of claim 1 which is targeted 20 to bcl-xl.
Claim 15
Dependent Claim
24 words
The antisense compound of claim 1 which is targeted to a nucleic acid molecule encoding bcl-xl and which preferentially inhibits the expression of bcl-xl.
Claim 16
Dependent Claim
30 words
The antisense compound of claim 14 which is targeted to a region of a nucleic acid molecule encoding bcl-xl which is not found in a nucleic acid molecule encoding bcl-xs.
Claim 17
Dependent Claim
9 words
The antisense compound of claim 14 which promotes apoptosis.
Claim 18
Dependent Claim
26 words
The antisense compound of claim 1 which is targeted to a region of a nucleic acid molecule encoding bcl-xs and which reduces the expression of bcl-xs.
Claim 19
Dependent Claim
9 words
The antisense compound of claim 17 which inhibits apoptosis.
Claim 20
Dependent Claim
19 words
The antisense compound of claim 1 which alters the ratio of bcl-x isoforms expressed by a cell or tissue.
Claim 21
Dependent Claim
15 words
The antisense compound of claim 19 which increases the ratio of bcl-xl to bcl-xs expressed.
Claim 22
Dependent Claim
15 words
The antisense compound of claim 19 which decreases the ratio of bcl-xl to bcl-xs expressed.
Claim 23
Dependent Claim
81 words
An antisense compound 8 to 30 nucleotides in length which is targeted to a bcl-x RNA transcript containing a first and second alternative splice site, which, when contacted with the transcript, reduces the relative frequency of splicing at said second splice site such that the ratio of resulting RNA splice products is altered and wherein said antisense compounds is targeted to at least a portion of the RNA region within 20 nucleotides to the 5′ side of said second splice site.
Claim 24
Dependent Claim
81 words
An antisense compound 8 to 30 nucleotides in length which is targeted to a bcl-x RNA transcript containing a first and second alternative splice site, which, when contacted with the transcript, reduces the relative frequency of splicing at said second splice site such that the ratio of resulting RNA splice products is altered and wherein said antisense compounds is targeted to at least a portion of the RNA region within 20 nucleotides to the 5′ side of said second splice site.
Claim 25
Dependent Claim
11 words
The antisense compound of claim 22 which is an antisense oligonucleotide.
Claim 26
Dependent Claim
17 words
The antisense compound of claim 23 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.
Claim 27
Dependent Claim
20 words
The antisense compound of claim 24 wherein the modified sugar moiety of the antisense oligonucleotide is a 2′-O-methoxyethyl sugar moiety.
Claim 28
Dependent Claim
19 words
The antisense compound of claim 25 wherein substantially all sugar moieties of the antisense oligonucleotide are 2′-O-methoxyethyl sugar moieties.
Claim 29
Dependent Claim
41 words
An antisense compound which alters splicing of an RNA encoding human bcl-x, such that the ratio of bcl-xs to bcl-xl is altered, and which is targeted to nucleotides 664 to 698 of SEQ ID NO:1, a nucleic acid encoding human bcl-x.
Claim 30
Dependent Claim
41 words
An antisense compound which alters splicing of an RNA encoding human bcl-x, such that the ratio of bcl-xs to bcl-xl is altered, and which is targeted to nucleotides 664 to 698 of SEQ ID NO:1, a nucleic acid encoding human bcl-x.
Claim 31
Dependent Claim
11 words
The antisense compound of claim 27 which is an antisense oligonucleotide.
Claim 32
Dependent Claim
17 words
The antisense compound of claim 28 wherein the antisense oligonucleotide comprises at least one 2′-O-methoxyethyl sugar moiety.
Claim 33
Dependent Claim
19 words
The antisense compound of claim 29 wherein substantially all sugar moieties of the antisense oligonucleotide are 2′-O-methoxyethyl sugar moieties.
Claim 34
Dependent Claim
10 words
An antisense oligonucleotide comprising SEQ ID No:33, 34 or 46.
Claim 35
Dependent Claim
10 words
An antisense oligonucleotide comprising SEQ ID No:33, 34 or 46.
Claim 36
Dependent Claim
35 words
A method of inhibiting the expression of bcl-x in human cells or tissues in vitro comprising contacting said cells or tissues with the antisense compound of claim 1 so that expression of bcl-x is inhibited.
Claim 37
Dependent Claim
41 words
A method of altering the ratio of the isoforms of bcl-x in human cells or tissues in vitro comprising contacting said cells or tissues with the antisense compound of claim 1 so that the ratio of the bcl-x isoforms is altered.
Claim 38
Dependent Claim
16 words
The pharmaceutical composition of claim 11 further comprising a chemotherapeutic agent for the treatment of cancer.
Claim 39
Dependent Claim
19 words
The antisense compound of claim 2 wherein the modified internucleoside linkage of the antisense oligonucleotide is a morpholino linkage.
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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) | 2004-01-09 | 2004-07-10 | 2005-01-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2008-01-09 | 2008-07-10 | 2009-01-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2012-01-09 | 2012-07-10 | 2013-01-09 | $7700.00 | Window Closed / Lapsed |