US5583034A
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Enhancement of adoptosis using antisense oligonucleotides
Assignee: La Jolla Institute For Allergy & Immunology
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Filing: 1994-02-22
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Granted: 1996-12-10
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Expires: 2014-02-22
Abstract
Abstract A method is disclosed for enhancement of the efficacy of therapeutic treatment for inducing cell death in a cell having an anti-apoptotic gene by the enhancement of apoptosis. An antisense oligonucleotide is disclosed which hybridizes with the nucleic acid sequence of the anti-apoptotic gene. The oligonucleotide is administered to the cell in an amount sufficient to inhibit expression of the gene, thus rendering the cell susceptible to induction of apoptosis, and consequently achieving higher efficacy of therapeutic treatment.
Inventors
- 👤 Douglas R. Green
- 👤 Thomas G. Cotter
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 13:30
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/11; C12N15/113; C12N15/1135; A; A61; A61K; A61K38/00; C12N2310/00; C12N2310/30; C12N2310/31; C12N2310/312; C12N2310/3125; C12N2310/315
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
11 words
An antisense oligonucleotide having the nucleotide sequence 5'-GCCCACCGGGTCCACCAT-3' (SEQ ID NO:3).
Claim 2
Dependent Claim
11 words
An antisense oligonucleotide having the nucleotide sequence 5'-GCCCACCGGGTCCACCAT-3' (SEQ ID NO:3).
Claim 3
Dependent Claim
11 words
The antisense oligonucleotide of claim 1 which is a DNA sequence.
Claim 4
Dependent Claim
10 words
The antisense oligonucleotide of claim 1 which is chemically modified.
Claim 5
Dependent Claim
16 words
The antisense oligonucleotide of claim 3 which comprises at least one methylphosphonate or phosphorothioate internucleotide linkage.
Claim 6
Independent Claim
74 words
A method for inducing death in a cell having a gene encoding the bcr-abl polypeptide comprising the steps of: a) administering to the cell in vitro an antisense oligonucleotide having the nucleotide sequence selected from the group consisting of 5'-GCCCACCGGGTCCACCAT-3' (SEQ ID NO:3) and 5'-TACTGGCCGCTGAAGGGC-3' (SEQ ID NO:4) in an amount sufficient to inhibit the expression of the bcr-abl gene; and b) exposing the cell to a chemical or physical means for inducing apoptosis.
Claim 7
Independent Claim
74 words
A method for inducing death in a cell having a gene encoding the bcr-abl polypeptide comprising the steps of: a) administering to the cell in vitro an antisense oligonucleotide having the nucleotide sequence selected from the group consisting of 5'-GCCCACCGGGTCCACCAT-3' (SEQ ID NO:3) and 5'-TACTGGCCGCTGAAGGGC-3' (SEQ ID NO:4) in an amount sufficient to inhibit the expression of the bcr-abl gene; and b) exposing the cell to a chemical or physical means for inducing apoptosis.
Claim 8
Dependent Claim
11 words
The method of claim 5, wherein the antisense oligonucleotide is DNA.
Claim 9
Dependent Claim
12 words
The method of claim 5 wherein the antisense oligonucleotide is chemically modified.
Claim 10
Dependent Claim
18 words
The method of claim 7 wherein the antisense oligonucleotide comprises at least one methylphosphonate or phosphorothioate internucleotide linkage.
Claim 11
Dependent Claim
19 words
The method of claim 5, wherein the cell is a chronic myelogenous leukemia cell having a translocated bcr-abl gene.
Claim 12
Dependent Claim
20 words
The method of claim 5, wherein the means for inducing apoptosis comprises exposing the cells to a chemotherapeutic apoptotic agent.
Claim 13
Dependent Claim
24 words
The method of claim 10, wherein the chemotherapeutic apoptotic agent is selected from the group consisting of actinomycin D, etoposide, cycloheximide, VM-26, and camptothecin.
Claim 14
Dependent Claim
15 words
The method of claim 5, wherein the means for inducing apoptosis is a physical treatment.
Claim 15
Dependent Claim
24 words
The method of claim 12, wherein the physical treatment is selected from the group consisting of γ-radiation, ultraviolet light, heat shock and cold shock.
Claim 16
Independent Claim
81 words
A method of identifying an agent which induces apoptosis in a cell having a gene encoding the bcr-abl polypeptide comprising the steps of: a) contacting the cell in vitro with an antisense oligonucleotide having the nucleotide sequence selected from the group consisting of 5'-GCCCACCGGGTCCACCAT-3' (SEQ ID NO:3) and 5'-TACTGGCCGCTGAAGGGC-3' (SEQ ID NO:4) in an amount sufficient to inhibit the expression of the bcr-abl gene; b) contacting the cell with a putative apoptotic agent; and c) observing the effect on the cell.
Claim 17
Independent Claim
81 words
A method of identifying an agent which induces apoptosis in a cell having a gene encoding the bcr-abl polypeptide comprising the steps of: a) contacting the cell in vitro with an antisense oligonucleotide having the nucleotide sequence selected from the group consisting of 5'-GCCCACCGGGTCCACCAT-3' (SEQ ID NO:3) and 5'-TACTGGCCGCTGAAGGGC-3' (SEQ ID NO:4) in an amount sufficient to inhibit the expression of the bcr-abl gene; b) contacting the cell with a putative apoptotic agent; and c) observing the effect on the cell.
References Cited (Backward Citations)
WO1992022303A1
Cited
US5360893A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-12-10 | 2000-06-10 | 2000-12-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-12-10 | 2004-06-10 | 2004-12-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-12-10 | 2008-06-10 | 2008-12-10 | $7700.00 | Window Closed / Lapsed |